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Melanoma: HELP
Articles by Eve Maubec
Based on 24 articles published since 2008
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Between 2008 and 2019, E. Maubec wrote the following 24 articles about Melanoma.
 
+ Citations + Abstracts
1 Guideline Guidelines of the French Society of Otorhinolaryngology (SFORL), short version. Extension assessment and principles of resection in cutaneous head and neck tumors. 2014

Anonymous4420813 / Durbec, M / Couloigner, V / Tronche, S / Albert, S / Kanitakis, J / Ltaief Boudrigua, A / Malard, O / Maubec, E / Mourrain Langlois, E / Navailles, B / Peuvrel, L / Phulpin, B / Thimonier, J-C / Disant, F / Dolivet, G. ·Service d'ORL, hôpital Édouard-Herriot, 5, place d'Arsonval, 69003 Lyon, France. Electronic address: mickael.durbec@chu-lyon.fr. · Société française d'ORL & CCF, 26, rue Lalo, 75116 Paris, France. · Service d'ORL, hôpital Bichat, AP-HP, 46, rue Henri-Huchard, 75018 Paris, France. · Service de dermatologie, hôpital Édouard-Herriot, 5, place d'Arsonval, 69003 Lyon, France. · Service de radiologie, hôpital Édouard-Herriot, 5, place d'Arsonval, 69003 Lyon, France. · Service d'ORL, Hôtel-Dieu, 1, place Alexis-Ricordeau, 44093 Nantes cedex 1, France. · Service de dermatologie, hôpital Saint-Louis, 1, avenue Claude-Vellefaux, 75010 Paris, France. · Service de radiologie, Hôtel-Dieu, 1, place Alexis-Ricordeau, 44093 Nantes cedex 1, France. · Service d'ORL, centre hospitalier de Valence, 179, avenue du Maréchal-Juin, 26000 Valence, France. · Service d'onco-dermatologie, Hôtel-Dieu, 1, place Alexis-Ricordeau, 44093 Nantes cedex 1, France. · Institut de cancérologie de Lorraine, 6, avenue de Bourgogne, 54519 Vandœuvre-lès-Nancy, France. · Service d'ORL, hôpital Édouard-Herriot, 5, place d'Arsonval, 69003 Lyon, France. · Service d'ORL, département de chirurgie oncologique, institut de cancérologie de Lorraine, 6, avenue de Bourgogne, 54519 Vandœuvre-lès-Nancy, France. ·Eur Ann Otorhinolaryngol Head Neck Dis · Pubmed #25456243.

ABSTRACT: Cutaneous head and neck tumors mainly comprise malignant melanoma, squamous cell carcinoma, trichoblastic carcinoma, Merkel cell carcinoma, adnexal carcinoma, dermatofibrosarcoma protuberans, sclerodermiform basalioma and angiosarcoma. Adapted management requires an experienced team with good knowledge of the various parameters relating to health status, histology, location and extension: risk factors for aggression, extension assessment, resection margin requirements, indications for specific procedures, such as lateral temporal bone resection, orbital exenteration, resection of the calvarium and meningeal envelopes, neck dissection and muscle resection.

2 Clinical Trial Metformin monotherapy in melanoma: a pilot, open-label, prospective, and multicentric study indicates no benefit. 2017

Montaudié, Henri / Cerezo, Michael / Bahadoran, Philippe / Roger, Coralie / Passeron, Thierry / Machet, Laurent / Arnault, Jean-Philippe / Verneuil, Laurence / Maubec, Eve / Aubin, François / Granel, Florence / Giacchero, Damien / Hofman, Véronique / Lacour, Jean-Philippe / Maryline, Allegra / Ballotti, Robert / Rocchi, Stéphane. ·Department of Dermatology, University Hospital of Nice, Nice, France. · Team 12, Centre Méditerranéen de Médecine Moléculaire, INSERM, U1065, Nice, France. · Team 1, Centre Méditerranéen de Médecine Moléculaire, INSERM, U1065, Nice, France. · Department of Dermatology, Clinical Research Center, Archet Hospital, Nice, France. · Department of Clinical Research and Innovation, University Hospital of Nice, Nice, France. · Department of Dermatology, CHRU de Tours, University Francois Rabelais of Tours, Tours, France. · Department of Dermatology, University Hospital of Amiens, Amiens, France. · Department of Dermatology, University Hospital of Caen, Caen, France. · Department of Dermatology, University Hospital of Paris, Hospital Bichat, Nice, France. · Department of Dermatology, University Hospital of Besançon, Besançon, France. · Department of Dermatology, University Hospital of Nancy, Nancy, France. · Department of Oncology, Antoine Lacassagne Cancer Center, University of Nice-Sophia, Nice, France. · Laboratory of Clinical and Experimental Pathology and Human Biobank, Nice University Hospital, Nice, France. · Faculty of Medicine, INSERM 1081 Team 3 IRCAN, University of Nice Sophia Antipolis, Nice, France. ·Pigment Cell Melanoma Res · Pubmed #28122176.

ABSTRACT: -- No abstract --

3 Clinical Trial First-in-human phase I study of the DNA-repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma. 2016

Le Tourneau, C / Dreno, B / Kirova, Y / Grob, J J / Jouary, T / Dutriaux, C / Thomas, L / Lebbé, C / Mortier, L / Saiag, P / Avril, M F / Maubec, E / Joly, P / Bey, P / Cosset, J M / Sun, J S / Asselain, B / Devun, F / Marty, M E / Dutreix, M. ·Department of Medical Oncology, Institut Curie, Paris & Saint-Cloud 75005, France. · EA7285, Versailles-Saint-Quentin-en-Yvelines University, Versailles 78000, France. · CHU de Nantes-Hôtel Dieu, Nantes 44093, France. · Radiotherapy Department, Institut Curie, Paris 75005, France. · La Timone Hospital-APHM, Aix-Marseille University, Marseille 13385, France. · Dermatology department, Saint-André Hospital, CHU de Bordeaux, Bordeaux 33000, France. · Lyon Sud Hospital Center, Lyon 1 University, Pierre Benite 69495, France. · Saint-Louis Hospital, APHP, Paris 75010, France. · Dermatology department, CHRU of Lille, Lille 59037, France. · Ambroise Paré Hospital, Boulogne Billancourt 92104, France. · Cochin hospital, APHP, Paris 75014, France. · Bichat Hospital, Paris 75877, France. · CHU Rouen, Charles-Nicolle, Rouen 76000, France. · Institut Curie, Paris 75005, France. · DNA Therapeutics, Evry 91058, France. · Department of Biostatistics, Institut Curie, Paris 75005, France. · Institut Curie, Orsay 91405, France. · CNRS-UMR3347, INSERM-U1021, Paris-Sud University, Orsay 91405, France. ·Br J Cancer · Pubmed #27140316.

ABSTRACT: BACKGROUND: DT01 is a DNA-repair inhibitor preventing recruitment of DNA-repair enzymes at damage sites. Safety, pharmacokinetics and preliminary efficacy through intratumoural and peritumoural injections of DT01 were evaluated in combination with radiotherapy in a first-in-human phase I trial in patients with unresectable skin metastases from melanoma. METHODS: Twenty-three patients were included and received radiotherapy (30 Gy in 10 sessions) on all selected tumour lesions, comprising of two lesions injected with DT01 three times a week during the 2 weeks of radiotherapy. DT01 dose levels of 16, 32, 48, 64 and 96 mg were used, in a 3+3 dose escalation design, with an expansion cohort at 96 mg. RESULTS: The median follow-up was 180 days. All patients were evaluable for safety and pharmacokinetics. No dose-limiting toxicity was observed and the maximum-tolerated dose was not reached. Most frequent adverse events were reversible grades 1 and 2 injection site reactions. Pharmacokinetic analyses demonstrated a systemic passage of DT01. Twenty-one patients were evaluable for efficacy on 76 lesions. Objective response was observed in 45 lesions (59%), including 23 complete responses (30%). CONCLUSIONS: Intratumoural and peritumoural DT01 in combination with radiotherapy is safe and pharmacokinetic analyses suggest a systemic passage of DT01.

