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Mesothelioma: HELP
Articles by Luka Brčić
Based on 10 articles published since 2008
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Between 2008 and 2019, L. Brcic wrote the following 10 articles about Mesothelioma.
 
+ Citations + Abstracts
1 Article Expression of plakophilin 3 in diffuse malignant pleural mesothelioma. 2018

Mašić, Silvija / Brčić, Luka / Krušlin, Božo / Šepac, Ana / Pigac, Biserka / Stančić-Rokotov, Dinko / Jakopović, Marko / Seiwerth, Sven. ·Clinical Deparment of Pathology and Cytology, "Ljudevit Jurak", Sestre Milosrdnice University Hospital Centre, Zagreb, Croatia. silvijamasic57@gmail.com. · Institute of Pathology, University of Zagreb, Zagreb, Croatia. · Institute of Pathology, Medical University of Graz, Graz, Austria. · Clinical Deparment of Pathology and Cytology, "Ljudevit Jurak", Sestre Milosrdnice University Hospital Centre, Zagreb, Croatia. · Department of Pathology, Cytology and Forensic Medicine, Varaždin General Hospital, Varaždin, Croatia. · Department of Thoracic Surgery, University of Zagreb, Zagreb, Croatia. · Clinical Department of Pulmology, Clinical Hospital Centre Zagreb, Zagreb, Croatia. · Clinical Department of Pathology and Cytology, Clinical Hospital Centre Zagreb, Zagreb, Croatia. ·Histol Histopathol · Pubmed #29722422.

ABSTRACT: Diffuse malignant pleural mesothelioma (DMPM) is the most common primary malignant pleural neoplasm still posing major diagnostic, prognostic and therapeutic challenges. Plakophilins are structural proteins considered to be important for cell stability and adhesion in both tumor and normal tissues. Plakophilin 3 is a protein present in desmosomes of stratified and simple epithelia of normal tissues with presence in malignant cells of various tumors where it participates in the process of tumorigenesis. The aim of this study was to investigate the expression of plakophilin 3 protein in DMPM, but also to study its prognostic significance and relation to histologically accessible parameters of aggressive growth. Archival samples of tissue with established diagnosis of DMPM and samples of normal pleural tissue were used. Tumor samples were classified into three histological types of DMPM (epithelioid, sarcomatoid and biphasic). Additional subclassification of epithelioid mesotheliomas into nine patterns based on the prevalent histological component of the tumor was then performed. After immunohistochemical staining, cytoplasmic and membrane immunopositivity of tumor cells was assesed by scoring the intensity of the staining from 0 (no staining) to 4 (very strong staining). Prognostic value and expression of plakophilin 3 with consideration to histologically estimated aggression in tumor growth were then statistically analyzed using non- parametric tests. The results demonstrated higher level of plakophilin 3 expression in tumor samples with histologically more aggressive tumor growth, but no significant prognostic value. According to our study, plakophilin 3 appears to be involved in tumor invasion in malignant mesothelioma.

2 Article FGF2 and EGF induce epithelial-mesenchymal transition in malignant pleural mesothelioma cells via a MAPKinase/MMP1 signal. 2018

Schelch, Karin / Wagner, Christina / Hager, Sonja / Pirker, Christine / Siess, Katharina / Lang, Elisabeth / Lin, Ruby / Kirschner, Michaela B / Mohr, Thomas / Brcic, Luka / Marian, Brigitte / Holzmann, Klaus / Grasl-Kraupp, Bettina / Krupitza, Georg / Laszlo, Viktoria / Klikovits, Thomas / Dome, Balazs / Hegedus, Balazs / Garay, Tamas / Reid, Glen / van Zandwijk, Nico / Klepetko, Walter / Berger, Walter / Grusch, Michael / Hoda, Mir Alireza. ·Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria. · Asbestos Diseases Research Institute (ADRI), Sydney, NSW, Australia. · School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia. · Institute of Pathology, Medical University of Graz, Graz, Austria. · Department of Clinical Pathology, Medical University of Vienna, Vienna, Austria. · Translational Thoracic Oncology Laboratory, Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna. · Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria. · Department of Tumor Biology, National Koranyi Institute of Pulmonology, Budapest, Hungary. · Department of Thoracic Surgery, National Institute of Oncology and Semmelweis University, Budapest, Hungary. · MTA-SE Molecular Oncology Research Group, Hungarian Academy of Sciences, Budapest, Hungary. · Department of Thoracic Surgery, Ruhrlandklinik, University Clinic Essen, University of Duisburg-Essen, Essen, Germany. · School of Medicine, University of Sydney, NSW, Australia. ·Carcinogenesis · Pubmed #29635378.

