Dermatology Commons^™

Cd133-Dependent Activation Of Phosphoinositide 3-Kinase /Akt/Mammalian Target Of Rapamycin Signaling In Melanoma Progression And Drug Resistance, Naji Kharouf, Thomas W. Flanagan, Abdulhadi A. Alamodi, Youssef Al Hmada, Sofie Yasmin Hassan, Hosam Shalaby, Simeon Santourlidis, Sarah Lilly Hassan, Youssef Haikel, Mossad Megahed, Robert T. Brodell, Mohamed Hassan

School of Medicine Faculty Publications

Melanoma frequently harbors genetic alterations in key molecules leading to the aberrant activation of PI3K and its downstream pathways. Although the role of PI3K/AKT/mTOR in melanoma progression and drug resistance is well documented, targeting the PI3K/AKT/mTOR pathway showed less efficiency in clinical trials than might have been expected, since the suppression of the PI3K/mTOR signaling pathway-induced feedback loops is mostly associated with the activation of compensatory pathways such as MAPK/MEK/ERK. Consequently, the development of intrinsic and acquired resistance can occur. As a solid tumor, melanoma is notorious for its heterogeneity. This can be expressed in the form of genetically divergent …

Mechanisms Of Melanoma Progression And Treatment Resistance: Role Of Cancer Stem-Like Cells, Youssef Al Hmada, Robert T. Brodell, Naji Kharouf, Thomas W. Flanagan, Abdulhadi A. Alamodi, Sofie Yasmin Hassan, Hosam Shalaby, Sarah Lilly Hassan, Youssef Haikel, Mosaad Megahed, Simeon Santourlidis, Mohamed Hassan

School of Medicine Faculty Publications

Melanoma is the third most common type of skin cancer, characterized by its heterogeneity and propensity to metastasize to distant organs. Melanoma is a heterogeneous tumor, composed of genetically divergent subpopulations, including a small fraction of melanoma-initiating cancer stem-like cells (CSCs) and many non-cancer stem cells (non-CSCs). CSCs are characterized by their unique surface proteins associated with aberrant signaling pathways with a causal or consequential relationship with tumor progression, drug resistance, and recurrence. Melanomas also harbor significant alterations in functional genes (BRAF, CDKN2A, NRAS, TP53, and NF1). Of these, the most common are the BRAF and NRAS oncogenes, with 50% …

Xtx101, A Tumor-Activated, Fc-Enhanced Anti-Ctla-4 Monoclonal Antibody, Demonstrates Tumor-Growth Inhibition And Tumor-Selective Pharmacodynamics In Mouse Models Of Cancer, Kurt A. Jenkins, Miso Park, Magali Pederzoli-Ribeil, Ugur Eskiocak, Parker Johnson, Wilson Guzman, Megan Mclaughlin, Deborah Moore-Lai, Caitlin O'Toole, Zhen Liu, Benjamin Nicholson, Veronica Flesch, Huawei Qiu, Tim Clackson, Ronan C. O'Hagan, Ulrich Rodeck, Margaret Karow, Jennifer O'Neil, John C. Williams

Department of Dermatology and Cutaneous Biology Faculty Papers

INTRODUCTION: The clinical benefit of the anti-CTLA-4 monoclonal antibody (mAb) ipilimumab has been well established but limited by immune-related adverse events, especially when ipilimumab is used in combination with anti-PD-(L)1 mAb therapy. To overcome these limitations, we have developed XTX101, a tumor-activated, Fc-enhanced anti-CTLA-4 mAb.

METHODS: XTX101 consists of an anti-human CTLA-4 mAb covalently linked to masking peptides that block the complementarity-determining regions, thereby minimizing the mAb binding to CTLA-4. The masking peptides are designed to be released by proteases that are typically dysregulated within the tumor microenvironment (TME), resulting in activation of XTX101 intratumorally. Mutations within the Fc region …

Advances In Melanoma: Epidemiology, Diagnosis, And Prognosis, Shayan Waseh, Jason B. Lee

Department of Dermatology and Cutaneous Biology Faculty Papers

Unraveling the multidimensional complexities of melanoma has required concerted efforts by dedicated community of researchers and clinicians battling against this deadly form of skin cancer. Remarkable advances have been made in the realm of epidemiology, classification, diagnosis, and therapy of melanoma. The treatment of advanced melanomas has entered the golden era as targeted personalized therapies have emerged that have significantly altered the mortality rate. A paradigm shift in the approach to melanoma classification, diagnosis, prognosis, and staging is underway, fueled by discoveries of genetic alterations in melanocytic neoplasms. A morphologic clinicopathologic classification of melanoma is expected to be replaced by …

