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Melanoma: HELP
Articles by Mohammed Kashani-Sabet
Based on 59 articles published since 2008
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Between 2008 and 2019, M. Kashani-Sabet wrote the following 59 articles about Melanoma.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Guideline Melanoma. 2009

Coit, Daniel G / Andtbacka, Robert / Bichakjian, Christopher K / Dilawari, Raza A / Dimaio, Dominick / Guild, Valerie / Halpern, Allan C / Hodi, F Stephen / Kashani-Sabet, Mohammed / Lange, Julie R / Lind, Anne / Martin, Lainie / Martini, Mary C / Pruitt, Scott K / Ross, Merrick I / Sener, Stephen F / Swetter, Susan M / Tanabe, Kenneth K / Thompson, John A / Trisal, Vijay / Urist, Marshall M / Weber, Jeffrey / Wong, Michael K / Anonymous5080627. · ·J Natl Compr Canc Netw · Pubmed #19401060.

ABSTRACT: -- No abstract --

2 Editorial Tumor progression by immune evasion in melanoma: role of the programmed cell death-1/programmed cell death-1 ligand 1 interaction. 2010

Kashani-Sabet, Mohammed. · ·Cancer · Pubmed #20143442.

ABSTRACT: -- No abstract --

3 Review MicroRNA-mediated regulation of melanoma. 2014

Sun, V / Zhou, W B / Majid, S / Kashani-Sabet, M / Dar, A A. ·Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, 475 Brannan St Suite 220, San Francisco, CA, 94107, U.S.A. ·Br J Dermatol · Pubmed #24665835.

ABSTRACT: Melanoma is one of the most aggressive and deadly skin cancers, and, in its advanced stages, accounts for > 80% mortality. The incidence of melanoma is increasing worldwide; however, beyond surgical removal of the tumour, there is currently no curative therapy available, especially for its advanced stages. This may, in part, be owing to incomplete understanding of the molecular mechanisms that regulate the initiation and/or progression of melanoma to metastasis. The molecular mechanisms leading to the development and progression of melanoma are the focus of intense investigation, and many genetic/epigenetic alterations affecting melanoma progression and development have been identified. microRNAs (miRNAs) are emerging as important causal modulators in the development and progression of melanoma. The understanding of miRNA-mediated regulation of tumours has grown immensely over the last few years, as it has been understood to regulate most biological processes. Here, we review the currently available data on miRNAs associated with melanoma, highlighting those deregulated miRNAs that target important genes and pathways involved in the progression of melanocytes to primary and metastatic melanoma. We also review their potential clinical utility as biomarkers and potential use in targeted therapy.

4 Review Molecular markers in melanoma. 2014

Kashani-Sabet, M. ·Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, 475 Brannan St., Suite 220, San Francisco, CA, 94107, U.S.A. ·Br J Dermatol · Pubmed #23815339.

ABSTRACT: The last few years have witnessed the dawn of the molecular era in melanoma treatment. With the advent of successful therapy targeting mutant BRAF, melanoma is leading the field of cancer research in the molecular approach to therapy of advanced disease. Attempting to keep pace with advances in therapy are advances in the molecular assessment of melanoma progression, facilitated by the availability of genome-wide approaches to interrogate the malignant phenotype. At the DNA level, this has included approaches such as comparative genomic hybridization. At the RNA level, this has consisted of gene expression profiling using various assay methodologies. In certain instances, markers identified using these platforms have been further examined and developed using fluorescence in situ hybridization and immunohistochemical analysis. In this article, we will review recent progress in the development of novel molecular markers for melanoma that are nearing clinical application. We will review developments in the molecular classification of melanoma, in the molecular diagnosis of melanoma, and in the molecular assessment of melanoma prognosis.

5 Review Progression of cutaneous melanoma: implications for treatment. 2012

Leong, Stanley P L / Mihm, Martin C / Murphy, George F / Hoon, Dave S B / Kashani-Sabet, Mohammed / Agarwala, Sanjiv S / Zager, Jonathan S / Hauschild, Axel / Sondak, Vernon K / Guild, Valerie / Kirkwood, John M. ·Center for Melanoma Research and Treatment and Department of Surgery, California Pacific Medical Center, San Francisco, CA, USA. leongsx@cpmcri.org ·Clin Exp Metastasis · Pubmed #22892755.

ABSTRACT: The survival rates of melanoma, like any type of cancer, become worse with advancing stage. Spectrum theory is most consistent with the progression of melanoma from the primary site to the in-transit locations, regional or sentinel lymph nodes and beyond to the distant sites. Therefore, early diagnosis and surgical treatment before its spread is the most effective treatment. Recently, new approaches have revolutionized the diagnosis and treatment of melanoma. Genomic profiling and sequencing will form the basis for molecular taxonomy for more accurate subgrouping of melanoma patients in the future. New insights of molecular mechanisms of metastasis are summarized in this review article. Sentinel lymph node biopsy has become a standard of care for staging primary melanoma without the need for a more morbid complete regional lymph node dissection. With recent developments in molecular biology and genomics, novel molecular targeted therapy is being developed through clinical trials.

6 Review Cutaneous melanoma: a model to study cancer metastasis. 2011

Leong, Stanley P L / Gershenwald, Jeffrey E / Soong, Seng-Jaw / Schadendorf, Dirk / Tarhini, Ahmad A / Agarwala, Sanjiv / Hauschild, Axel / Soon, Christopher W M / Daud, Adil / Kashani-Sabet, Mohammed. ·Center for Melanoma Research and Treatment and Department of Surgery, California Pacific Medical Center and Research Institute, San Francisco, California 94115, USA. leongsx@cpmcri.org ·J Surg Oncol · Pubmed #21480247.

ABSTRACT: Nodal status in melanoma is a critically important prognostic factor for patient outcome. The survival rate drops to <10% when melanoma has spread beyond the regional lymph nodes and includes visceral involvement. In general, the process of melanoma metastasis is progressive in that dissemination of melanoma from the primary site to the regional lymph nodes occurs prior to systemic disease. The goal of this review article is to describe melanoma as a clinical model to study cancer metastasis. A future challenge is to develop a molecular taxonomy to subgroup melanoma patients at various stages of tumor progression for more accurate targeted treatment.