ABSTRACT: Malignant pleural mesothelioma (MPM), an aggressive malignancy affecting pleural surfaces, occurs in three main histological subtypes. The epithelioid and sarcomatoid subtypes are characterized by cuboid and fibroblastoid cells, respectively. The biphasic subtype contains a mixture of both. The sarcomatoid subtype expresses markers of epithelial-mesenchymal transition (EMT) and confers the worst prognosis, but the signals and pathways controlling EMT in MPM are not well understood. We demonstrate that treatment with FGF2 or EGF induced a fibroblastoid morphology in several cell lines from biphasic MPM, accompanied by scattering, decreased cell adhesion and increased invasiveness. This depended on the MAP-kinase pathway but was independent of TGFβ or PI3-kinase signaling. In addition to changes in known EMT markers, microarray analysis demonstrated differential expression of MMP1, ESM1, ETV4, PDL1 and BDKR2B in response to both growth factors and in epithelioid versus sarcomatoid MPM. Inhibition of MMP1 prevented FGF2-induced scattering and invasiveness. Moreover, in MPM cells with sarcomatoid morphology, inhibition of FGF/MAP-kinase signaling induced a more epithelioid morphology and gene expression pattern. Our findings suggest a critical role of the MAP-kinase axis in the morphological and behavioral plasticity of mesothelioma.

3 Article Reproducibility of Malignant Pleural Mesothelioma Histopathologic Subtyping. 2018

Brcic, Luka / Vlacic, Gregor / Quehenberger, Franz / Kern, Izidor. ·From the Institute of Pathology (Dr Brcic) and the Institute for Medical Informatics, Statistics and Documentation (Dr Quehenberger), Medical University of Graz, Graz, Austria · and Cytology and Pathology Laboratory, University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia (Drs Vlacic and Kern). ·Arch Pathol Lab Med · Pubmed #29509030.

ABSTRACT: CONTEXT: - Malignant pleural mesothelioma (MPM) is a rare tumor with poor prognosis. Several studies have analyzed potential prognostic markers, but histologic type remains the single most important prognostic factor. Histologic subtypes of epithelioid MPM seem to have prognostic and therapeutic implications. Interobserver agreement in histologic pattern classification should be high. OBJECTIVE: - To assess interobserver and intraobserver reproducibility in histologic differentiation between the main types of MPMs, and in further subtyping of epithelioid-type mesothelioma. DESIGN: - One representative hematoxylin-eosin-stained slide was selected from the archive for each of 200 patients with MPM. They were reviewed independently by 3 pathologists and classified according to the current World Health Organization classification of pleural tumors. After the first round of evaluations, a consensus meeting was organized where problems were addressed and representative images for each histologic category were selected. Two months later, cases were reevaluated by all 3 pathologists. RESULTS: - After the first round, overall interobserver agreement for histologic subtyping of mesothelioma was fair (κ, 0.36). The agreement was increased to substantial (κ, 0.63) in the second round. Improvement was found in interobserver agreement for all types of MPM and for most epithelioid subtypes. CONCLUSIONS: - Moderate to substantial agreement in histologic typing and subtyping of MPM can be achieved. However, training with additional clarification of diagnostic criteria, their strict application, and help from consensus-based illustrative images is needed.

4 Article Nuclear grade and necrosis predict prognosis in malignant epithelioid pleural mesothelioma: a multi-institutional study. 2018