4 Clinical Trial Characterization of the Microenvironment in Positive and Negative Sentinel Lymph Nodes from Melanoma Patients. 2015

Messaoudene, Meriem / Périer, Aurélie / Fregni, Giulia / Neves, Emmanuelle / Zitvogel, Laurence / Cremer, Isabelle / Chanal, Johan / Sastre-Garau, Xavier / Deschamps, Lydia / Marinho, Eduardo / Larousserie, Frederique / Maubec, Eve / Avril, Marie-Françoise / Caignard, Anne. ·INSERMU1160, Institut Universitaire d'Hématologie, Hôpital Saint Louis, 1 Avenue Claude Vellefaux, 75010, Paris, France. · U1015 INSERM-CIC, Institut Gustave Roussy, Villejuif, France. · Centre de Recherche des Cordeliers, 15, rue de l'école de Médecine, 75006, Paris, France. · APHP, Department of Dermatology, Hospital Cochin, University Paris Descartes, Paris, France. · Biopathology Department, Institut Curie, Rue d'Ulm, Paris, France. · APHP, Department of Dermatology and Department of Pathology, Hospital Bichat, University Paris Diderot, Hospital Bichat, 75018, Paris, France. · APHP, Department of Pathology, Hospital Cochin, University Paris Descartes, Paris, France. ·PLoS One · Pubmed #26218530.

ABSTRACT: Melanomas are aggressive skin tumors characterized by high metastatic potential. Our previous results indicate that Natural Killer (NK) cells may control growth of melanoma. The main defect of blood NK cells was a decreased expression of activating NCR1/NKp46 receptor and a positive correlation of NKp46 expression with disease outcome in stage IV melanoma patients was found. In addition, in stage III melanoma patients, we identified a new subset of mature NK cells in macro-metastatic Lymph nodes (LN). In the present studies, we evaluated the numbers of NK cells infiltrating primary cutaneous melanoma and analyzed immune cell subsets in a series of sentinel lymph nodes (SLN). First, we show that NKp46+ NK cells infiltrate primary cutaneous melanoma. Their numbers were related to age of patients and not to Breslow thickness. Then, a series of patients with tumor-negative or -positive sentinel lymph nodes matched for Breslow thickness of the cutaneous melanoma was constituted. We investigated the distribution of macrophages (CD68), endothelial cells, NK cells, granzyme B positive (GrzB+) cells and CD8+ T cells in the SLN. Negative SLN (SLN-) were characterized by frequent adipose involution and follicular hyperplasia compared to positive SLN (SLN+). High densities of macrophages and endothelial cells (CD34), prominent in SLN+, infiltrate SLN and may reflect a tumor favorable microenvironment. Few but similar numbers of NK and GrzB+ cells were found in SLN- and SLN+: NK cells and GrzB+ cells were not correlated. Numerous CD8+ T cells infiltrated SLN with a trend for higher numbers in SLN-. Moreover, CD8+ T cells and GrzB+ cells correlated in SLN- not in SLN+. We also observed that the numbers of CD8+ T cells negatively correlated with endothelial cells in SLN-. The numbers of NK, GrzB+ or CD8+ T cells had no significant impact on overall survival. However, we found that the 5 year-relapse rate was higher in SLN with higher numbers of NK cells.

5 Article Relevance of serum biomarkers associated with melanoma during follow-up of anti-CTLA-4 immunotherapy. 2016

Felix, Joana / Cassinat, Bruno / Porcher, Raphael / Schlageter, Marie-Hélène / Maubec, Eve / Pages, Cécile / Baroudjian, Barouyr / Homyrda, Laurence / Boukouaci, Wahid / Tamouza, Ryad / Bagot, Martine / Caignard, Anne / Toubert, Antoine / Lebbé, Céleste / Moins-Teisserenc, Hélène. ·INSERM UMR-1160, Institut Universitaire d'Hématologie, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Paris, France. · Laboratoire de Biologie Cellulaire, AP-HP, Hopital Saint-Louis, Paris, France; Inserm UMRS-1131, Institut Universitaire d'Hématologie, Paris, France. · Centre d'Epidémiologie Clinique, Hôtel-Dieu, AP-HP, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; INSERM, UMR 1153, Centre de Recherche Epidémiologie et Statistique (CRESS), Paris, France. · Laboratoire de Biologie Cellulaire, AP-HP, Hopital Saint-Louis, Paris, France. · Service de Dermatologie, Hôpital Xavier Bichat, AP-HP, Paris, France. · Service de Dermatologie, AP-HP, Hôpital Saint Louis, Paris, France. · Laboratoire d'Immunologie-Histocompatibilité, AP-HP, Hôpital Saint Louis, Paris, France. · Université Paris Diderot, Sorbonne Paris Cité, Paris, France; Service de Dermatologie, AP-HP, Hôpital Saint Louis, Paris, France; INSERM UMR-976, Hôpital Saint-Louis, Paris, France. · INSERM UMR-1160, Institut Universitaire d'Hématologie, Paris, France. · INSERM UMR-1160, Institut Universitaire d'Hématologie, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Paris, France. Electronic address: helene.moins@univ-paris-diderot.fr. ·Int Immunopharmacol · Pubmed #27728898.

ABSTRACT: Metastatic melanoma is a rapidly spreading cancer whose prognosis remains poor although important therapy advances in recent years. Ipilimumab, an anti-CTLA-4 immunotherapy used in advanced melanoma, is an effective immunotherapy alone or combined with other agents but with few predictive biomarkers of response. Here, we sought to analyze the potential of S100B, MIA, soluble MICA, anti-MICA antibodies and LDH as serum biomarkers of response and survival in a cohort of 77 advanced melanoma patients subjected to ipilimumab. Lower levels of S100B, and LDH at baseline and at weeks 3 and 6 correlated to a better response and survival. After multivariate analysis LDH maintained its independence at baseline and week 6, whereas S100B might be a useful tool for anti-CTLA-4 treatment monitoring after the first two doses of ipilimumab (W6). In addition, higher sMICA serum levels at baseline were associated with less frequency of irAEs.

6 Article A comprehensive genome-wide analysis of melanoma Breslow thickness identifies interaction between CDC42 and SCIN genetic variants. 2016

Vaysse, Amaury / Fang, Shenying / Brossard, Myriam / Wei, Qingyi / Chen, Wei V / Mohamdi, Hamida / Vincent-Fetita, Lynda / Margaritte-Jeannin, Patricia / Lavielle, Nolwenn / Maubec, Eve / Lathrop, Mark / Avril, Marie-Françoise / Amos, Christopher I / Lee, Jeffrey E / Demenais, Florence. ·INSERM, Genetic Variation and Human Diseases Unit, UMR-946, Paris, France. · Université Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Université Paris Diderot, Paris, France. · Department of Surgical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX. · Duke Cancer Institute, Duke University Medical Center and Department of Medicine, Duke University School of Medicine, Durham, NC. · Laboratory Informatics System, Department of Clinical Applications & Support, the University of Texas M. D. Anderson Cancer Center, Houston, TX. · AP-HP, Hôpital Cochin Et Université Paris Descartes, Paris, France. · AP-HP, Service De Dermatologie, Hôpital Avicenne, t Université Paris 13, Bobigny, France. · McGill University and Genome Quebec Innovation Centre, Montreal, Quebec, Canada. · Department of Community and Family Medicine, Geisel College of Medicine, Dartmouth College, Hanover, NH. ·Int J Cancer · Pubmed #27347659.