High Expression Of Talin-1 Is Associated With Tumor Progression And Recurrence In Melanoma Skin Cancer Patients., Yasaman Rezaie, Fahimeh Fattahi, Baharnaz Mashinchi, Kambiz Kamyab Hesari, Sahar Montazeri, Elham Kalantari, Zahra Madjd, Leili Saeednejad Zanjani

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Talin-1 as a component of multi-protein adhesion complexes plays a role in tumor formation and migration in various malignancies. This study investigated Talin-1 in protein levels as a potential prognosis biomarker in skin tumors.

METHODS: Talin-1 was evaluated in 106 skin cancer (33 melanomas and 73 non-melanomas skin cancer (NMSC)) and 11 normal skin formalin-fixed paraffin-embedded (FFPE) tissue samples using immunohistochemical technique on tissue microarrays (TMAs). The association between the expression of Talin-1 and clinicopathological parameters, as well as survival outcomes, were assessed.

RESULTS: Our findings from data minings through bioinformatics tools indicated dysregulation of Talin-1 in mRNA levels …

Inhibitors Of Histone Deacetylase And Mcl-1 Synergistically Reduce Proliferation In Malignant Melanoma, Mehrnoosh Ghafouri, Chester Gauss, Yue Xi Phd, William Azkoul Ii Md, Abby Knudsen, Jordan Zuckerman, Sharon K. Michelhaugh Phd, Sandeep Mittal Md, Andrew M. Fribley Phd

Medical Student Research Symposium

Melanoma is a skin cancer that arises in melanocytes; it is the fifth most common cancer in the United States with approximately 100,000 new cases per year. Current treatments for malignant melanoma are surgical excision, radiation therapy and systemic therapy; however, the five-year survival rate for patients with stage IV is 29.8%. There is an urgent unmet clinical need to investigate novel treatments for these patients. Panobinostat is an orally available histone deacetylase inhibitor used in several hematologic malignancies, but it was ineffective as a single agent against melanoma in Phase 1. To address the insufficiency of options for melanoma …

Racial Differences In Perceived Risk And Sunscreen Usage, Rebecca Fliorent, Alicia Podwojniak, Lianne Adolphe, Katharine Milani

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Background Although White individuals have higher incidence of melanoma, clinical outcomes are worse among patients with skin of color. This disparity arises from delayed diagnoses and treatment that are largely due to clinical and sociodemographic factors. Investigating this discrepancy is crucial to decrease melanoma-related mortality rates in minority communities. A survey was used to investigate the presence of racial disparities in perceived sun exposure risks and behaviors. Methods A survey consisting of 16 questions was deployed via social media to assess skin health knowledge. Over 350 responses were recorded, and the extracted data were analyzed using statistical software. Results Of …

Skin Lesion Segmentation In Dermoscopic Images With Noisy Data, Norsang Lama, Jason Hagerty, Anand Nambisan, Ronald Joe Stanley, William Van Stoecker

Electrical and Computer Engineering Faculty Research & Creative Works

We Propose a Deep Learning Approach to Segment the Skin Lesion in Dermoscopic Images. the Proposed Network Architecture Uses a Pretrained Efficient Net Model in the Encoder and Squeeze-And-Excitation Residual Structures in the Decoder. We Applied This Approach on the Publicly Available International Skin Imaging Collaboration (ISIC) 2017 Challenge Skin Lesion Segmentation Dataset. This Benchmark Dataset Has Been Widely Used in Previous Studies. We Observed Many Inaccurate or Noisy Ground Truth Labels. to Reduce Noisy Data, We Manually Sorted All Ground Truth Labels into Three Categories — Good, Mildly Noisy, and Noisy Labels. Furthermore, We Investigated the Effect of Such …

Pediatric Dermatology Econsult Program With Dermoscopy: Sub Analysis Of Infantile Hemangiomas, Peggy R. Cyr, Madeline Prentiss, Hadjh Ahrns, Abby Markham, Elizabeth V Seiverling

Maine Medical Center

Here we present an analysis of pediatric dermatology eConsults with emphasis on dermoscopy utilization and the impact on eConsult on infantile hemangiomas (IH) management.