7 Review Patellar metastatic melanoma in a 13-year-old boy. 2010

Burk, Thomas F / Horvai, Andrew E / Gottschalk, Alexander R / Leong, Stanley P L / Kashani-Sabet, Mohammed / Goldsby, Robert E / Law, Jason / O'Donnell, Richard J. ·Department of Orthopaedic Surgery, University of California, San Francisco, USA. odonnelr@orthosurg.ucsf.edu ·Am J Orthop (Belle Mead NJ) · Pubmed #21720575.

ABSTRACT: The incidence of melanoma in US adults is approximately 1.5 per million, with 2% to 5% of patients developing metastatic disease. In children, melanoma is distinctly uncommon, and metastatic disease occurs even more seldom. This case report, the first of a patellar lesion as the initial presentation of metastatic melanoma in a pediatric patient, highlights use of patellectomy and intraoperative radiation therapy in obtaining palliative local control while avoiding periarticular functional morbidity.

8 Review Melanoma arising in African-, Asian-, Latino- and Native-American populations. 2009

Shoo, Brenda A / Kashani-Sabet, Mohammed. ·Melanoma Center, Department of Dermatology, University of California, San Francisco, CA 94153, USA. ·Semin Cutan Med Surg · Pubmed #19608060.

ABSTRACT: This review highlights melanoma trends observed among African-, Asian-, Latino- and Native-American populations. Melanoma is the most lethal form of skin cancer, accounting for about 75% of all skin cancer deaths. Generally, incidence rates increase with age, peak after age 40, and are greater in men than women. However, these trends do not reflect what is typically seen in minority ethnic groups, where incidence rates are lower. In addition, for some groups, relative disease-specific survival also is lower compared with European-Americans. Melanomas in minority populations also tend to appear in atypical locations and are of unclear etiology. To improve our understanding of the causes of melanoma arising in ethnic minority populations future research efforts are needed. In addition, the general lack of awareness of this disease entity among minority populations and the fact that certain ethnic groups tend to present with advanced disease further highlight the need for educational programs for both patients and health care professionals.

9 Clinical Trial Long-Term Survival after Complete Surgical Resection and Adjuvant Immunotherapy for Distant Melanoma Metastases. 2017

Faries, Mark B / Mozzillo, Nicola / Kashani-Sabet, Mohammed / Thompson, John F / Kelley, Mark C / DeConti, Ronald C / Lee, Jeffrey E / Huth, James F / Wagner, Jeffrey / Dalgleish, Angus / Pertschuk, Daniel / Nardo, Christopher / Stern, Stacey / Elashoff, Robert / Gammon, Guy / Morton, Donald L / Anonymous10680923. ·John Wayne Cancer Institute, Santa Monica, CA, USA. mfaries@theangelesclinic.org. · Istituto Nazionale dei Tumori de Napoli, Naples, Italy. · Mt. Zion Medical Center, University of California, San Francisco, San Francisco, CA, USA. · Royal Prince Alfred Hospital, Sydney, Australia. · Vanderbilt University, Nashville, TN, USA. · H. Lee Moffitt Cancer Center, Tampa, FL, USA. · MD Anderson Cancer Center, Houston, TX, USA. · Southwestern Medical Center at Dallas, University of Texas, Dallas, TX, USA. · Wagner & Associates, Indianapolis, IN, USA. · St. George's Hospital Medical School, London, Great Britain. · CancerVax Corp, Carlsbad, CA, USA. · John Wayne Cancer Institute, Santa Monica, CA, USA. · UCLA Life Sciences, Biomathematics, Los Angeles, CA, USA. ·Ann Surg Oncol · Pubmed #29019177.

ABSTRACT: BACKGROUND: This phase III study was undertaken to evaluate the efficacy of an allogeneic whole-cell vaccine (Canvaxin™) plus bacillus Calmette-Guerin (BCG) after complete resection of stage IV melanoma. METHODS: After complete resection of ≤5 distant metastases, patients were randomly assigned to BCG+Canvaxin (BCG/Cv) or BCG+placebo (BCG/Pl). The primary endpoint was overall survival (OS); secondary endpoints were disease-free survival (DFS), and immune response measured by skin test (ClinicalTrials.gov identifier: NCT00052156). RESULTS: Beginning in May 1998, 496 patients were randomized. In April 2005, the Data Safety Monitoring Board recommended stopping enrollment due to a low probability of efficacy. At that time, median OS and 5-year OS rate were 38.6 months and 44.9%, respectively, for BCG/Pl versus 31.4 months and 39.6% in the BCG/Cv group (hazard ratio (HR), 1.18; p = 0.250). Follow-up was extended at several trial sites through March 2010. Median OS and 5-year and 10-year survival was 39.1 months, 43.3 and 33.3%, respectively, for BCG/Pl versus 34.9 months, 42.5 and 36.4%, in the BCG/Cv group (HR 1.053; p = 0.696). Median DFS, 5- and 10-year DFS were 7.6 months, 23.8 and 21.7%, respectively, for BCG/Pl versus 8.5 months, 30.0%, and 30.0%, respectively, for the BCG/Cv group (HR 0.882; p = 0.260). Positive DTH skin testing correlated with increased survival. DISCUSSION: In this, the largest study of postsurgical adjuvant therapy for stage IV melanoma reported to date, BCG/Cv did not improve outcomes over BCG/placebo. Favorable long-term survival among study patients suggests that metastasectomy should be considered for selected patients with stage IV melanoma.

10 Clinical Trial The safety of and indications for immediate reconstruction of head and neck melanoma defects: our early experience. 2014

Parrett, Brian M / Kashani-Sabet, Mohammed / Leong, Stanley P L / Buncke, Neal / Singer, Mark I. ·From the *Buncke Clinic, and †Center for Melanoma Research and Treatment, California Pacific Medical Center, San Francisco, CA. ·Ann Plast Surg · Pubmed #24691340.