ABSTRACT: Breslow thickness (BT) is a major prognostic factor of cutaneous melanoma (CM), the most fatal skin cancer. The genetic component of BT has only been explored by candidate gene studies with inconsistent results. Our objective was to uncover the genetic factors underlying BT using an hypothesis-free genome-wide approach. Our analysis strategy integrated a genome-wide association study (GWAS) of single nucleotide polymorphisms (SNPs) for BT followed by pathway analysis of GWAS outcomes using the gene-set enrichment analysis (GSEA) method and epistasis analysis within BT-associated pathways. This strategy was applied to two large CM datasets with Hapmap3-imputed SNP data: the French MELARISK study for discovery (966 cases) and the MD Anderson Cancer Center study (1,546 cases) for replication. While no marginal effect of individual SNPs was revealed through GWAS, three pathways, defined by gene ontology (GO) categories were significantly enriched in genes associated with BT (false discovery rate ≤5% in both studies): hormone activity, cytokine activity and myeloid cell differentiation. Epistasis analysis, within each significant GO, identified a statistically significant interaction between CDC42 and SCIN SNPs (pmeta-int =2.2 × 10(-6) , which met the overall multiple-testing corrected threshold of 2.5 × 10(-6) ). These two SNPs (and proxies) are strongly associated with CDC42 and SCIN gene expression levels and map to regulatory elements in skin cells. This interaction has important biological relevance since CDC42 and SCIN proteins have opposite effects in actin cytoskeleton organization and dynamics, a key mechanism underlying melanoma cell migration and invasion.

7 Article Vemurafenib pharmacokinetics and its correlation with efficacy and safety in outpatients with advanced BRAF-mutated melanoma. 2016

Kramkimel, N / Thomas-Schoemann, A / Sakji, L / Golmard, Jl / Noe, G / Regnier-Rosencher, E / Chapuis, N / Maubec, E / Vidal, M / Avril, Mf / Goldwasser, F / Mortier, L / Dupin, N / Blanchet, B. ·Assistance Publique Hôpitaux de Paris, Département de Dermatologie, Hôpital Cochin, Paris, France. · Centre d'étude et de recours sur les inhibiteurs de l'angiogénèse (CERIA), Paris, France. · Assistance Publique Hôpitaux de Paris, Unité Fonctionnelle de Pharmacocinétique et Pharmacochimie, Hôpital Cochin, 27 rue du Faubourg Saint Jacques, 75014, Paris, France. · UMR8638 CNRS, UFR de Pharmacie, Université Paris Descartes, PRES Sorbonne Paris Cité, Paris, France. · CHRU de Lille, Service de Dermatologie, Paris, France. · Assistance Publique Hôpitaux de Paris, Département de Biostatistiques, Hôpital Pitié-Salpêtrière, Paris, France. · Assistance Publique Hôpitaux de Paris, Service d'Hématologie biologique, Hôpital Cochin, Paris, France. · Assistance Publique Hôpitaux de Paris, Département de Dermatologie, Hôpital Bichat, Paris, France. · Institut Cochin, Institut National de la Sante et de la Recherche Médicale (INSERM) U1016, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Faculté de médecine, Université Paris Descartes, PRES Sorbonne Paris Cité, Paris, France. · Assistance Publique Hôpitaux de Paris, Service de Cancérologie médicale, Hôpital Cochin, Paris, France. · INSERM U 837, Faculté de Médecine, Université de Lille II, Lille, France. · Centre d'étude et de recours sur les inhibiteurs de l'angiogénèse (CERIA), Paris, France. benoit.blanchet@cch.aphp.fr. · Assistance Publique Hôpitaux de Paris, Unité Fonctionnelle de Pharmacocinétique et Pharmacochimie, Hôpital Cochin, 27 rue du Faubourg Saint Jacques, 75014, Paris, France. benoit.blanchet@cch.aphp.fr. ·Target Oncol · Pubmed #26208946.

ABSTRACT: Vemurafenib is a BRAF kinase inhibitor approved for first-line treatment of metastatic BRAF (V600) -mutant melanoma. However, data on the pharmacokinetic/pharmacodynamic (PK/PD) relationship are lacking. The aim of this prospective, multicenter study was to explore the PK/PD relationship for vemurafenib in outpatients with advanced BRAF-mutated melanoma. Fifty-nine patients treated with single-agent vemurafenib were prospectively analyzed. Vemurafenib plasma concentration (n = 159) was measured at days 15, 30, 60, and 90 after treatment initiation. Clinical and biological determinants (including plasma vemurafenib concentration) for efficacy and safety were assessed using Cox's model and multivariate stepwise logistic regression. Median progression-free survival (PFS) and overall survival were 5.0 (95 % confidence interval [95 % CI] 2.0-6.0) and 11.0 (95% CI 7.0-16.0) months, respectively. Twenty-nine patients (49 %) experienced any grade ≥3 toxicity and the most frequent grade ≥2 toxicity was skin rash (37 %). Severe toxicities led to definitive discontinuation in seven patients (12 %). Grade ≥2 skin rash was not statistically associated with better objective response at day 60 (p = 0.06) and longer PFS (hazard ratio 0.47; 95 % CI 0.21-1.08; p = 0.075). Grade ≥2 skin rash was statistically increased in patients with ECOG  ≥ 1 (odds ratio 4.67; 95 % CI 1.39-15.70; p = 0.012). Vemurafenib concentration below 40.4 mg/L at day 15 was significantly associated with a shorter PFS (1.5 [0.5-5.5] vs. 4.5 [2-undetermined] months, p = 0.029). Finally, vemurafenib concentration was significantly greater in patients developing grade ≥2 rash (61.7 ± 25.0 vs. 36.3 ± 17.9 mg/L, p < 0.0001). These results suggest that early plasma drug monitoring may help identify outpatients at high risk of non-response or grade ≥ 2 skin rash.

8 Article Integrated pathway and epistasis analysis reveals interactive effect of genetic variants at TERF1 and AFAP1L2 loci on melanoma risk. 2015

Brossard, Myriam / Fang, Shenying / Vaysse, Amaury / Wei, Qingyi / Chen, Wei V / Mohamdi, Hamida / Maubec, Eve / Lavielle, Nolwenn / Galan, Pilar / Lathrop, Mark / Avril, Marie-Françoise / Lee, Jeffrey E / Amos, Christopher I / Demenais, Florence. ·INSERM, Genetic Variation and Human Diseases Unit, UMR-946, Paris, France. · Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Duke Cancer Institute, Duke University Medical center and Department of Medicine, Duke University School of Medicine, Durham, NC, USA. · Laboratory Informatics System, Department of Clinical Applications & Support, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA. · AP-HP (Assistance Publique-Hôpitaux de Paris), Hôpital Bichat, Service de Dermatologie, Université Paris Diderot, Paris, France. · INSERM, UMR U557; Institut national de la Recherche Agronomique,U1125; Conservatoire national des arts et métiers, Centre de Recherche en Nutrition Humaine, Ile de France, Bobigny, France. · McGill University and Genome Quebec Innovation Centre, Montreal, Quebec, Canada. · AP-HP, Hôpital Cochin et Université Paris Descartes, Paris, France. · Department of Community and Family Medicine, Geisel College of Medicine, Dartmouth College, Hanover, New Hampshire, USA. ·Int J Cancer · Pubmed #25892537.

ABSTRACT: Genome-wide association studies (GWASs) have characterized 13 loci associated with melanoma, which only account for a small part of melanoma risk. To identify new genes with too small an effect to be detected individually but which collectively influence melanoma risk and/or show interactive effects, we used a two-step analysis strategy including pathway analysis of genome-wide SNP data, in a first step, and epistasis analysis within significant pathways, in a second step. Pathway analysis, using the gene-set enrichment analysis (GSEA) approach and the gene ontology (GO) database, was applied to the outcomes of MELARISK (3,976 subjects) and MDACC (2,827 subjects) GWASs. Cross-gene SNP-SNP interaction analysis within melanoma-associated GOs was performed using the INTERSNP software. Five GO categories were significantly enriched in genes associated with melanoma (false discovery rate ≤ 5% in both studies): response to light stimulus, regulation of mitotic cell cycle, induction of programmed cell death, cytokine activity and oxidative phosphorylation. Epistasis analysis, within each of the five significant GOs, showed significant evidence for interaction for one SNP pair at TERF1 and AFAP1L2 loci (pmeta-int  = 2.0 × 10(-7) , which met both the pathway and overall multiple-testing corrected thresholds that are equal to 9.8 × 10(-7) and 2.0 × 10(-7) , respectively) and suggestive evidence for another pair involving correlated SNPs at the same loci (pmeta-int  = 3.6 × 10(-6) ). This interaction has important biological relevance given the key role of TERF1 in telomere biology and the reported physical interaction between TERF1 and AFAP1L2 proteins. This finding brings a novel piece of evidence for the emerging role of telomere dysfunction into melanoma development.