Finding The Right Scope: Dermoscopy For Primary Care, Peggy Cyr, Elizabeth Seiverling

Maine Medical Center

Background

• Primary care physicians (PCPs) frequently address skin concerns and perform clinical skin examinations1

• For PCPs, the use of dermoscopy has been shown to increase the sensitivity for skin cancer diagnosis compared to unassisted examinations2,3

• Prior to this study, no formal consensus existed on the fundamental knowledge and skills that PCPs should have with respect to dermoscopy

Objectives

• To develop an expert opinion consensus statement on 2 proficiency standards for PCPs using dermoscopy

Impact Of Dermoscopy Training For Pcps On Nnb To Detect Melanoma, Madeline Prentiss, Kathryn Stevens, Henry Stoddard, Peggy Cyr, Laura Houk, Hadjh Ahrns, Elizabeth Seiverling

Maine Medical Center

The goal of this project was to analyze the impact of dermoscopy training on the number of melanocytic nevi needed to biopsy (NNB) to detect a melanoma in the primary care setting .

Mapping Melanoma Risk And Locating High-Need Regions For Dermoscopy And Skin Biopsy Training, Calla Hladky, Madeline Prentiss, Henry Stoddard, Kathryn Stevens, Elizabeth Seiverling, Peg Cyr

Maine Medical Center

Background- Dermoscopy and skin biopsy trainings have been shown to help improve PCPs’ knowledge of and confidence in detecting skin cancer. The goal of this project was to determine where to focus training efforts in order to maximize our impact and reach regions that face the highest burden of melanoma in the state.

In Vivo T Cell Genetic Engineering With Melanoma-Specific Tcr And Car, Toby Mathew, Vitali Alexeev

Phase 1

Introduction: Adoptive cell transfer (ACT) using T cells genetically engineered to express tumor-specific T cell receptors (TCR) and Chimeric Antigen receptors (CAR) have demonstrated high remission rates in patients with advanced cancers. Targeting of metastatic melanoma with TCR-modified recombinant T cells showed clinically significant response in the majority of patients. However, due to certain drawbacks, this powerful strategy is not yet available for broad clinical application. We propose that in vivo genetic engineering approach may allow overcoming several drawbacks associated ACT and could convert it into generic and cost-effective modality to bring recombinant T cell therapies to general patient …

Immune-Mediated Colitis From Dual Checkpoint Inhibitors., Nishanth Thalambedu, Yasir Khan, Qian Zhang, Shristi Khanal, Ammar Ashfaq

Abington Jefferson Health Papers

Melanoma is a deadly disease with immunotherapy treatment options that emerged in the last few years and have changed the disease outcome. However, it is associated with immune-related toxic effects despite improving survival. We present the case of a 53-year-old woman who had two weeks of diarrhea after she was treated with dual immunotherapy agents for her advanced melanoma. The final workup revealed pancolitis, possibly due to immunotherapy adverse effects. Initial conservative treatment, unfortunately, did not lead to a clinical improvement until a steroid was introduced. We are reporting this case to alert our fellow physicians about the immune-mediated toxicities …

Relating The Gut Metagenome And Metatranscriptome To Immunotherapy Responses In Melanoma Patients., Brandilyn A. Peters, Melissa Wilson, Una Moran, Anna Pavlick, Allison Izsak, Todd Wechter, Jeffrey S. Weber, Iman Osman, Jiyoung Ahn

Department of Medical Oncology Faculty Papers

BACKGROUND: Recent evidence suggests that immunotherapy efficacy in melanoma is modulated by gut microbiota. Few studies have examined this phenomenon in humans, and none have incorporated metatranscriptomics, important for determining expression of metagenomic functions in the microbial community.

METHODS: In melanoma patients undergoing immunotherapy, gut microbiome was characterized in pre-treatment stool using 16S rRNA gene and shotgun metagenome sequencing (n = 27). Transcriptional expression of metagenomic pathways was confirmed with metatranscriptome sequencing in a subset of 17. We examined associations of taxa and metagenomic pathways with progression-free survival (PFS) using 500 × 10-fold cross-validated elastic-net penalized Cox regression.

RESULTS: Higher …

Guidance Of Sentinel Lymph Node Biopsy Decisions In Patients With T1-T2 Melanoma Using Gene Expression Profiling., John T. Vetto, Eddy C. Hsueh, Brian R. Gastman, Larry D. Dillon, Federico A. Monzon, Robert W. Cook, Jennifer Keller, Xin Huang, Andrew Fleming, Preston Hewgley, Pedram Gerami, Sancy Leachman, Jeffrey D. Wayne, Adam C. Berger, Martin D. Fleming

Department of Surgery Faculty Papers

AIM: Can gene expression profiling be used to identify patients with T1-T2 melanoma at low risk for sentinel lymph node (SLN) positivity?