Rosen, Lauren E / Karrison, Theodore / Ananthanarayanan, Vijayalakshmi / Gallan, Alexander J / Adusumilli, Prasad S / Alchami, Fouad S / Attanoos, Richard / Brcic, Luka / Butnor, Kelly J / Galateau-Sallé, Françoise / Hiroshima, Kenzo / Kadota, Kyuichi / Klampatsa, Astero / Stang, Nolween Le / Lindenmann, Joerg / Litzky, Leslie A / Marchevsky, Alberto / Medeiros, Filomena / Montero, M Angeles / Moore, David A / Nabeshima, Kazuki / Pavlisko, Elizabeth N / Roggli, Victor L / Sauter, Jennifer L / Sharma, Anupama / Sheaff, Michael / Travis, William D / Vigneswaran, Wickii T / Vrugt, Bart / Walts, Ann E / Tjota, Melissa Y / Krausz, Thomas / Husain, Aliya N. ·Department of Pathology, The University of Chicago Medicine, Chicago, IL, USA. · Department of Public Health Sciences, The University of Chicago, Chicago, IL, USA. · Department of Pathology, Loyola University Medical Center, Chicago, IL, USA. · Department of Thoracic Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Cellular Pathology, University Hospital of Wales, Cardiff, UK. · Department of Cellular Pathology, University Hospital of Wales and Cardiff University, Cardiff, UK. · Medical University of Graz, Institute of Pathology, Graz, Austria. · Department of Pathology, University of Vermont Medical Center, Burlington, VT, USA. · Centre Léon Bérard, BioPathologie, Lyon, France. · Department of Pathology, Tokyo Women's Medical University Yachiyo Medical Center, Yachiyo, Japan. · Department of Diagnostic Pathology, Kagawa University, Takamatsu, Japan. · Division of Pulmonary, Allergy and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. · Division of Thoracic and Hyperbaric Surgery, Department of Surgery,Medical University of Graz, Graz, Austria. · ,Department of Pathology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. · Department of Pathology & Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA. · Basildon & Thurrock University Hospital, Department of Pathology, Basildon, UK. · Department of Histopathology, Royal Brompton and Harefield Hospitals Imperial College of London, London, UK. · Department of Cancer Studies, University of Leicester, Leicester, UK. · Fukuoka University, Department of Pathology, Fukuoka, Japan. · Department of Pathology, Duke University Medical Center, Durham, NC, USA. · Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Pathology, University of Pittsburgh Medical Center and VA Pittsburgh Healthcare System, Pittsburgh, PA, USA. · Department of Pathology, Barts Health NHS Trust, London, UK. · Department of Thoracic and Cardiovascular Surgery, Loyola University Medical Center, Chicago, IL, USA. · University Hospital Zurich, Institute for Pathology and Molecular Pathology, Zurich, Switzerland. ·Mod Pathol · Pubmed #29327706.

ABSTRACT: A recently described nuclear grading system predicted survival in patients with epithelioid malignant pleural mesothelioma. The current study was undertaken to validate the grading system and to identify additional prognostic factors. We analyzed cases of epithelioid malignant pleural mesothelioma from 17 institutions across the globe from 1998 to 2014. Nuclear grade was computed combining nuclear atypia and mitotic count into a grade of I-III using the published system. Nuclear grade was assessed by one pathologist for three institutions, the remaining were scored independently. The presence or absence of necrosis and predominant growth pattern were also evaluated. Two additional scoring systems were evaluated, one combining nuclear grade and necrosis and the other mitotic count and necrosis. Median overall survival was the primary endpoint. A total of 776 cases were identified including 301 (39%) nuclear grade I tumors, 354 (45%) grade II tumors and 121 (16%) grade III tumors. The overall survival was 16 months, and correlated independently with age (P=0.006), sex (0.015), necrosis (0.030), mitotic count (0.001), nuclear atypia (0.009), nuclear grade (<0.0001), and mitosis and necrosis score (<0.0001). The addition of necrosis to nuclear grade further stratified overall survival, allowing classification of epithelioid malignant pleural mesothelioma into four distinct prognostic groups: nuclear grade I tumors without necrosis (29 months), nuclear grade I tumors with necrosis and grade II tumors without necrosis (16 months), nuclear grade II tumors with necrosis (10 months) and nuclear grade III tumors (8 months). The mitosis-necrosis score stratified patients by survival, but not as well as the combination of necrosis and nuclear grade. This study confirms that nuclear grade predicts survival in epithelioid malignant pleural mesothelioma, identifies necrosis as factor that further stratifies overall survival, and validates the grading system across multiple institutions and among both biopsy and resection specimens. An alternative scoring system, the mitosis-necrosis score is also proposed.