9 Article [Recommendations for genetic testing and management of individuals genetically at-risk of cutaneous melanoma]. 2015

Avril, M-F / Bahadoran, P / Cabaret, O / Caron, O / de la Fouchardière, A / Demenais, F / Desjardins, L / Frébourg, T / Hammel, P / Leccia, M-T / Lesueur, F / Mahé, E / Martin, L / Maubec, E / Remenieras, A / Richard, S / Robert, C / Soufir, N / Stoppa-Lyonnet, D / Thomas, L / Vabres, P / Bressac-de Paillerets, B. ·Service de dermatologie, groupe hospitalier Cochin-Saint-Vincent-de-Paul, AP-HP, pavillon Tarnier, 89, rue d'Assas, 75006 Paris, France. · Inserm U895, service de dermatologie, hôpital Archet 2, CHU, 151, route Saint-Antoine-Ginestiere, BP 79, 06200 Nice cedex 3, France. · Service de génétique, département de biologie et pathologie médicales, Gustave-Roussy, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France. · Consultation d'oncogénétique, Gustave-Roussy, 114, rue Édouard-Vaillant, 94805 Villejuif, France. · Département de biopathologie, centre Léon-Bérard, 28, rue Laennec, 69008 Lyon, France. · Inserm, UMR946, variabilité génétique et maladies humaines, fondation Jean-Dausset, CEPH, 27, rue Juliette-Dodu, 75010 Paris, France. · Service d'ophtalmologie, institut Curie, 26, rue d'Ulm, 75231 Paris cedex 05, France. · Inserm U1079, service de génétique, CHU de Rouen, IRIB, faculté de médecine et de pharmacie, 22, boulevard Gambetta, 76183 Rouen cedex, France. · Service de gastro-entérologie-pancréatologie, hôpital Beaujon, AP-HP, 100, boulevard du Général-Leclerc, 92118 Clichy cedex, France. · Service de dermatologie, CHU Michallon, BP 217, 38043 Grenoble cedex 9, France. · Inserm U900, équipe épidémiologie génétique des cancers, institut Curie, 26, rue d'Ulm, 75248 Paris cedex 05, France. · Service de dermatologie, centre hospitalier Victor-Dupouy, 69, rue du Lieutenant-Colonel-Prud'hon, 95107 Argenteuil cedex, France. · Service de dermatologie, CHU d'Angers, université d'Angers, 4, rue Larrey, 49933 Angers cedex 9, France. · Inserm, UMR946, variabilité génétique et maladies humaines, fondation Jean-Dausset, CEPH, 27, rue Juliette-Dodu, 75010 Paris, France; Service de dermatologie, hôpital Bichat, AP-HP, 46, rue Henri-Huchard, 75018 Paris, France. · Département d'oncologie génétique, institut Paoli-Calmettes, 232, boulevard Saint-Marguerite, 13273 Marseille cedex 9, France. · Service d'urologie, hôpital Bicêtre, Centre expert national cancers rares INCa PREDIR, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France. · Service de dermatologie, Gustave-Roussy, 114, rue Édouard-Vaillant, 94805 Villejuif, France. · Inserm U976, laboratoire de génétique moléculaire, unité fonctionnelle de génétique, hôpital Xavier-Bichat-Claude-Bernard, AP-HP, Paris 7 université, 75018 Paris, France. · Inserm U830, service de génétique, département de biologie des tumeurs, institut Curie, 26, rue d'Ulm, 75231 Paris cedex 05, France. · Service de dermatologie, centre hospitalier Lyon Sud, université Lyon 1, 165, chemin du Grand-Revoyet, 69495 Pierre-Bénite cedex, France. · Service de dermatologie, CHU de Dijon, BP 77908, 21079 Dijon cedex, France. · Service de génétique, département de biologie et pathologie médicales, Gustave-Roussy, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France. Electronic address: brigitte.bressac@gustaveroussy.fr. ·Ann Dermatol Venereol · Pubmed #25600792.

ABSTRACT: Cutaneous melanoma is a multifactorial disease resulting from both environmental and genetic factors. Five susceptibility genes have been identified over the past years, comprising high-risk susceptibility genes (CDKN2A, CDK4, and BAP1 genes) and intermediate-risk susceptibility genes (MITF, and MC1R genes). The aim of this expert consensus was to define clinical contexts justifying genetic analyses, to describe the conduct of these analyses, and to propose surveillance recommendations. Given the regulatory constraints, it is recommended that dermatologists work in tandem with a geneticist. Genetic analysis may be prescribed when at least two episodes of histologically proven invasive cutaneous melanoma have been diagnosed before the age of 75 years in two 1st or 2nd degree relatives or in the same individual. The occurrence in the same individual or in a relative of invasive cutaneous melanoma with ocular melanoma, pancreatic cancer, renal cancer, mesothelioma or a central nervous system tumour are also indications for genetic testing. Management is based upon properly managed photoprotection and dermatological monitoring according to genetic status. Finally, depending on the mutated gene and the familial history, associated tumour risks require specific management (e.g. ocular melanoma, pancreatic cancer). Due to the rapid progress in genetics, these recommendations will need to be updated regularly.

10 Article Mature cytotoxic CD56(bright)/CD16(+) natural killer cells can infiltrate lymph nodes adjacent to metastatic melanoma. 2014

Messaoudene, Meriem / Fregni, Giulia / Fourmentraux-Neves, Emmanuelle / Chanal, Johan / Maubec, Eve / Mazouz-Dorval, Sarra / Couturaud, Benoit / Girod, Angelique / Sastre-Garau, Xavier / Albert, Sebastien / Guédon, Charles / Deschamps, Lydia / Mitilian, Delphine / Cremer, Isabelle / Jacquelot, Nicolas / Rusakiewicz, Sylvie / Zitvogel, Laurence / Avril, Marie-Francoise / Caignard, Anne. ·Authors' Affiliations: INSERM U1016, CNRS UMR 8104, Institut Cochin; APHP, Department of Dermatology, Hospital Cochin, University Paris Descartes; APHP, Department of Dermatology; APHP, Department of Surgery, Hospital Bichat, University Paris Diderot; Surgery Department, Institut Curie, rue d'Ulm-Paris; Hospital Foch, Suresnes; Centre de Recherche des Cordeliers, 15 rue de l'école de médecine; and INSERM U1015 INSERM, Institut Gustave Roussy, Villejuif, Paris, France. ·Cancer Res · Pubmed #24225017.

ABSTRACT: Melanomas are characterized by high metastatic potential, with regional lymph node representing the most frequent site of early dissemination in this disease. These regional lymph nodes also represent the primary site for differentiation of natural killer (NK) cells. Although blood-derived NK cells can efficiently lyse melanoma cells isolated from metastatic lymph node (M-LN), there has been no study of the properties of the most disease-relevant NK cells isolated from M-LN in patients with melanoma. Here, we report that M-LN contains 0.5% to 11% of CD56(bright) NK cells among CD45(+) hematopoietic cells present and that this cell population surrounds tumor cell clusters in M-LN. This NK cell population was characterized by expression of CD62L, chemokine receptors, and high levels of natural cytotoxicity receptors (NCR), NK group 2 D (NKG2D), and DNAX accessory molecule 1 (DNAM-1). Expression of NCR-NKp30 and NKG2D correlated negatively with percentages of tumor cells in M-LN. Interestingly, M-LN contained a unique subset of mature CD56(bright)CD16(+) NK cells displaying coregulated expression of NCR and NKG2D activating receptors. Ex vivo analyses suggested that M-LN-derived NK cells were inactive but could be activated by appropriate cytokine signals [interleukin (IL)-2 or IL-15], and could lyse metastatic melanoma cells in a highly efficient manner compared with blood-derived NK cells. Taken together, the results offer evidence that adjuvant immunotherapy that targets NK cells in M-LN for activation may improve treatment of patients with sentinel lymph node-positive melanoma.