PATIENTS & METHODS: Bioinformatics modeling determined a population in which a 31-gene expression profile test predicted <5% SLN positivity. Multicenter, prospectively-tested (n = 1421) and retrospective (n = 690) cohorts were used for validation and outcomes, respectively.

RESULTS: Patients 55-64 years and ≥65 years with a class 1A (low-risk) profile had SLN positivity rates of 4.9% and 1.6%. Class 2B (high-risk) patients had SLN positivity rates of 30.8% and 11.9%. Melanoma-specific survival was 99.3% for patients ≥55 years with class 1A, T1-T2 tumors and 55.0% for class 2B, SLN-positive, T1-T2 tumors.

CONCLUSION: The 31-gene expression profile test identifies patients …

The Role Of Human Papillomaviruses And Polyomaviruses In Braf-Inhibitor Induced Cutaneous Squamous Cell Carcinoma And Benign Squamoproliferative Lesions, Karin J. Purdie, Charlotte M. Proby, Hasan Rizvi, Heather Griffin, John Doorbar, Mary Sommerlad, Mariet C. Feltkamp, Els Van Der Meijden, Gareth J. Inman, Andrew P. South, Irene M. Leigh, Catherine A. Harwood

Department of Dermatology and Cutaneous Biology Faculty Papers

Background: Human papillomavirus (HPV) has long been proposed as a cofactor in the pathogenesis of cutaneous squamous cell carcinoma (cSCC). More recently, the striking clinico-pathological features of cSCCs that complicate treatment of metastatic melanoma with inhibitors targeting BRAF mutations (BRAFi) has prompted speculation concerning a pathogenic role for oncogenic viruses. Here, we investigate HPV and human polyomaviruses (HPyV) and correlate with clinical, histologic, and genetic features in BRAFi-associated cSCC. Materials and Methods: Patients receiving BRAFi treatment were recruited at Barts Health NHS Trust. HPV DNA was detected in microdissected frozen samples using reverse line probe technology and degenerate and nested …

A Preexisting Rare Pik3ca E545k Subpopulation Confers Clinical Resistance To Mek Plus Cdk4/6 Inhibition In Nras Melanoma And Is Dependent On S6k1 Signaling, Gabriele Romano, Pei-Ling Chen, Ping Song, Jennifer L. Mcquade, Roger J. Liang, Mingguang Liu, Whijae Roh, Dzifa Y. Duose, Fernando C.L. Carapeto, Jun Li, Jessica L.F. Teh, Andrew A. Aplin, Merry Chen, Jianhua Zhang, Alexander J. Lazar, Michael A. Davies, P. Andrew Futreal, Rodabe N. Amaria, David Y. Zhang, Jennifer A. Wargo, Lawrence N. Kwong

Department of Cancer Biology Faculty Papers

Combined MEK and CDK4/6 inhibition (MEKi + CDK4i) has shown promising clinical outcomes in patients with NRAS- mutant melanoma. Here, we interrogated longitudinal biopsies from a patient who initially responded to MEKi + CDK4i therapy but subsequently developed resistance. Whole-exome sequencing and functional validation identified an acquired PIK3CA ^E545K mutation as conferring drug resistance. We demonstrate that PIK3CA ^E545K preexisted in a rare subpopulation that was missed by both clinical and research testing, but was revealed upon multiregion sampling due to PIK3CA ^E545K being nonuniformly distributed. This resistant population rapidly expanded after the initiation of MEKi + CDK4i therapy and …

A Comprehensive Patient-Derived Xenograft Collection Representing The Heterogeneity Of Melanoma., Clemens Krepler, Katrin Sproesser, Patricia Brafford, Marilda Beqiri, Bradley Garman, Min Xiao, Batool Shannan, Andrea Watters, Michela Perego, Gao Zhang, Adina Vultur, Xiangfan Yin, Qin Liu, Ioannis N Anastopoulos, Bradley Wubbenhorst, Melissa A. Wilson, Wei Xu, Giorgos Karakousis, Michael Feldman, Xiaowei Xu, Ravi Amaravadi, Tara C. Gangadhar, David E. Elder, Lauren E. Haydu, Jennifer A. Wargo, Michael A. Davies, Yiling Lu, Gordon B. Mills, Dennie T. Frederick, Michal Barzily-Rokni, Keith T. Flaherty, Dave S. Hoon, Michael Guarino, Joseph J. Bennett, Randall W. Ryan, Nicholas J. Petrelli, Carol L. Shields, Mizue Terai, Takami Sato, Andrew E. Aplin, Alexander Roesch, David Darr, Steve Angus, Rakesh Kumar, Ensar Halilovic, Giordano Caponigro, Sebastien Jeay, Jens Wuerthner, Annette Walter, Matthias Ocker, Matthew B. Boxer, Lynn Schuchter, Katherine L Nathanson, Meenhard Herlyn