5 Article Circulating activin A is a novel prognostic biomarker in malignant pleural mesothelioma - A multi-institutional study. 2016

Hoda, Mir Alireza / Dong, Yawen / Rozsas, Anita / Klikovits, Thomas / Laszlo, Viktoria / Ghanim, Bahil / Stockhammer, Paul / Ozsvar, Judit / Jakopovic, Marko / Samarzija, Miroslav / Brcic, Luka / Bendek, Matyas / Szirtes, Ildiko / Reid, Glen / Kirschner, Michaela B / Kao, Steven C / Opitz, Isabelle / Weder, Walter / Frauenfelder, Thomas / Nguyen-Kim, Thi Dan Linh / Aigner, Clemens / Klepetko, Walter / van Zandwijk, Nico / Berger, Walter / Dome, Balazs / Grusch, Michael / Hegedus, Balazs. ·Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria; Institute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University of Vienna, Vienna, Austria. · Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria. · Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria; National Koranyi Institute of Pulmonology, Budapest, Hungary. · University of Zagreb, School of Medicine, Department for Respiratory Diseases Jordanovac, University Hospital Center Zagreb, Croatia. · Medical University of Graz, Institute of Pathology, Graz, Austria. · National Koranyi Institute of Pulmonology, Budapest, Hungary. · 2nd Institute of Pathology Semmelweis University, Budapest, Hungary. · Asbestos Diseases Research Institute, Sydney, Australia. · University Hospital Zurich, Division of Thoracic Surgery, Zurich, Switzerland. · University Hospital Zurich, Department of Diagnostic and Interventional Radiology, Zurich, Switzerland. · Department of Thoracic Surgery, Ruhrlandklinik, Essen, Germany. · Institute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University of Vienna, Vienna, Austria. · Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria; National Koranyi Institute of Pulmonology, Budapest, Hungary; Department of Thoracic Surgery, National Institute of Oncology and Semmelweis University, Budapest, Hungary; Department of Biomedical Imaging and Image-guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna, Vienna, Austria. · Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria; Department of Biomedical Imaging and Image-guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna, Vienna, Austria; MTA-SE Molecular Oncology Research Group, Hungarian Academy of Sciences, Budapest, Hungary. Electronic address: balazs.hegedus@meduniwien.ac.at. ·Eur J Cancer · Pubmed #27288871.

ABSTRACT: INTRODUCTION: The deregulation of activin expression is often observed in various malignancies. Previous studies indicate that activin A plays a protumourigenic role in malignant pleural mesothelioma (MPM). The aim of the study was to evaluate circulating activin A level as a biomarker in MPM. METHODS: Plasma samples were collected from 129 MPM patients in four institutions at the time of diagnosis or before surgical resection. Samples from 45 healthy individuals and from 16 patients with non-malignant pleural diseases served as controls. Circulating activin A was measured by enzyme-linked immunosorbent assay and correlated to clinicopathological variables. RESULTS: Plasma activin A level was significantly elevated in MPM patients (862 ± 83 pg/ml) when compared to healthy controls (391 ± 21 pg/ml; P < 0.0001). Patients with pleuritis or fibrosis only showed a modest increase (versus controls; 625 ± 95 pg/ml; P = 0.0067). Sarcomatoid (n = 10, 1629 ± 202 pg/ml, P = 0.0019) and biphasic (n = 23, 1164 ± 233 pg/ml, P = 0.0188) morphology were associated with high activin A levels when compared to epithelioid histology (n = 94, 712 ± 75 pg/ml). The tumour volume showed a positive correlation with increased circulating activin A levels. MPM patients with below median activin A levels had a significantly longer overall survival when compared to those with high activin A levels (median survival 735 versus 365 d, P < 0.0001). Importantly, circulating activin A levels were exclusively prognostic in epithelioid MPM. CONCLUSIONS: Our findings suggest that the measurement of circulating activin A may support the histological classification of MPM and at the same time help to identify epithelioid MPM patients with poor prognosis.