11 Article Phenotypic and functional characteristics of blood natural killer cells from melanoma patients at different clinical stages. 2013

Fregni, Giulia / Messaoudene, Meriem / Fourmentraux-Neves, Emmanuelle / Mazouz-Dorval, Sarra / Chanal, Johan / Maubec, Eve / Marinho, Eduardo / Scheer-Senyarich, Isabelle / Cremer, Isabelle / Avril, Marie-Françoise / Caignard, Anne. ·Cochin Institute, Institut National de la Sante et de la Recherche Medicale (INSERM) U1016, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, University Paris Descartes, Paris, France. ·PLoS One · Pubmed #24204708.

ABSTRACT: Melanomas are aggressive skin tumors characterized by high metastatic potential. Immunotherapy is a valuable alternative for metastatic melanoma patients resistant to chemotherapy. Natural Killer (NK) cells are efficient anti-tumor cytotoxic effectors. We previously showed that blood NK cells from stage IV metastatic melanoma patients display decreased NK receptors and that chemotherapy modifies the functional status of blood NK cells. To investigate the role of NK cells along melanoma progression, we have here studied NK cells from patients at different stages of the disease. First, we showed that ex vivo NK cells from certain stage III-IV patients displayed low degranulation potential. Using a dynamic label-free assay, we found that immunoselected IL-2 activated blood NK cells from patients efficiently lysed melanoma cells through NKp46 and NKG2D receptors, independently to the clinical stage. Moreover, the ex vivo phenotype of circulating NK cells from 33 patients (stage I to IV) was extensively analyzed. NK cells from patients displayed higher variability in the percentages of Natural Cytotoxicity Receptors (NCR) and Natural Killer Group 2D (NKG2D) receptor expression compared to donor NK cells. The main defect was the decreased expression of NCR1 (NKp46) by NK cells from metastatic patients. Interestingly, we found a positive correlation between the NK cell percentages of NKp46 and the duration of stage IV in melanoma patients. Finally, we showed that NK cells infiltrated primary melanomas and displayed a predominant peritumoral distribution. These results are new arguments for the development of NK-based therapies in melanoma patients.

12 Article Genital and anorectal mucosal melanoma is associated with cutaneous melanoma in patients and in families. 2013

Cazenave, H / Maubec, E / Mohamdi, H / Grange, F / Bressac-de Paillerets, B / Demenais, F / Avril, M F. ·Service de Dermatologie, APHP, Hôpital Bichat, Paris, France. ·Br J Dermatol · Pubmed #23647170.

ABSTRACT: BACKGROUND: Genital and anorectal mucosal melanomas (GAMMs) are rare compared with cutaneous melanoma (CM). Many epidemiological and genetic studies have been carried out on CM. In contrast, the genetic and environmental risk factors for GAMM have been poorly documented up to now. OBJECTIVES: To compare the distribution of pigmentation and naevus phenotypes, sun exposure and family history of melanoma between patients with GAMM and CM. METHODS: We compared two series of patients, 81 with GAMM and 293 with CM. RESULTS: Patients with GAMM and CM did not show significant differences for phenotypic risk factors. However, patients with GAMM tended to display red hair (11% vs. 5·5%, P = 0·08) and a poor tanning ability (22% vs. 13·3%, P = 0·06) at a higher frequency than patients with CM. A family history of melanoma was significantly more frequent with GAMM than with CM (18% vs. 7·5%, P = 0·005). Apart from the GAMM index case, affected relatives had CM except in one family. The frequency of multiple primary melanomas (MPMs) was similar in the GAMM and CM series (6% vs. 5·3%, P = 0·43). All patients with GAMM and MPM had only one GAMM primary, while the other primary was cutaneous. No CDKN2A germline mutation was detected in patients with GAMM. CONCLUSIONS: This study shows that GAMM and CM may occur in the same patient, and GAMM may develop in a familial setting. The association of both GAMM and CM in patients and families suggests shared genetic factors by these two types of melanoma.

13 Article Familial melanoma: clinical factors associated with germline CDKN2A mutations according to the number of patients affected by melanoma in a family. 2012

Maubec, Eve / Chaudru, Valérie / Mohamdi, Hamida / Blondel, Christophe / Margaritte-Jeannin, Patricia / Forget, Sébastien / Corda, Eve / Boitier, Françoise / Dalle, Stéphane / Vabres, Pierre / Perrot, Jean-Luc / Lyonnet, Dominique Stoppa / Zattara, Hélène / Mansard, Sandrine / Grange, Florent / Leccia, Marie-Thérèse / Vincent-Fetita, Lynda / Martin, Ludovic / Crickx, Béatrice / Joly, Pascal / Thomas, Luc / Anonymous6380732 / Bressac-de Paillerets, Brigitte / Avril, Marie-Françoise / Demenais, Florence. ·INSERM (Institut National de Santé et de Recherche Médicale), Genetic Variation and Human Diseases Unit (U946), Paris, France. eve.maubec@bch.aphp.fr ·J Am Acad Dermatol · Pubmed #22841127.

ABSTRACT: BACKGROUND: Features associated with an increased frequency of cyclin-dependent kinase inhibitor 2A (CDKN2A) mutations have been identified in families with 3 or more patients with cutaneous melanoma (CM). However, in families with 2 patients with CM, which represent the majority of familial melanoma, these factors have been rarely studied. OBJECTIVE: We investigated association of 3 clinical features with the presence of a CDKN2A mutation in a family by extent of CM family clustering (2 vs ≥3 patients with CM among first-degree relatives in a family). METHODS: We included 483 French families that comprised 387 families with 2 patients with CM (F2 families) and 96 families with 3 or more patients with CM (F3+ families). Three clinical factors were examined individually and in a joint analysis: median age at diagnosis younger than 50 years, and 1 or more patient in a family with multiple primary melanoma or with pancreatic cancer. RESULTS: The frequency of CDKN2A mutations was higher in F3+ families (32%) than in F2 families (13%). Although early age at melanoma diagnosis and occurrence of multiple primary melanoma in 1 or more patient were significantly associated with the risk of a CDKN2A mutation in F2 families, early age at melanoma diagnosis and occurrence of pancreatic cancer in a family were significantly associated with CDKN2A mutations in F3+ families. LIMITATIONS: The study was not population based. CONCLUSIONS: This study shows that factors associated with CDKN2A mutations differ by extent of CM family clustering. It indicates that, in France, families with 2 patients with CM are eligible for genetic testing especially when there is an early age at CM diagnosis and/or 1 or more patients with multiple primary melanoma.