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

Therapy of advanced melanoma is changing dramatically. Following mutational and biological subclassification of this heterogeneous cancer, several targeted and immune therapies were approved and increased survival significantly. To facilitate further advancements through pre-clinical in vivo modeling, we have established 459 patient-derived xenografts (PDX) and live tissue samples from 384 patients representing the full spectrum of clinical, therapeutic, mutational, and biological heterogeneity of melanoma. PDX have been characterized using targeted sequencing and protein arrays and are clinically annotated. This exhaustive live tissue resource includes PDX from 57 samples resistant to targeted therapy, 61 samples from responders and non-responders to immune checkpoint …

The Prognostic Importance Of Scalp Location In Primary Head And Neck Melanoma., Junko Ozao-Choy, Daniel W Nelson, Jason Hiles, Stacey L Stern, Jeong Lim Yoon, Myung Shin Sim, Mark Faries

Articles, Abstracts, and Reports

BACKGROUND AND OBJECTIVES: For patients with cutaneous melanoma, primary tumors located in the head and neck is associated with poor outcomes. The reason for this difference and whether it is applicable to all locations within the head and neck remains unclear. We hypothesized that scalp melanoma is uniquely distinguished from other anatomic sites and is independently responsible for the poor prognosis of head and neck melanoma.

METHODS: Query and analysis of a prospectively maintained melanoma database of all patients treated for primary cutaneous melanoma from 1971 to 2010.

RESULTS: Of 11 384 patients identified, 7% (n = 799) of lesions …

Impact Of Time Between Diagnosis And Slnb On Outcomes In Cutaneous Melanoma., Daniel W Nelson, Stacey Stern, David E Elashoff, Robert Elashoff, John F Thompson, Nicola Mozzillo, Omgo E Nieweg, Harald J Hoekstra, Alistair J Cochran, Mark B Faries

Articles, Abstracts, and Reports

BACKGROUND: Hypothetically, delay between melanoma diagnosis and SLNB could affect outcomes, either adversely by allowing growth and dissemination of metastases, or beneficially by allowing development of an anti-melanoma immune response. Available data are conflicting about the effect of SLNB delay on patient survival. Our objective was to determine whether delay between initial diagnosis and SLNB affects outcomes in patients with cutaneous melanoma.

STUDY DESIGN: We performed query and analysis of a large prospectively maintained database of patients with primary cutaneous melanomas undergoing SLNB. An independent dataset from MSLT-1 (Multicenter Selective Lymphadenectomy Trial-1) was used for validation. Primary outcomes included disease-free …

New Approaches To Melanoma Prevention, June K. Robinson, Katie Baker, Joel J. Hillhouse

ETSU Faculty Works

Skin cancer is a major public health concern, and tanning remains a modifiable risk factor. Multidimensional influences, including psychosocial, individual, environmental, and policy-related factors, create the milieu for individuals to engage in tanning. Parents and physicians can modify the behavior of teens and young adults using strategies based on harm reduction. Environmental and policy-related factors similar to those used to limit smoking by restricting access of minors to cigarettes in the United States in the 20th century need to be created. Federal regulations can restrict direct advertising and the excise tax can be increased to a prohibitive amount. Social networking …

Is Pregnancy-Associated Melanoma Associated With Adverse Outcomes?, Maris S Jones, Jihey Lee, Stacey L Stern, Mark Faries

Articles, Abstracts, and Reports

BACKGROUND: Melanoma is the most common malignancy encountered during pregnancy. Conflicting data have led to ongoing confusion regarding pregnancy-associated melanoma (PAM) in the media and among the public. The objective of this study was to better characterize both the clinical presentation of PAM and its prognostic implications.