ABSTRACT: Melanoma excision requires wide margins, leaving large defects. Surgical dogma has taught that definitive reconstruction of melanoma defects be performed after permanent pathology results, with skin grafts favored. However, this results in an open wound and the need for a second operation. The advantages of immediate reconstruction with flaps are single-stage surgery, high patient satisfaction, no period of disfigurement, and cost savings. Our purpose was to evaluate rate of positive margins and local recurrence after immediate reconstruction of head and neck melanoma (HNM) defects with flaps to determine safety of this approach. We prospectively followed all patients with HNM treated at a single center from January 2010 to June 2012 and collected patient and tumor data and reconstruction type. Outcomes assessed were permanent pathology margins and local recurrence rate. Risk factors for positive margins were assessed. Seventy-six patients with HNM were treated with wide excision and immediate flap reconstruction with a mean age of 59 years. Five patients had melanoma in situ and 71 had invasive melanoma. There was a 15.4% ulceration rate. Median thickness for invasive melanoma was 2.2 mm. Mean excision margin was 1.4 cm. Median follow-up was 2 years; 5.3% of patients had positive margins on permanent pathology after reconstruction and 3 were reexcised with negative margins. Local recurrence rate was 2.6% with no recurrence in patients with previous reexcised positive margins. Significant risk factors for positive margins were melanoma in situ excised with 5-mm margins (P=0.012) and desmoplastic melanoma (P<0.02). Immediate flap reconstruction after excision of HNM can be safely performed with low positive margin and local recurrence rates. This should be offered to patients, especially those with primary melanomas with distinct borders and excision margins greater than or equal to 1 cm.

11 Clinical Trial Final trial report of sentinel-node biopsy versus nodal observation in melanoma. 2014

Morton, Donald L / Thompson, John F / Cochran, Alistair J / Mozzillo, Nicola / Nieweg, Omgo E / Roses, Daniel F / Hoekstra, Harold J / Karakousis, Constantine P / Puleo, Christopher A / Coventry, Brendon J / Kashani-Sabet, Mohammed / Smithers, B Mark / Paul, Eberhard / Kraybill, William G / McKinnon, J Gregory / Wang, He-Jing / Elashoff, Robert / Faries, Mark B / Anonymous4460784. ·The authors' affiliations are listed in the Appendix. ·N Engl J Med · Pubmed #24521106.

ABSTRACT: BACKGROUND: Sentinel-node biopsy, a minimally invasive procedure for regional melanoma staging, was evaluated in a phase 3 trial. METHODS: We evaluated outcomes in 2001 patients with primary cutaneous melanomas randomly assigned to undergo wide excision and nodal observation, with lymphadenectomy for nodal relapse (observation group), or wide excision and sentinel-node biopsy, with immediate lymphadenectomy for nodal metastases detected on biopsy (biopsy group). Results No significant treatment-related difference in the 10-year melanoma-specific survival rate was seen in the overall study population (20.8% with and 79.2% without nodal metastases). Mean (± SE) 10-year disease-free survival rates were significantly improved in the biopsy group, as compared with the observation group, among patients with intermediate-thickness melanomas, defined as 1.20 to 3.50 mm (71.3 ± 1.8% vs. 64.7 ± 2.3%; hazard ratio for recurrence or metastasis, 0.76; P=0.01), and those with thick melanomas, defined as >3.50 mm (50.7 ± 4.0% vs. 40.5 ± 4.7%; hazard ratio, 0.70; P=0.03). Among patients with intermediate-thickness melanomas, the 10-year melanoma-specific survival rate was 62.1 ± 4.8% among those with metastasis versus 85.1 ± 1.5% for those without metastasis (hazard ratio for death from melanoma, 3.09; P<0.001); among patients with thick melanomas, the respective rates were 48.0 ± 7.0% and 64.6 ± 4.9% (hazard ratio, 1.75; P=0.03). Biopsy-based management improved the 10-year rate of distant disease-free survival (hazard ratio for distant metastasis, 0.62; P=0.02) and the 10-year rate of melanoma-specific survival (hazard ratio for death from melanoma, 0.56; P=0.006) for patients with intermediate-thickness melanomas and nodal metastases. Accelerated-failure-time latent-subgroup analysis was performed to account for the fact that nodal status was initially known only in the biopsy group, and a significant treatment benefit persisted. CONCLUSIONS: Biopsy-based staging of intermediate-thickness or thick primary melanomas provides important prognostic information and identifies patients with nodal metastases who may benefit from immediate complete lymphadenectomy. Biopsy-based management prolongs disease-free survival for all patients and prolongs distant disease-free survival and melanoma-specific survival for patients with nodal metastases from intermediate-thickness melanomas. (Funded by the National Cancer Institute, National Institutes of Health, and the Australia and New Zealand Melanoma Trials Group; ClinicalTrials.gov number, NCT00275496.).

12 Article Microsatellitosis in Patients with Melanoma. 2019

Karakousis, Giorgos C / Gimotty, Phyllis A / Leong, Stanley P / Pockaj, Barbara A / White, Richard L / O'Donoghue, Cristina / Sinnamon, Andrew J / Bartlett, Edmund K / Dueck, Amylou C / Gould Rothberg, Bonnie E / Messina, Jane L / Vetto, John T / Sondak, Vernon K / Schneebaum, Schlomo / Kashani-Sabet, Mohammed / Han, Dale / Faries, Mark B / Zager, Jonathan S / Anonymous2571200. ·Hospital of the University of Pennsylvania, Philadelphia, PA, USA. giorgos.karakousis@uphs.upenn.edu. · Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA, USA. · California Pacific Medical Center and Research Institute, San Francisco, CA, USA. · Mayo Clinic, Phoenix, AZ, USA. · Carolinas Medical Center, Charlotte, NC, USA. · Department of Surgery, Rush Medical College, Chicago, IL, USA. · Hospital of the University of Pennsylvania, Philadelphia, PA, USA. · Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Yale University School of Medicine, New Haven, CT, USA. · Moffitt Cancer Center, Tampa, FL, USA. · Oregon Health and Science University, Portland, OR, USA. · Ichilov Hospital, Tel Aviv, Israel. · Angeles Clinic and Research Institute, Los Angeles, CA, USA. ·Ann Surg Oncol · Pubmed #30421045.