14 Article A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma. 2011

Bertolotto, Corine / Lesueur, Fabienne / Giuliano, Sandy / Strub, Thomas / de Lichy, Mahaut / Bille, Karine / Dessen, Philippe / d'Hayer, Benoit / Mohamdi, Hamida / Remenieras, Audrey / Maubec, Eve / de la Fouchardière, Arnaud / Molinié, Vincent / Vabres, Pierre / Dalle, Stéphane / Poulalhon, Nicolas / Martin-Denavit, Tanguy / Thomas, Luc / Andry-Benzaquen, Pascale / Dupin, Nicolas / Boitier, Françoise / Rossi, Annick / Perrot, Jean-Luc / Labeille, Bruno / Robert, Caroline / Escudier, Bernard / Caron, Olivier / Brugières, Laurence / Saule, Simon / Gardie, Betty / Gad, Sophie / Richard, Stéphane / Couturier, Jérôme / Teh, Bin Tean / Ghiorzo, Paola / Pastorino, Lorenza / Puig, Susana / Badenas, Celia / Olsson, Hakan / Ingvar, Christian / Rouleau, Etienne / Lidereau, Rosette / Bahadoran, Philippe / Vielh, Philippe / Corda, Eve / Blanché, Hélène / Zelenika, Diana / Galan, Pilar / Anonymous1370708 / Aubin, François / Bachollet, Bertrand / Becuwe, Céline / Berthet, Pascaline / Bignon, Yves Jean / Bonadona, Valérie / Bonafe, Jean-Louis / Bonnet-Dupeyron, Marie-Noëlle / Cambazard, Fréderic / Chevrant-Breton, Jacqueline / Coupier, Isabelle / Dalac, Sophie / Demange, Liliane / d'Incan, Michel / Dugast, Catherine / Faivre, Laurence / Vincent-Fétita, Lynda / Gauthier-Villars, Marion / Gilbert, Brigitte / Grange, Florent / Grob, Jean-Jacques / Humbert, Philippe / Janin, Nicolas / Joly, Pascal / Kerob, Delphine / Lasset, Christine / Leroux, Dominique / Levang, Julien / Limacher, Jean-Marc / Livideanu, Cristina / Longy, Michel / Lortholary, Alain / Stoppa-Lyonnet, Dominique / Mansard, Sandrine / Mansuy, Ludovic / Marrou, Karine / Matéus, Christine / Maugard, Christine / Meyer, Nicolas / Nogues, Catherine / Souteyrand, Pierre / Venat-Bouvet, Laurence / Zattara, Hélène / Chaudru, Valérie / Lenoir, Gilbert M / Lathrop, Mark / Davidson, Irwin / Avril, Marie-Françoise / Demenais, Florence / Ballotti, Robert / Bressac-de Paillerets, Brigitte. ·1] INSERM, U895 (équipe 1), Equipe labélisée Ligue Contre le Cancer, C3M, 06204 Nice, France [2] Université of Nice Sophia-Antipolis, UFR Médecine, 06204 Nice, France [3] Centre Hospitalier Universitaire de Nice, Service de Dermatologie, 06204 Nice, France [4]. ·Nature · Pubmed #22012259.

ABSTRACT: So far, no common environmental and/or phenotypic factor has been associated with melanoma and renal cell carcinoma (RCC). The known risk factors for melanoma include sun exposure, pigmentation and nevus phenotypes; risk factors associated with RCC include smoking, obesity and hypertension. A recent study of coexisting melanoma and RCC in the same patients supports a genetic predisposition underlying the association between these two cancers. The microphthalmia-associated transcription factor (MITF) has been proposed to act as a melanoma oncogene; it also stimulates the transcription of hypoxia inducible factor (HIF1A), the pathway of which is targeted by kidney cancer susceptibility genes. We therefore proposed that MITF might have a role in conferring a genetic predisposition to co-occurring melanoma and RCC. Here we identify a germline missense substitution in MITF (Mi-E318K) that occurred at a significantly higher frequency in genetically enriched patients affected with melanoma, RCC or both cancers, when compared with controls. Overall, Mi-E318K carriers had a higher than fivefold increased risk of developing melanoma, RCC or both cancers. Codon 318 is located in a small-ubiquitin-like modifier (SUMO) consensus site (ΨKXE) and Mi-E318K severely impaired SUMOylation of MITF. Mi-E318K enhanced MITF protein binding to the HIF1A promoter and increased its transcriptional activity compared to wild-type MITF. Further, we observed a global increase in Mi-E318K-occupied loci. In an RCC cell line, gene expression profiling identified a Mi-E318K signature related to cell growth, proliferation and inflammation. Lastly, the mutant protein enhanced melanocytic and renal cell clonogenicity, migration and invasion, consistent with a gain-of-function role in tumorigenesis. Our data provide insights into the link between SUMOylation, transcription and cancer.

15 Article Pregnancy promotes melanoma metastasis through enhanced lymphangiogenesis. 2011

Khosrotehrani, Kiarash / Nguyen Huu, Sau / Prignon, Aurélie / Avril, Marie-Françoise / Boitier, Françoise / Oster, Michèle / Mortier, Laurent / Richard, Marie-Aleth / Maubec, Eve / Kerob, Delphine / Mansard, Sandrine / Merheb, Charbel / Moguelet, Philippe / Nassar, Dany / Guégan, Sarah / Aractingi, Selim. ·Université Pierre et Marie Curie, University Paris 06, Paris, France. ·Am J Pathol · Pubmed #21435464.

ABSTRACT: The relationships of pregnancy and melanoma have been debatable. Our aim was to assess the influence of gestation on the course of melanoma in a classic murine model of tumor progression and in women. B16 mouse melanoma cells were injected in nonpregnant or pregnant mice on day 5 of gestation. Animals were evaluated for tumor progression, metastases, and survival. Tumor sections were analyzed for lymphatic and blood vessel number and relative surface and expression of angiogenic growth factors. Finally, primary melanomas from pregnant and nonpregnant women, matched for age and tumor thickness, were also considered. Tumor growth, metastasis, and mortality were increased in B16-injected pregnant mice. Tumors displayed an increase in intratumoral lymphangiogenesis during gestation. This increased lymphatic angiogenesis was not observed in normal skin during gestation, showing its specificity to the tumor. An analysis of melanoma from pregnant and matched nonpregnant women showed a similar increase in lymphatic vessels. Tumors from pregnant mice had increased expression of vascular endothelial growth factor A at the RNA and protein levels. The increased vascular endothelial growth factor A production by melanoma cells could be reproduced in culture using pregnant mouse serum. In conclusion, pregnancy results in increased lymphangiogenesis and subsequent metastasis. Caution should be applied in the management of patients with advanced-stage melanoma during gestation.

16 Article Progressive upregulation of PD-1 in primary and metastatic melanomas associated with blunted TCR signaling in infiltrating T lymphocytes. 2011

Chapon, Maxime / Randriamampita, Clotilde / Maubec, Eve / Badoual, Cécile / Fouquet, Stéphane / Wang, Shu-Fang / Marinho, Eduardo / Farhi, David / Garcette, Marylène / Jacobelli, Simon / Rouquette, Alexandre / Carlotti, Agnès / Girod, Angélique / Prévost-Blondel, Armelle / Trautmann, Alain / Avril, Marie-Françoise / Bercovici, Nadège. ·Institut Cochin, Inserm, U1016, Paris, France. ·J Invest Dermatol · Pubmed #21346771.

ABSTRACT: Programmed death-1 (PD-1) is involved in T-cell tolerance to self-antigens. For some cancers, it has been suggested that the expression of a ligand of PD-1, namely PD-L1, could contribute to tumor escape from immune destruction. Nevertheless, the relationship between PD-1 expression on tumor-infiltrating T lymphocytes (TILs), disease stage, and TIL responsiveness is still poorly documented. In this study, we show that freshly isolated CD4(+) and CD8(+) TILs express substantial levels of PD-1 in primary melanomas. The expression of PD-1 was further increased at later stages in distant cutaneous metastases, especially on CD8(+) TILs. The expression of PD-1 ligands was frequent only in metastases, on both tumor cells and tumor-derived myeloid cells. TILs isolated from these cutaneous tumors are poorly reactive ex vivo, with blunted calcium response and IFN-γ production after TCR stimulation. Surprisingly, in distinct parts of a primary melanoma, either invasive or regressing, we show that TILs similarly express PD-1 and remain dysfunctional. The expressions of PD-1 and PD-L1 in metastatic melanoma lesions could be considered as witnesses of an unsuccessful anti-tumoral immune response, but the direct involvement of PD-1 in the severity of the disease, and the importance of TILs in tumor regression, remain to be established.