6 Article Epigenetic down-regulation of integrin α7 increases migratory potential and confers poor prognosis in malignant pleural mesothelioma. 2015

Laszlo, Viktoria / Hoda, Mir Alireza / Garay, Tamas / Pirker, Christine / Ghanim, Bahil / Klikovits, Thomas / Dong, Yawen W / Rozsas, Anita / Kenessey, Istvan / Szirtes, Ildiko / Grusch, Michael / Jakopovic, Marko / Samarzija, Miroslav / Brcic, Luka / Kern, Izidor / Rozman, Ales / Popper, Helmut / Zöchbauer-Müller, Sabine / Heller, Gerwin / Altenberger, Corinna / Ziegler, Barbara / Klepetko, Walter / Berger, Walter / Dome, Balazs / Hegedus, Balazs. ·Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Austria. · Department of Biological Physics, Eötvös University, Budapest, Hungary. · 2nd Department of Pathology, Semmelweis University, Budapest, Hungary. · Institute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University of Vienna, Austria. · National Koranyi Institute of Pulmonology, Budapest, Hungary. · University of Zagreb, School of Medicine, Department for Respiratory Diseases Jordanovac, University Hospital Center Zagreb, Croatia. · University of Zagreb, School of Medicine, Institute of Pathology, Croatia. · Institute of Pathology, Medical University of Graz, Austria. · University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia. · Division of Oncology, Department of Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria. · Department of Thoracic Surgery, National Institute of Oncology and Semmelweis University, Budapest, Hungary. · Department of Biomedical Imaging and Image-guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna, Vienna, Austria. · MTA-SE Molecular Oncology Research Group, Hungarian Academy of Sciences, Budapest, Hungary. ·J Pathol · Pubmed #26011651.

ABSTRACT: Malignant pleural mesothelioma (MPM) is a devastating malignancy characterized by invasive growth and rapid recurrence. The identification and inhibition of molecular components leading to this migratory and invasive phenotype are thus essential. Accordingly, a genome-wide expression array analysis was performed on MPM cell lines and a set of 139 genes was identified as differentially expressed in cells with high versus low migratory activity. Reduced expression of the novel tumour suppressor integrin α7 (ITGA7) was found in highly motile cells. A significant negative correlation was observed between ITGA7 transcript levels and average displacement of cells. Forced overexpression of ITGA7 in MPM cells with low endogenous ITGA7 expression inhibited cell motility, providing direct evidence for the regulatory role of ITGA7 in MPM cell migration. MPM cells showed decreased ITGA7 expressions at both transcription and protein levels when compared to non-malignant mesothelial cells. The majority of MPM cell cultures displayed hypermethylation of the ITGA7 promoter when compared to mesothelial cultures. A statistically significant negative correlation between ITGA7 methylation and ITGA7 expression was also observed in MPM cells. While normal human pleura samples unambiguously expressed ITGA7, a varying level of expression was found in a panel of 200 human MPM samples. In multivariate analysis, ITGA7 expression was found to be an independent prognostic factor. Although there was no correlation between histological subtypes and ITGA7 expression, importantly, patients with high tumour cell ITGA7 expression had an increased median overall survival compared to the low- or no-expression groups (463 versus 278 days). In conclusion, our data suggest that ITGA7 is an epigenetically regulated tumour suppressor gene and a prognostic factor in human MPM.

7 Article Ki67 index is an independent prognostic factor in epithelioid but not in non-epithelioid malignant pleural mesothelioma: a multicenter study. 2015

Ghanim, B / Klikovits, T / Hoda, M A / Lang, G / Szirtes, I / Setinek, U / Rozsas, A / Renyi-Vamos, F / Laszlo, V / Grusch, M / Filipits, M / Scheed, A / Jakopovic, M / Samarzija, M / Brcic, L / Stancic-Rokotov, D / Kern, I / Rozman, A / Dekan, G / Klepetko, W / Berger, W / Glasz, T / Dome, B / Hegedus, B. ·1] Department of Surgery, Comprehensive Cancer Center, Division of Thoracic Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria [2] Institute of Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria. · Department of Surgery, Comprehensive Cancer Center, Division of Thoracic Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. · 1] Department of Surgery, Comprehensive Cancer Center, Division of Thoracic Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria [2] Department of Thoracic Surgery, Semmelweis University, 1085 Budapest, Hungary. · 2nd Institute of Pathology, Semmelweis University, 1085 Budapest, Hungary. · Division of Pathology, Otto Wagner Hospital, 1145 Vienna Austria. · 1] Department of Surgery, Comprehensive Cancer Center, Division of Thoracic Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria [2] National Koranyi Institute of TB and Pulmonology, 1121 Budapest, Hungary. · 1] Department of Surgery, Comprehensive Cancer Center, Division of Thoracic Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria [2] National Institute of Oncology, 1525 Budapest, Hungary. · Institute of Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria. · Department for Respiratory Diseases Jordanovac, School of Medicine, University of Zagreb, University Hospital Center, 10 000 Zagreb, Croatia. · Institute of Pathology, School of Medicine, University of Zagreb, 10 000 Zagreb, Croatia. · Department of Thoracic Surgery, University of Zagreb, 10 000 Zagreb, Croatia. · University Clinic of Respiratory and Allergic Diseases, 4204 Golnik, Slovenia. · Department of Pathology, Medical University of Vienna, 1090 Vienna, Austria. · 1] 2nd Institute of Pathology, Semmelweis University, 1085 Budapest, Hungary [2] National Koranyi Institute of TB and Pulmonology, 1121 Budapest, Hungary. · 1] Department of Surgery, Comprehensive Cancer Center, Division of Thoracic Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria [2] Department of Thoracic Surgery, Semmelweis University, 1085 Budapest, Hungary [3] National Koranyi Institute of TB and Pulmonology, 1121 Budapest, Hungary [4] National Institute of Oncology, 1525 Budapest, Hungary. · 1] Department of Surgery, Comprehensive Cancer Center, Division of Thoracic Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria [2] MTA-SE Molecular Oncology Research Group, Hungarian Academy of Sciences, 1091 Budapest, Hungary. ·Br J Cancer · Pubmed #25633038.