ABSTRACT: BACKGROUND: Microsatellitosis (mS) in melanoma has been considered a marker of unfavorable tumor biology, leading to the current American Joint Committee on Cancer staging of IIIB/C/D disease, despite few investigative studies of this entity limited by the small sample sizes and incomplete nodal microstaging. We sought to better characterize outcomes and prognostic factors in a multi-institutional cohort of patients with mS and nodal microstaging. METHODS: The Sentinel Lymph Node Working Group cohort included 414 mS patients who underwent sentinel lymph node (SLN) biopsy. Cox regression analysis was used to evaluate the prognostic significance of established clinicopathologic characteristics. Melanoma-specific survival (MSS) of patients with mS was compared with 3002 similarly staged patients from the Surveillance, Epidemiology, and End Results (SEER) Program registry. RESULTS: The median age of the mS cohort was 64.9 years; 39.6% were female. Median thickness was 3 mm, 40.6% of cases were ulcerated, and the SLN positivity rate was 46.7%. Increasing thickness, male sex, and SLN positivity were significantly associated with poorer MSS. Stage IIIB/C/D 5-year MSS rates were 86.3% (95% confidence interval [CI] 79.4-93.3%), 54.1% (95% CI 45.4-59.7%), and 44.2% (95% CI 25.4-63.0%), respectively. MSS survival for the stage IIIB mS cohort was significantly better than a similarly staged SEER cohort (5-year MSS of 70.1%, 95% CI 66.0-74.2%), while no significant difference was observed for the stage IIIC or D cohorts. CONCLUSIONS: SLN metastases are common and are a significant prognostic factor in patients with mS. Survival in stage IIIB patients with mS was considerably more favorable than their stage would otherwise suggest, which has important implications for decisions regarding adjuvant therapy for patients with mS.

13 Article Intraoperative Imaging with a Portable Gamma Camera May Reduce the False-Negative Rate for Melanoma Sentinel Lymph Node Surgery. 2018

Leong, Stanley P / Wu, Max / Lu, Ying / Torre, Donald M / von Bakonyi, Anna / Ospina, Arianna M / Newsom, James D / Luckett, William S / Soon, Christopher W / Kim, Kevin B / Kashani-Sabet, Mohammed. ·California Pacific Medical Center, San Francisco, CA, USA. leongsx@cpmcri.org. · California Pacific Medical Center, San Francisco, CA, USA. · Stanford University, Stanford, CA, USA. ·Ann Surg Oncol · Pubmed #30105436.

ABSTRACT: BACKGROUND: Preoperative imaging and intraoperative gamma probe (GP) localization is standard for identifying sentinel lymph nodes (SLNs) in melanoma patients. The aim of this prospective Institutional Review Board-approved study was to investigate whether an intraoperative portable gamma camera (PGC) improves SLN detection over the GP. METHODS: Lymphoscintigraphy and single photon emission computed tomography/computed tomography were performed after injection of 99mTc-Tilmanocept in melanoma patients (≥ 18 years, Breslow thickness ≥ 1.0 mm). A GP was used to localize the SLNs in each basin, which was explored by the GP to ensure that the operative field was < 10% counts of the hottest SLN. The PGC was then used after a negative GP screening. Any residual hotspots identified by the PGC were considered as additional SLNs and were removed following the 10% rule. RESULTS: Preoperative imaging of 100 patients identified 138 SLN basins, with 306 SLNs being identified by conventional surgery. The PGC localized 89 additional SLNs in 54 patients. Thus, the PGC identified an additional 23% of SLNs [95% confidence interval (CI) 18-27%]. Four of these 89 SLNs showed micrometastasis in four patients, in two of whom the only tumor-positive SLN was identified by the PGC, preventing two false-negative cases. Thus, the null hypothesis that the PGC did not detect additional positive SLNs was rejected (p = 0.000). The overall SLN positive rate was 9.9% (39/395, 95% CI 6-12), and the overall patient positive rate was increased using the PGC, from 25 to 27% (27/100). CONCLUSIONS: Intraoperative PGC imaging yielded additional SLNs in a significant number of patients over GP alone. Identification of these additional SLNs resulted in upstaging of four patients with two patients being converted from a negative to a positive status, thus, preventing two false-negative cases.

14 Article PHIP as a therapeutic target for driver-negative subtypes of melanoma, breast, and lung cancer. 2018

de Semir, David / Bezrookove, Vladimir / Nosrati, Mehdi / Dar, Altaf A / Wu, Clayton / Shen, Julia / Rieken, Christopher / Venkatasubramanian, Meenakshi / Miller, James R / Desprez, Pierre-Yves / McAllister, Sean / Soroceanu, Liliana / Debs, Robert J / Salomonis, Nathan / Schadendorf, Dirk / Cleaver, James E / Kashani-Sabet, Mohammed. ·California Pacific Medical Center Research Institute, San Francisco, CA 94107. · Carl Zeiss Microscopy, LLC, New York, NY 10594. · Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229. · Department of Dermatology, University of Duisburg-Essen, D-45147 Essen, Germany. · German Cancer Consortium, 69120 Heidelberg, Germany. · Department of Dermatology and Pharmaceutical Chemistry, University of California San Francisco, CA 94121 james.cleaver@ucsf.edu kashani@cpmcri.org. · California Pacific Medical Center Research Institute, San Francisco, CA 94107; james.cleaver@ucsf.edu kashani@cpmcri.org. ·Proc Natl Acad Sci U S A · Pubmed #29866840.

ABSTRACT: The identification and targeting of key molecular drivers of melanoma and breast and lung cancer have substantially improved their therapy. However, subtypes of each of these three common, lethal solid tumors lack identified molecular drivers, and are thus not amenable to targeted therapies. Here we show that pleckstrin homology domain-interacting protein (PHIP) promotes the progression of these "driver-negative" tumors. Suppression of PHIP expression significantly inhibited both tumor cell proliferation and invasion, coordinately suppressing phosphorylated AKT, cyclin D1, and talin1 expression in all three tumor types. Furthermore, PHIP's targetable bromodomain is functional, as it specifically binds the histone modification H4K91ac. Analysis of TCGA profiling efforts revealed PHIP overexpression in triple-negative and basal-like breast cancer, as well as in the bronchioid subtype of nonsmall cell lung cancer. These results identify a role for PHIP in the progression of melanoma and breast and lung cancer subtypes lacking identified targeted therapies. The use of selective, anti-PHIP bromodomain inhibitors may thus yield a broad-based, molecularly targeted therapy against currently nontargetable tumors.