17 Article Sentinel lymph node biopsy or nodal observation in melanoma: a prospective study of patient choices. 2011

Grange, Florent / Maubec, Eve / Barbe, Coralie / Kassouma, Jamal / Vitry, Fabien / Johanet, Hubert / Granel-Brocard, Florence / Boitier, Francoise / Girod, Angelique / Couturaud, Benoit / Saez, Pierre / Albert, Sebastien / Le Clainche, Annick / Descamps, Vincent / Avril, Marie Francoise. ·Service de Dermatologie, Hôpital Robert Debré, Reims, France. fgrange@chu-reims.fr ·Dermatol Surg · Pubmed #21269352.

ABSTRACT: BACKGROUND: There is no consensus regarding the therapeutic utility of sentinel lymph node biopsy (SLNB) versus that of nodal observation (NO) in melanoma. OBJECTIVE: To prospectively evaluate a standardized counseling procedure and its effect on patient choices to undergo SLNB or NO. METHODS: In four centers, patients with melanoma eligible for SLNB or NO received a complete counseling procedure that included verbal information from dermatologists and surgeons, a detailed information sheet, and a written consent form. Data collected included patient and tumor characteristics, counseling conditions, and specialties of informing doctors. Factors influencing patients' choices were studied using multivariate analysis. RESULTS: Of 343 consecutive patients, 309 were offered SLNB and NO and received complete verbal and written information from a dermatologist alone (62%) or in association with a surgeon (38%). Approximately half took advice from trusted persons, and half asked for additional time before making a decision; 268 (86.7%) ultimately decided to undergo SLNB. Multivariate analysis showed that older patients, those with a head and neck melanoma, and those informed without a surgeon present were more likely to prefer NO. CONCLUSIONS: This counseling procedure was easily implemented in clinical practice. Patients favored SLNB but were able to understand uncertainties and express preferences.

18 Article Characteristics of the coexistence of melanoma and renal cell carcinoma. 2010

Maubec, Eve / Chaudru, Valérie / Mohamdi, Hamida / Grange, Florent / Patard, Jean-Jacques / Dalle, Stéphane / Crickx, Béatrice / Paillerets, Brigitte Bressac-de / Demenais, Florence / Avril, Marie-Françoise. ·National Institute of Health and Medical Research, Paris, France. eve.maubec@bch.aphp.fr ·Cancer · Pubmed #21218461.

ABSTRACT: BACKGROUND: Patients with melanoma (MM) have an increased risk of kidney cancer, and there is an excess risk of MM among patients with renal cell carcinoma (RCC). The objective of the current study was to analyze a series of 42 patients with both MM and RCC to identify clinical and pathologic features as well as risk factors of this association. METHODS: Clinical and pathologic characteristics of 42 patients who developed both MM and RCC (the MM + RCC series) were compared with 2 published series in each cancer alone: a series of 293 patients with MM (MM series) and a series of 1527 patients with RCC (RCC series). RESULTS: RCC was diagnosed concomitantly or after MM in 83% of patients in the MM + RCC series. Those patients displayed a high proportion of asymptomatic RCC at diagnosis (70%) and a higher frequency of stage I tumors (61%) than patients in the RCC series. Compared with the MM series, patients in the MM + RCC series more often were men, had a higher frequency of blond/red hair, had poor tanning ability, and had a higher number of nevi. In addition, patients in the MM + RCC series had a high aggregation of other malignancies (mainly skin cancers) and a significantly higher frequency of family history of MM (P = .005). Only 2 cyclin-dependent kinase 2A gene (CDKN2A) germline mutations were identified among patients in the MM + RCC series who also were members of MM-prone families. CONCLUSIONS: The high aggregation of cancers among patients in the MM + RCC series and the familial clustering of MM argued for a genetic predisposition that may be partly independent of CDKN2A.

19 Article [Melanoma in HIV patients: 14 cases]. 2010

Qasmi, S / Sutra-Loubet, C / Maubec, E / Boitier, F / Duvillard, P / Carlotti, A / Marinho, E / Jacobelli, S / Franck, N / Gorin, I / Vacher-Lavenu, M C / Bouscarat, F / Crickx, B / Dupin, N / Avril, M F. ·Service de Dermatologie, Université Paris 5, Hôpital Cochin-pavillon Tornier, 89, rue d'Assas, AP-HP, 75006 Paris, France. ·Ann Dermatol Venereol · Pubmed #21134578.

ABSTRACT: BACKGROUND: a clinical study of 14 patients presenting both malignant melanoma and HIV infection, and analysis of the literature to determine the frequency and specific features of this association. PATIENTS AND METHODS: ten men and four women of median age 43 years were included. In 50% of cases, the primary melanoma consisted of spreading superficial melanoma with a mean Breslow thickness of 2.83 mm. In two cases, regional lymph node metastasis was discovered but with no primary melanoma being identified. HIV infection was already documented on diagnosis of melanoma in 11 cases, and it was discovered in three cases at the time of surgery for melanoma (treatment of the primary melanoma in two cases, and in one case, regional lymph node dissection two years after the initial diagnosis). Eight patients died within a mean period of 39 months, with melanoma being the cause of death in six cases. Following relapse of melanoma, the course of the disease was severe, with mean stage IV survival of 3.6 months. No response to chemotherapy was observed where such treatment was feasible. DISCUSSION: the presence of HIV appears to be an aggravating factor for the outcome of metastatic melanoma. CONCLUSION: our study suggests the importance of clinical examination of pigmented lesions in HIV patients in order to ensure early identification of melanoma.

20 Article [Tumour regression is not predictive for higher risk of sentinel node involvement in thin melanomas (Breslow thickness < or = 1 mm)]. 2010

Kramkimel, N / Maubec, E / Boitier, F / Cavalcanti, A / Beldi, M / Mamelle, G / Kolb, F / Duvillard, P / Avril, M-F. ·Service de dermatologie, hôpital Cochin, AP-HP, université Paris-5, pavillon Tarnier, 89, rue d'Assas, 75006 Paris, France. ·Ann Dermatol Venereol · Pubmed #20417360.

ABSTRACT: BACKGROUND: Thin melanomas (Breslow thickness < or = 1 mm) are considered highly curable. The aim of this study was to evaluate the correlation between histological tumour regression and sentinel lymph node (SLN) involvement in thin melanomas. PATIENTS AND METHODS: This was a retrospective single-centre study of 34 patients with thin melanomas undergoing SLN biopsy between April 1998 and January 2005. RESULTS: The study included 14 women and 20 men of mean age 56.3 years. Melanomas were located on the neck (n=3), soles (n=4), trunk (n=13) and extremities (n=14). Pathological examination showed 25 SSM, four acral lentiginous melanomas, three in situ melanomas, one nodular melanoma and one unclassified melanoma with a mean Breslow thickness of 0.57 mm. Histological tumour regression was observed in 26 over 34 cases and ulceration was found in one case. Clark levels were as follows: I (n=3), II (n=20), III (n=9), IV (n=2). Growth phase was available in 15 cases (seven radial and eight vertical). Mitotic rates, available in 24 cases, were: 0 (n=9), 1 (n=11), 2 (n=2), 3 (n=1), 6 (n=1). One patient with histological tumour regression (2.9% of cases and 3.8% of cases with regressing tumours) had a metastatic SLN. One patient negative for SLN had a lung relapse and died of the disease. Mean follow-up was 26.2 months. CONCLUSION: The results of the present study and the analysis of the literature show that histological regression of the primary tumour does not seem predictive of higher risk of SLN involvement in thin melanomas. This suggests that screening for SLN is not indicated in thin melanomas, even those with histological regression.