ABSTRACT: BACKGROUND: Estimating the prognosis in malignant pleural mesothelioma (MPM) remains challenging. Thus, the prognostic relevance of Ki67 was studied in MPM. METHODS: Ki67 index was determined in a test cohort of 187 cases from three centres. The percentage of Ki67-positive tumour cells was correlated with clinical variables and overall survival (OS). The prognostic power of Ki67 index was compared with other prognostic factors and re-evaluated in an independent cohort (n=98). RESULTS: Patients with Ki67 higher than median (>15%) had significantly (P<0.001) shorter median OS (7.5 months) than those with low Ki67 (19.1 months). After multivariate survival analyses, Ki67 proved to be-beside histology and treatment-an independent prognostic marker in MPM (hazard ratio (HR): 2.1, P<0.001). Interestingly, Ki67 was prognostic exclusively in epithelioid (P<0.001) but not in non-epithelioid subtype. Furthermore, Ki67 index was significantly lower in post-chemotherapy samples when compared with chemo-naive cases. The prognostic power was comparable to other recently published prognostic factors (CRP, fibrinogen, neutrophil-to-leukocyte ratio (NLR) and nuclear grading score) and was recapitulated in the validation cohort (P=0.048). CONCLUSION: This multicentre study demonstrates that Ki67 is an independent and reproducible prognostic factor in epithelioid but not in non-epithelioid MPM and suggests that induction chemotherapy decreases the proliferative capacity of MPM.

8 Article Reproducibility of histological subtyping of malignant pleural mesothelioma. 2014

Brčić, Luka / Jakopović, Marko / Brčić, Iva / Klarić, Vlasta / Milošević, Milan / Sepac, Ana / Samaržija, Miroslav / Seiwerth, Sven. ·Institute of Pathology, University of Zagreb School of Medicine, Salata 10, 10000, Zagreb, Croatia, lbrcic@mef.hr. ·Virchows Arch · Pubmed #25300229.

ABSTRACT: Malignant pleural mesothelioma (MPM) has a very poor prognosis. Although clinical stage is currently the only reliable prognostic factor, histologic subtyping reportedly also affects prognosis. Some studies propose reclassification of pleomorphic epithelioid as biphasic or sarcomatoid MPM. This study assessed prognostic significance and interobserver agreement in MPM subtyping of small biopsy specimens. We analyzed biopsy specimens, and clinical and survival data from records of 108 patients who were diagnosed between 2000 and 2010 at the Institute of Pathology University of Zagreb School of Medicine, of whom 98 had epithelioid MPM, six biphasic MPM, and four sarcomatoid MPM. Among epithelioid subtypes, 44 (44.9 %) were solid, 19 (19.4 %) tubulopapillary, 18 (18.4 %) acinar, six (6.1 %) adenomatoid, five (5.1 %) pleomorphic, four (4.1 %) trabecular, and two (2.0 %) micropapillary subtype. Interobserver reliability for histological diagnosis was found to be κ = 0.72 (P < 0.001). Median overall survival for epithelioid MPM was 10.5 months with an interquartile range (IQR) of 5.8-28.0 months but significantly shorter for the pleomorphic subtype (3 [IQR 3.0-8.0] months; P = 0.034), but not significantly different from biphasic (6.5 [IQR 3.5-15.3] months) and sarcomatoid mesothelioma (4.0 [IQR 1.3-6.8] months; P = 0.270). We found strong reproducibility of MPM subtyping with good interobserver agreement. Furthermore, our results indicate that pleomorphic subtype to be a predictor of poor prognosis and support classifying it with sarcomatoid or biphasic MPM, as patients with the pleomorphic, biphasic, or sarcomatoid subtype show similarly poor overall survival.