15 Article Survival and clinical outcomes of patients with melanoma brain metastasis in the era of checkpoint inhibitors and targeted therapies. 2018

Vosoughi, Elham / Lee, Jee Min / Miller, James R / Nosrati, Mehdi / Minor, David R / Abendroth, Roy / Lee, John W / Andrews, Brian T / Leng, Lewis Z / Wu, Max / Leong, Stanley P / Kashani-Sabet, Mohammed / Kim, Kevin B. ·Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, 2100 Webster Street, Suite 326, San Francisco, CA, 94115, USA. · Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, 2100 Webster Street, Suite 326, San Francisco, CA, 94115, USA. KimKB@sutterhealth.org. ·BMC Cancer · Pubmed #29703161.

ABSTRACT: BACKGROUND: Melanoma brain metastasis is associated with an extremely poor prognosis, with a median overall survival of 4-5 months. Since 2011, the overall survival of patients with stage IV melanoma has been significantly improved with the advent of new targeted therapies and checkpoint inhibitors. We analyze the survival outcomes of patients diagnosed with brain metastasis after the introduction of these novel drugs. METHODS: We performed a retrospective analysis of our melanoma center database and identified 79 patients with brain metastasis between 2011 and 2015. RESULTS: The median time from primary melanoma diagnosis to brain metastasis was 3.2 years. The median overall survival duration from the time of initial brain metastasis was 12.8 months. Following a diagnosis of brain metastasis, 39 (49.4%), 28 (35.4%), and 24 (30.4%) patients were treated with anti-CTLA-4 antibody, anti-PD-1 antibody, or BRAF inhibitors (with or without a MEK inhibitor), with a median overall survival of 19.2 months, 37.9 months and 12.7 months, respectively. Factors associated with significantly reduced overall survival included male sex, cerebellar metastasis, higher number of brain lesions, and treatment with whole-brain radiation therapy. Factors associated with significantly longer overall survival included treatment with craniotomy, stereotactic radiosurgery, or with anti-PD-1 antibody after initial diagnosis of brain metastasis. CONCLUSIONS: These results show a significant improvement in the overall survival of patients with melanoma brain metastasis in the era of novel therapies. In addition, they suggest the activity of anti-PD-1 therapy specifically in the setting of brain metastasis.

16 Article Stratifying SLN incidence in intermediate thickness melanoma patients. 2018

Chang, James M / Kosiorek, Heidi E / Dueck, Amylou C / Leong, Stanley P L / Vetto, John T / White, Richard L / Avisar, Eli / Sondak, Vernon K / Messina, Jane L / Zager, Jonathan S / Garberoglio, Carlos / Kashani-Sabet, Mohammed / Pockaj, Barbara A. ·Department of Surgery, Mayo Clinic Arizona, Phoenix, AZ, USA. · Section of Biostatistics, Mayo Clinic Arizona, Phoenix, AZ, USA. · Center for Melanoma Research and Treatment, Department of Surgery, California Pacific Medical Center, San Francisco, CA, USA. · Department of Surgery, Oregon Health & Science University, Portland, OR, USA. · Department of Surgery, Levine Cancer Institute, Carolinas Medical Center, Charlotte, NC, USA. · Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA. · Departments of Cutaneous Oncology and Sarcoma, Moffitt Cancer Center, Tampa, FL, USA. · Department of Surgery, Loma Linda University School of Medicine, Loma Linda, CA, USA. · Department of Surgery, Mayo Clinic Arizona, Phoenix, AZ, USA. Electronic address: pockaj.barbara@mayo.edu. ·Am J Surg · Pubmed #29502857.

ABSTRACT: BACKGROUND: Guidelines for melanoma recommend sentinel lymph node biopsy (SLNB) in patients with melanomas ≥1 mm thickness. Recent single institution studies have found tumors <1.5 mm a low-risk group for positive SLNB. METHODS: A retrospective review of the Sentinel Lymph Node Working Group multicenter database identified patients with intermediate thickness melanoma (1.01-4.00 mm) who had SLNB, and assessed predictors for positive SLNB. RESULTS: 3460 patients were analyzed, 584 (17%) had a positive SLNB. Univariate factors associated with a positive SLNB included age <60 (p < .001), tumor on the trunk/lower extremity (p < .001), Breslow depth ≥2 mm (p < .001), ulceration (p < .001), mitotic rate ≥1/mm CONCLUSIONS: Intermediate thickness melanoma has significant heterogeneity of SLNB positivity. Low-risk subgroups can be found among older patients in the absence of high-risk features.

17 Article Prospective Validation of Molecular Prognostic Markers in Cutaneous Melanoma: A Correlative Analysis of E1690. 2017

Kashani-Sabet, Mohammed / Nosrati, Mehdi / Miller, James R / Sagebiel, Richard W / Leong, Stanley P L / Lesniak, Andrew / Tong, Schuyler / Lee, Sandra J / Kirkwood, John M. ·Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, San Francisco, California. kashani@cpmcri.org. · Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, San Francisco, California. · Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania. · Dana-Farber Cancer Institute, Boston, Massachusetts. · ECOG-ACRIN Melanoma Committee, Philadelphia, Pennsylvania. · University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania. ·Clin Cancer Res · Pubmed #28790109.

ABSTRACT:

18 Article Is the non-sentinel lymph node compartment the next site for melanoma progression from the sentinel lymph node compartment in the regional nodal basin? 2017

Rios-Cantu, Andrei / Lu, Ying / Melendez-Elizondo, Victor / Chen, Michael / Gutierrez-Range, Alejandra / Fadaki, Niloofar / Thummala, Suresh / West-Coffee, Carla / Cleaver, James / Kashani-Sabet, Mohammed / Leong, Stanley P L. ·Center for Melanoma Research & Treatment, California Pacific Medical Center, 2340 Clay Street, 2nd Floor, San Francisco, CA, 94115, USA. · Universidad Autonoma de Nuevo Leon, Monterrey, Nuevo Leon, Mexico. · Consorcio de Universidades Mexicanas (CuMEX), Pachuca, Mexico. · Departments of Biomedical Data Science, Health Research and Policy, and Radiology, The Stanford Cancer Institute, Stanford University, Stanford, CA, USA. · University of Nevada, Las Vegas, Las Vegas, NV, USA. · Department of Dermatology, University of California, San Francisco, CA, USA. · Center for Melanoma Research & Treatment, California Pacific Medical Center, 2340 Clay Street, 2nd Floor, San Francisco, CA, 94115, USA. leongsx@cpmcri.org. ·Clin Exp Metastasis · Pubmed #28699042.