21 Article Management and outcome of metastatic melanoma during pregnancy. 2010

Pagès, C / Robert, C / Thomas, L / Maubec, E / Sassolas, B / Granel-Brocard, F / Chevreau, C / De Raucourt, S / Leccia, M-T / Fichet, D / Khammari, A / Boitier, F / Stoebner, P-E / Dalac, S / Celerier, P / Aubin, F / Viguier, M. ·Service de Dermatologie, Université Paris VII, Hôpital Saint-Louis, INSERM U697, 1 Avenue Claude-Vellefaux, 75475 Paris Cedex 10, France. ·Br J Dermatol · Pubmed #19804595.

ABSTRACT: BACKGROUND: Although metastatic melanoma occurrence during pregnancy challenges the physician in several ways, only a few studies have been published. OBJECTIVES: Our aim was to investigate therapeutic management together with maternal and fetal outcomes in pregnant women with advanced melanoma. METHODS: A French national retrospective study was conducted in 34 departments of Dermatology or Oncology. All patients with American Joint Committee on Cancer (AJCC) stage III/IV melanoma diagnosed during pregnancy were included. Data regarding melanoma history, pregnancy, treatment, delivery, maternal and infant outcomes were collected. RESULTS: Twenty-two women were included: 10 AJCC stage III and 12 stage IV. Abortion was performed in three patients. Therapeutic abstention during pregnancy was observed in three cases, 14 patients underwent surgery, four patients received chemotherapy and one patient was treated with brain radiotherapy alone. The median gestational age was 36 weeks amenorrhoea. Neither neonatal metastases nor deformities were observed. Placenta metastases were found in one case. Among 18 newborns, 17 are currently alive (median follow up, 17 months); one died of sudden infant death. The 2-year maternal survival rates were 56% (stage III) and 17% (stage IV). CONCLUSIONS: Faced with metastatic melanoma, a majority of women chose to continue with pregnancy, giving birth, based on our samples, to healthy, frequently premature infants. Except during the first trimester of pregnancy, conventional melanoma treatment was applied. No serious side effect was reported, except one case of miscarriage after surgery. Mortality rates do not suggest a worsened prognosis due to pregnancy but larger prospective controlled studies are necessary to assess this specific point.

22 Article Fetal microchimeric cells participate in tumour angiogenesis in melanomas occurring during pregnancy. 2009

Nguyen Huu, Sau / Oster, Michèle / Avril, Marie-Françoise / Boitier, Françoise / Mortier, Laurent / Richard, Marie-Aleth / Kerob, Delphine / Maubec, Eve / Souteyrand, Pierre / Moguelet, Philippe / Khosrotehrani, Kiarash / Aractingi, Selim. ·Laboratoire de Physiopathologie du Développement, Universite Pierre et Marie Currie University of Paris 06, EA4053, Paris, France. ·Am J Pathol · Pubmed #19147820.

ABSTRACT: Melanoma is a major malignancy in younger individuals that accounts for 8% of all neoplasias associated with gestation. During pregnancy, a small number of fetal cells enter the maternal circulation. These cells persist and then migrate to various maternal tissues where they may engraft and differentiate, particularly if there is organ damage, adopting the phenotype of the host organ. To understand the relationship between melanoma and pregnancy, we analyzed these tumors in both humans and mice. Fetal cells were detected in 63% of human primary melanomas versus 12% in nevi during pregnancy (P = 0.034) and in 57% of B16 melanomas in pregnant mice but never in normal skin (P = 0.000022). More than 50% of these fetal cells expressed the CD34, CD31, or von Willebrand factor endothelial cell markers. In addition, the Lyve-1 lymphatic antigen was expressed by more than 30% of fetal cells in mice. In conclusion, we show that melanomas during pregnancy frequently harbor fetal cells that have an endothelial phenotype. Further studies are needed to assess whether the fetal contribution to lymphangiogenesis may alter the prognosis of the maternal tumor.

23 Article The contribution of large genomic deletions at the CDKN2A locus to the burden of familial melanoma. 2008

Lesueur, F / de Lichy, M / Barrois, M / Durand, G / Bombled, J / Avril, M-F / Chompret, A / Boitier, F / Lenoir, G M / Anonymous2230603 / Bressac-de Paillerets, B / Baccard, Monique / Bachollet, Bertrand / Berthet, Pascaline / Bonadona, Valérie / Bonnetblanc, Jean-Marie / Caron, Olivier / Chevrant-Breton, Jacqueline / Cuny, Jean-François / Dalle, Stéphane / Delaunay, Michèle / Demange, Liliane / De Quatrebarbes, Julie / Doré, Jean-François / Frénay, Marc / Fricker, Jean-Pierre / Gauthier-Villars, Marion / Gesta, Paul / Giraud, Sophie / Gorry, Philippe / Grange, Florent / Green, Andrew / Huiart, Laetitia / Janin, Nicolas / Joly, Pascal / Kérob, Delphine / Lasset, Christine / Leroux, Dominique / Limacher, Jean-Marc / Longy, Michel / Mansard, Sandrine / Marrou, Karine / Martin-Denavit, Tanguy / Mateus, Christine / Maubec, Eve / Olivier-Faivre, Laurence / Orlandini, Vincent / Pujol, Pascal / Sassolas, Bruno / Stoppa-Lyonnet, Dominique / Thomas, Luc / Vabres, Pierre / Venat, Laurence / Wierzbicka, Ewa / Zattara, Hélène. ·Groupe Mélanome, Institut Gustave Roussy, FRE2939 CNRS-Université Paris-Sud, Villejuif, France. ·Br J Cancer · Pubmed #18612309.

ABSTRACT: Mutations in two genes encoding cell cycle regulatory proteins have been shown to cause familial cutaneous malignant melanoma (CMM). About 20% of melanoma-prone families bear a point mutation in the CDKN2A locus at 9p21, which encodes two unrelated proteins, p16(INK4a) and p14(ARF). Rare mutations in CDK4 have also been linked to the disease. Although the CDKN2A gene has been shown to be the major melanoma predisposing gene, there remains a significant proportion of melanoma kindreds linked to 9p21 in which germline mutations of CDKN2A have not been identified through direct exon sequencing. The purpose of this study was to assess the contribution of large rearrangements in CDKN2A to the disease in melanoma-prone families using multiplex ligation-dependent probe amplification. We examined 214 patients from independent pedigrees with at least two CMM cases. All had been tested for CDKN2A and CDK4 point mutation, and 47 were found positive. Among the remaining 167 negative patients, one carried a novel genomic deletion of CDKN2A exon 2. Overall, genomic deletions represented 2.1% of total mutations in this series (1 of 48), confirming that they explain a very small proportion of CMM susceptibility. In addition, we excluded a new gene on 9p21, KLHL9, as being a major CMM gene.

24 Article [Melanoma in invisible naevus spilus]. 2008

Livory, M / Descamps, V / Pelletier, F / Maubec, E / Faivre, B / Marinho, E / Humbert, P / Crickx, B / Aubin, F. ·Service de dermatologie, hôpital Bichat, université Denis-Diderot Paris-7, Assistance publique-Hôpitaux de Paris, 46, rue Henri-Huchard, 75018 Paris, France. ·Ann Dermatol Venereol · Pubmed #18342074.

ABSTRACT: BACKGROUND: Diagnosis of naevus lesions may be complex where they contain little or no pigmentation. Naevus spilus (or naevus on naevus) is, generally, readily identified by the difference in pigmentation between overlying and underlying naevi and healthy skin. Malignant transformation of naevus spilus is rare. We report two cases of melanoma in which surgical procedures revealed underlying melanocyte lesions, diagnosed at histology but undetectable on clinical examination. PATIENTS AND METHODS: Two patients were operated for melanoma in which surgery, at a site remote from the melanoma, suggested incomplete relapse despite the fact that previous clinical examination had indicated healthy skin. A diagnosis was made of melanoma in invisible naevus spilus. DISCUSSION: Diagnosis of melanoma in invisible naevus spilus may be suspected where several naevi are found together in a specific area. The main problem is the therapeutic stance to be adopted since complete excision of the underlying naevi is difficult in practice. Wood's light examination may be helpful.