9 Article Circulating fibrinogen is a prognostic and predictive biomarker in malignant pleural mesothelioma. 2014

Ghanim, B / Hoda, M A / Klikovits, T / Winter, M-P / Alimohammadi, A / Grusch, M / Dome, B / Arns, M / Schenk, P / Jakopovic, M / Samarzija, M / Brcic, L / Filipits, M / Laszlo, V / Klepetko, W / Berger, W / Hegedus, B. ·1] Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna 1090, Vienna, Austria [2] Institute of Cancer Research, Department of Internal Medicine I, Medical University of Vienna 1090, Vienna, Austria. · Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna 1090, Vienna, Austria. · Institute of Cancer Research, Department of Internal Medicine I, Medical University of Vienna 1090, Vienna, Austria. · 1] Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna 1090, Vienna, Austria [2] National Koranyi Institute of Pulmonology, Budapest 1121, Hungary [3] Department of Thoracic Surgery, National Institute of Oncology, Budapest, Hungary. · Department of Pulmonology, LKH Hochegg, 2803 Vienna, Austria. · University of Zagreb, School of Medicine, Department for Respiratory Diseases Jordanovac, University Hospital Center, Zagreb 10000, Croatia. · University of Zagreb, School of Medicine, Institute of Pathology, Zagreb 10000, Croatia. · 1] Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna 1090, Vienna, Austria [2] Department of Biological Physics, Eötvös University, Budapest 1117, Hungary. · 1] Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna 1090, Vienna, Austria [2] Institute of Cancer Research, Department of Internal Medicine I, Medical University of Vienna 1090, Vienna, Austria [3] MTA-SE Molecular Oncology Research Group, Hungarian Academy of Sciences, Budapest 1091, Hungary. ·Br J Cancer · Pubmed #24434429.

ABSTRACT: BACKGROUND: To investigate the clinical utility of pretreatment plasma fibrinogen levels in malignant pleural mesothelioma (MPM) patients. METHODS: A retrospective multicenter study was performed in histologically proven MPM patients. All fibrinogen levels were measured at the time of diagnosis and clinical data were retrospectively collected after approval of the corresponding ethics committees. RESULTS: In total, 176 MPM patients (mean age: 63.5 years ± 10.4 years, 38 females and 138 males) were analysed. Most patients (n=154, 87.5%) had elevated (≥ 390 mg dl(-1)) plasma fibrinogen levels. When patients were grouped by median fibrinogen, patients with low level (≤ 627 mg dl(-1)) had significantly longer overall survival (OS) (19.1 months, confidence interval (CI) 14.5-23.7 months) when compared with those with high level (OS 8.5; CI 6.2-10.7 months). In multivariate survival analyses, fibrinogen was found to be an independent prognostic factor (hazard ratio 1.81, CI 1.23-2.65). Most interestingly, fibrinogen (cutoff 75th percentile per 750 mg dl(-1)) proved to be a predictive biomarker indicating treatment benefit achieved by surgery within multimodality therapy (interaction term: P=0.034). Accordingly, only patients below the 75th percentile benefit from surgery within multimodality therapy (31.3 vs 5.3 months OS). CONCLUSIONS: Fibrinogen is a novel independent prognostic biomarker in MPM. Most importantly, fibrinogen predicted treatment benefit achieved by surgery within multimodality therapy.

10 Minor In Reply. 2018

Brcic, Luka / Vlacic, Gregor / Quehenberger, Franz / Kern, Izidor. ·1  Institute of Pathology, Medical University of Graz, Graz, Austria. · 2  Cytology and Pathology Laboratory, University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia. · 3  Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria. ·Arch Pathol Lab Med · Pubmed #30407857.

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