ABSTRACT: Melanoma patients with additional positive lymph nodes in the completion lymph node dissection (CLND) following a positive sentinel lymph node (SLN) biopsy would have a poorer prognosis than patients with no additional positive lymph nodes. We hypothesize that the progression of disease from the SLN to the non-SLN compartment is orderly and is associated with the worsening of the disease status. Thus, the SLN and non-SLN compartments are biologically different in that cancer cells, in general, arrive in the SLN compartment before spreading to the non-SLN compartment. To validate this concept, we used a large cohort of melanoma patients from our prospective SLN database in an academic tertiary medical center. Adult cutaneous melanoma patients (n = 291) undergoing CLND after a positive SLN biopsy from 1994 to 2009 were analyzed. Comparison of 5-year disease-free survival and 5-year overall survival between positive (n = 66) and negative (n = 225) CLND groups was made. The 5-year disease-free survival rates were 55% (95% CI 49-62%) for patients with no additional LN on CLND versus 14% (95% CI 8-26%) in patients with positive LN on CLND (p < 0.0001, log-rank test). The median disease-free survival time was 7.4 years with negative CLND (95% CI 4.4-15+ years) and 1.2 years with positive CLND (95% CI 1.0-1.8 years). The 5-year overall survival rates were 67% (95% CI 61-74%) for negative CLND versus 38% (95% CI 28-52%) for positive CLND (p < 0.0001, log-rank test). The median overall survival time was 12.1 years for negative CLND (95% CI 9.3-15+ years) and 2.5 years for positive CLND (95% CI 2.2-5.7 years). This study shows that CLND status is a significant prognostic factor for patients with positive SLNs undergoing CLND. Also, it suggests an orderly progression of metastasis from the SLN to the non-SLN compartment. Thus, the SLN in the regional nodal basin draining the primary melanoma may serve as an important gateway for metastasis to the non-SLN compartment and beyond to the systemic sites.

19 Article Is pelvic sentinel node biopsy necessary for lower extremity and trunk melanomas? 2017

Schuitevoerder, Darryl / Leong, Stanley P L / Zager, Jonathan S / White, Richard L / Avisar, Eli / Kosiorek, Heidi / Dueck, Amylou / Fortino, Jeanine / Kashani-Sabet, Mohammed / Hart, Kyle / Vetto, John T. ·Department of Surgery, Oregon Health & Science University, Portland, OR, USA. Electronic address: schuitev@ohsu.edu. · Center for Melanoma Research and Treatment, Department of Surgery, California Pacific Medical Center, San Francisco, CA, USA. · Departments of Cutaneous Oncology and Sarcoma, Moffitt Cancer Center, Tampa, FL, USA. · Department of Surgery, Levine Cancer Institute, Carolinas Medical Center, Charlotte, NC, USA. · Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA. · Section of Biostatistics, Mayo Clinic Arizona, Phoenix, AZ, USA. · Department of Surgery, Division of Surgical Oncology, Oregon Health & Science University, Portland, OR, USA. · Department of Surgery, Oregon Health & Science University, Portland, OR, USA. ·Am J Surg · Pubmed #28411863.

ABSTRACT: OBJECTIVE: There is currently no consensus regarding how to address pelvic sentinel lymph nodes (PSLNs) in melanoma. Thus, our objectives were to identify the incidence and clinical impact of PSLNs. METHODS: Retrospective review of a prospectively collected multi-institutional melanoma database. RESULTS: Of 2476 cases of lower extremity and trunk melanomas, 227 (9%) drained to PSLNs (181 to both PSLNs and superficial (inguinal or femoral) sentinel lymph nodes (SSLN) and 46 to PSLNs alone). Seventeen (7.5%) of 227 PSLN cases were positive for nodal metastasis, 8 of which drained to PSLNs only while 9 drained to both PSLNs and SSLNs. Complication rates between PSLN and SSLN biopsy were similar (15% vs. 14% respectively). In 181 cases with drainage to both SSLNs and PSLNs, PSLN biopsy upstaged one patient (0.6%), and completion dissection based on a positive PSLN did not upstage any. CONCLUSIONS: PSLN biopsy is safe, however in the setting of negative SSLNs there is minimal clinical impact. We therefore recommend PSLN biopsy when the SSLNs are positive or when the tumor drains to PSLNs alone.

20 Article The Impact of Smoking on Sentinel Node Metastasis of Primary Cutaneous Melanoma. 2017

Jones, Maris S / Jones, Peter C / Stern, Stacey L / Elashoff, David / Hoon, Dave S B / Thompson, John / Mozzillo, Nicola / Nieweg, Omgo E / Noyes, Dirk / Hoekstra, Harald J / Zager, Jonathan S / Roses, Daniel F / Testori, Alessandro / Coventry, Brendon J / Smithers, Mark B / Andtbacka, Robert / Agnese, Doreen / Schultz, Erwin / Hsueh, Eddy C / Kelley, Mark / Schneebaum, Schlomo / Jacobs, Lisa / Bowles, Tawnya / Kashani-Sabet, Mohammed / Johnson, Douglas / Faries, Mark B. ·Division of Surgical Oncology, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USA. · Department of Molecular Oncology, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USA. · Department of Biostatistics, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USA. · UCLA Department of Biostatistics, Los Angeles, CA, USA. · Melanoma Institute Australia, Sydney, NSW, Australia. · Istituto Nazionale dei Tumori Napoli, Napoli, Italy. · IHC Cancer Services, Intermountain Medical Center, Salt Lake City, UT, USA. · Universitair Medisch Centrum Groningen, Groningen, The Netherlands. · H. Lee Moffitt Cancer Center, Tampa, USA. · NYU Langone Medical Center, New York, USA. · Istituto Europeo di Oncologia, Milano, Italy. · Royal Adelaide Hospital Discipline of Surgery, Royal Adelaide HospitalUniversity of Adelaide, Adelaide, SA, Australia. · Princess Alexandra Hospital, Woolloongabba, Queensland, Australia. · Huntsman Cancer Institute, Salt Lake City, USA. · Ohio State University, Columbus, USA. · Nuremberg General Hospital - Paracelsus Medical University, Nuremberg, Germany. · Saint Louis University, St. Louis, USA. · Vanderbilt University, Nashville, USA. · Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel. · Johns Hopkins Medical Institute, Baltimore, USA. · California Pacific Medical Center, San Francisco, USA. · Department of Melanoma Research, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USA. mark.faries@jwci.org. ·Ann Surg Oncol · Pubmed #28224364.

ABSTRACT: BACKGROUND: Although a well-established causative relationship exists between smoking and several epithelial cancers, the association of smoking with metastatic progression in melanoma is not well studied. We hypothesized that smokers would be at increased risk for melanoma metastasis as assessed by sentinel lymph node (SLN) biopsy. METHODS: Data from the first international Multicenter Selective Lymphadenectomy Trial (MSLT-I) and the screening-phase of the second trial (MSLT-II) were analyzed to determine the association of smoking with clinicopathologic variables and SLN metastasis. RESULTS: Current smoking was strongly associated with SLN metastasis (p = 0.004), even after adjusting for other predictors of metastasis. Among 4231 patients (1025 in MSLT-I and 3206 in MSLT-II), current or former smoking was also independently associated with ulceration (p < 0.001 and p < 0.001, respectively). Compared with current smoking, never smoking was independently associated with decreased Breslow thickness in multivariate analysis (p = 0.002) and with a 0.25 mm predicted decrease in thickness. CONCLUSION: The direct correlation between current smoking and SLN metastasis of primary cutaneous melanoma was independent of its correlation with tumor thickness and ulceration. Smoking cessation should be strongly encouraged among patients with or at risk for melanoma.

21 Article BPTF transduces MITF-driven prosurvival signals in melanoma cells. 2016

Dar, Altaf A / Majid, Shahana / Bezrookove, Vladimir / Phan, Binh / Ursu, Sarah / Nosrati, Mehdi / De Semir, David / Sagebiel, Richard W / Miller, James R / Debs, Robert / Cleaver, James E / Kashani-Sabet, Mohammed. ·Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, San Francisco, CA 94107; · Department of Urology, Veterans Affairs Medical Center, University of California, San Francisco, CA 94121; · Department of Dermatology and Pharmaceutical Chemistry, University of California, San Francisco, CA 94143 JCleaver@cc.ucsf.edu kashani@cpmcri.org. · Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, San Francisco, CA 94107; JCleaver@cc.ucsf.edu kashani@cpmcri.org. ·Proc Natl Acad Sci U S A · Pubmed #27185926.

ABSTRACT: Microphthalmia-associated transcription factor (MITF) plays a critical and complex role in melanocyte transformation. Although several downstream targets of MITF action have been identified, the precise mechanisms by which MITF promotes melanocytic tumor progression are incompletely understood. Recent studies identified an oncogenic role for the bromodomain plant homeodomain finger transcription factor (BPTF) gene in melanoma progression, in part through activation of BCL2, a canonical target of MITF signaling. Analysis of the BPTF promoter identified a putative MITF-binding site, suggesting that MITF may regulate BPTF expression. Overexpression of MITF resulted in up-regulation of BPTF in a panel of melanoma and melanocyte cell lines. shRNA-mediated down-regulation of MITF in melanoma cells was accompanied by down-regulation of BPTF and BPTF-regulated genes (including BCL2) and resulted in reduced proliferative capacity of melanoma cells. The suppression of cell growth mediated by MITF silencing was rescued by overexpression of BPTF cDNA. Binding of MITF to the BPTF promoter was demonstrated using ChIP analysis. MITF overexpression resulted in direct transcriptional activation of BPTF, as evidenced by increased luciferase activity driven by the BPTF promoter. These results indicate that BPTF transduces key prosurvival signals driven by MITF, further supporting its important role in promoting melanoma cell survival and progression.

22 Article Selective Sentinel Lymph Node Dissection in Lower Extremity Melanoma. 2016

Miranda, Suzette G / Parrett, Brian M / Li, Rui Rachel / Lee, Grant / Chang, Tiffany / Fadaki, Niloofar / Cardona-Huerta, Servando / Cleaver, James E / Kashani-Sabet, Mohammed / Leong, Stanley P. ·San Francisco, Calif. From The Buncke Clinic, California Pacific Medical Center; the Departments of Surgery and Dermatology, University of California, San Francisco; Medivation Biostatistics; and the Center for Melanoma Research & Treatment, California Pacific Medical Center & Research Institute. ·Plast Reconstr Surg · Pubmed #26809037.

ABSTRACT: BACKGROUND: There is debate as to whether deep inguinal lymph nodes should be removed with the superficial or femoral lymph nodes during sentinel lymph node biopsy for lower extremity melanoma, when both superficial and deep inguinal lymph nodes are identified by preoperative lymphoscintigraphy. This study evaluated the lymphatic drainage patterns in lower extremity melanoma to determine whether certain patterns could be used to limit the level of node removal and define the extent of dissection. METHODS: A retrospective outcomes review was performed of lower extremity melanoma patients with excision and sentinel lymph node biopsy from 1995 to 2010. Outcomes included location of sentinel lymph node drainage basins, sentinel lymph node-positivity, and disease-free and overall survival, with drainage patterns compared between above- and below-knee melanomas. RESULTS: Of 499 patients with lower extremity melanoma having sentinel lymph node biopsy, 356 had below-the-knee and 143 had above-the-knee melanoma. For below-knee melanoma, the node-positivity rate was 23 percent (63 of 271) for superficial inguinal, 0 percent (zero of three) for deep inguinal, and 50 percent (one of two) for popliteal basins. For above-knee melanoma, the positivity rate was 21 percent (24 of 113) for superficial inguinal, 33 percent (one of three) for deep inguinal basins, and 0 percent (zero of zero) for popliteal basins. Importantly, no patients with a negative superficial inguinal sentinel lymph node had a positive deep inguinal sentinel lymph node on final pathologic evaluation [corrected]. CONCLUSIONS: A difference was noted in patterns of sentinel lymph node drainage from lower extremity melanoma below and above the knee. Biopsy for deep inguinal basins may be deferred if there is simultaneous drainage to the superficial inguinal basin by preoperative lymphoscintigraphy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

23 Article The role of BPTF in melanoma progression and in response to BRAF-targeted therapy. 2015

Dar, Altaf A / Nosrati, Mehdi / Bezrookove, Vladimir / de Semir, David / Majid, Shahana / Thummala, Suresh / Sun, Vera / Tong, Schuyler / Leong, Stanley P L / Minor, David / Billings, Paul R / Soroceanu, Liliana / Debs, Robert / Miller, James R / Sagebiel, Richard W / Kashani-Sabet, Mohammed. ·Center for Melanoma Research and Treatment (AAD, MN, VB, DdS, ST, VS, ST, SPLL, DM, JRMIII, RWS, MKS), California Pacific Medical Center Research Institute, San Francisco, CA (AAD, MN, VB, DdS, ST, VS, ST, SPLL, DM, LS, RD, JRMIII, RWS, MKS) · Department of Urology, Veterans Affairs Medical Center and University of California San Francisco, San Francisco, CA (SM) · Life Technologies, Inc. Carlsbad, CA (PRB). ·J Natl Cancer Inst · Pubmed #25713167.

ABSTRACT: BACKGROUND: Bromodomain PHD finger transcription factor (BPTF) plays an important role in chromatin remodeling, but its functional role in tumor progression is incompletely understood. Here we explore the oncogenic effects of BPTF in melanoma. METHODS: The consequences of differential expression of BPTF were explored using shRNA-mediated knockdown in several melanoma cell lines. Immunoblotting was used to assess the expression of various proteins regulated by BPTF. The functional role of BPTF in melanoma progression was investigated using assays of colony formation, invasion, cell cycle, sensitivity to selective BRAF inhibitors, and in xenograft models of melanoma progression (n = 12 mice per group). The biomarker role of BPTF in melanoma progression was assessed using fluorescence in situ hybridization and immunohistochemical analyses. All statistical tests were two-sided. RESULTS: shRNA-mediated BPTF silencing suppressed the proliferative capacity (by 65.5%) and metastatic potential (by 66.4%) of melanoma cells. Elevated BPTF copy number (mean ≥ 3) was observed in 28 of 77 (36.4%) melanomas. BPTF overexpression predicted poor survival in a cohort of 311 melanoma patients (distant metastasis-free survival P = .03, and disease-specific survival P = .008), and promoted resistance to BRAF inhibitors in melanoma cell lines. Metastatic melanoma tumors progressing on BRAF inhibitors contained low BPTF-expressing, apoptotic tumor cell subclones, indicating the continued presence of drug-responsive subclones within tumors demonstrating overall resistance to anti-BRAF agents. CONCLUSIONS: These studies demonstrate multiple protumorigenic functions for BPTF and identify it as a novel target for anticancer therapy. They also suggest the combination of BPTF targeting with BRAF inhibitors as a novel therapeutic strategy for melanomas with mutant BRAF.

24 Article Antitumor activity of miR-1280 in melanoma by regulation of Src. 2015

Sun, Vera / Zhou, Wen B / Nosrati, Mehdi / Majid, Shahana / Thummala, Suresh / de Semir, David / Bezrookove, Vladimir / de Feraudy, Sebastien / Chun, Liane / Schadendorf, Dirk / Debs, Robert / Kashani-Sabet, Mohammed / Dar, Altaf A. ·Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, San Francisco, California, USA. · Department of Urology, Veterans Affairs Medical Center and University of California San Francisco, San Francisco, California, USA. · Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie Universitätsklinikum Essen Hautklinik Huielandstraße, Essen, Germany. ·Mol Ther · Pubmed #25195599.

ABSTRACT: MicroRNAs (miRNAs) play a key role in cancer progression by coordinately repressing target genes involved in cell proliferation, migration, and invasion. miRNAs regulate gene expression by repressing translation or directing sequence-specific degradation of complementary mRNA. Here, we report that expression of miR-1280 is significantly suppressed in human melanoma specimens when compared with nevi, and in human melanoma cell lines when compared with cultured normal human melanocytes. The proto-oncogene Src was identified as a target of miR-1280 action. Levels of Src expression were significantly higher in melanoma samples and cell lines than in nevi and normal melanocytes. miR-1280 overexpression significantly suppressed the luciferase activity of reporter plasmids containing the full-length 3' untranslated region of Src. miR-1280-mediated suppression of Src led to substantial decreases in melanoma cell proliferation, cell cycle progression, invasion, as well as induced melanoma cell apoptosis. The effects of miR-1280 overexpression on melanoma cell proliferation and growth were reversed by Src overexpression. Intratumoral delivery of miR-1280 significantly suppressed melanoma cell growth in vivo. Our results demonstrate a novel role for miR-1280 as a tumor suppressor in melanoma, identify the Src signaling pathway as a target of miR-1280 action, and suggest a potential therapeutic role for miR-1280 in melanoma.

25 Article Immunohistochemical diagnostic and prognostic markers for melanoma. 2014

Nosrati, Mehdi / Kashani-Sabet, Mohammed. ·Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, San Francisco, CA, USA. ·Methods Mol Biol · Pubmed #24258983.

ABSTRACT: Recent studies in our laboratory have identified novel molecular diagnostic and prognostic markers based on analyses in large cohorts of melanoma patients. These markers were initially derived from gene expression profiling analyses of distinct stages of melanoma progression. Immunohistochemical analyses confirmed the differential expression of these markers, and immunohistochemistry-based multimarker assays were developed to assess melanoma diagnosis and prognosis at the molecular level. In this chapter we review the development of these assays and the methodologies used to assess marker expression in both nevi and primary melanomas.

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