STUDY DESIGN: Female patients of reproductive age, with stage 0 to IV cutaneous melanoma, were identified from our prospectively maintained database. Clinical and histopathologic factors were analyzed with appropriate statistical methods. Univariable and then multivariable analysis were used on matched data to compare disease-free survival (DFS), overall survival (OS), and melanoma-specific survival (MSS) …

Pathologists' Diagnosis Of Invasive Melanoma And Melanocytic Proliferations: Observer Accuracy And Reproducibility Study., Joann G Elmore, Raymond L Barnhill, David E Elder, Gary M Longton, Margaret S Pepe, Lisa M Reisch, Patricia A Carney, Linda J Titus, Heidi D Nelson, Tracy Onega, Anna N A Tosteson, Martin A Weinstock, Stevan R Knezevich, Michael W Piepkorn

Articles, Abstracts, and Reports

No abstract provided.

Inhibition Of Age-Related Therapy Resistance In Melanoma By Rosiglitazone-Mediated Induction Of Klotho., Reeti Behera, Amanpreet Kaur, Marie R. Webster, Suyeon Kim, Abibatou Ndoye, Curtis H. Kugel, Gretchen M. Alicea, Joshua Wang, Kanad Ghosh, Phil Cheng, Sofia Lisanti, Katie Marchbank, Vanessa Dang, Mitchell Levesque, Reinhard Dummer, Xiaowei Xu, Meenhard Herlyn, Andrew E. Aplin, Alexander Roesch, Cecilia Caino, Dario C. Altieri, Ashani T. Weeraratna

Department of Cancer Biology Faculty Papers

Purpose: Aging is a poor prognostic factor for melanoma. We have shown that melanoma cells in an aged microenvironment are more resistant to targeted therapy than identical cells in a young microenvironment. This is dependent on age-related secreted factors. Klotho is an age-related protein whose serum levels decrease dramatically by age 40. Most studies on klotho in cancer have focused on the expression of klotho in the tumor cell. We have shown that exogenous klotho inhibits internalization and signaling of Wnt5A, which drives melanoma metastasis and resistance to targeted therapy. We investigate here whether increasing klotho in the aged microenvironment …

Completion Dissection Or Observation For Sentinel-Node Metastasis In Melanoma., Mark Faries, John F Thompson, Alistair J Cochran, Robert H Andtbacka, Nicola Mozzillo, Jonathan S Zager, Tiina Jahkola, Tawnya L Bowles, Alessandro Testori, Peter D Beitsch, Harald J Hoekstra, Marc Moncrieff, Christian Ingvar, Michel W J M Wouters, Michael S Sabel, Edward A Levine, Doreen Agnese, Michael Henderson, Reinhard Dummer, Carlo R Rossi, Rogerio I Neves, Steven D Trocha, Frances Wright, David R Byrd, Maurice Matter, Eddy Hsueh, Alastair Mackenzie-Ross, Douglas B Johnson, Patrick Terheyden, Adam C Berger, Tara L Huston, Jeffrey D Wayne, B Mark Smithers, Heather B Neuman, Schlomo Schneebaum, Jeffrey E Gershenwald, Charlotte E Ariyan, Darius C Desai, Lisa Jacobs, Kelly M Mcmasters, Anja Gesierich, Peter Hersey, Steven D Bines, John M Kane, Richard J Barth, Gregory Mckinnon, Jeffrey M Farma, Erwin Schultz, Sergi Vidal-Sicart, Richard A Hoefer, James M Lewis, Randall Scheri, Mark C Kelley, Omgo E Nieweg, R Dirk Noyes, Dave S B Hoon, He-Jing Wang, David A Elashoff, Robert M Elashoff

Articles, Abstracts, and Reports

BACKGROUND: Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear.

METHODS: In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis.

RESULTS: Immediate completion …

Thin Melanoma With Nodal Involvement: Analysis Of Demographic, Pathologic, And Treatment Factors With Regard To Prognosis., Giorgos Karakousis, Phyllis A Gimotty, Edmund K Bartlett, Myung-Shin Sim, Madalyn G Neuwirth, Douglas Fraker, Brian J Czerniecki, Mark B Faries

Articles, Abstracts, and Reports

BACKGROUND: Although only a small proportion of thin melanomas result in lymph node metastasis, the abundance of these lesions results in a relatively large absolute number of patients with a diagnosis of nodal metastases, determined by either sentinel lymph node (SLN) biopsy or clinical nodal recurrence (CNR).

METHODS: Independent cohorts with thin melanoma and either SLN metastasis or CNR were identified at two melanoma referral centers. At both centers, SLN metastasis patients were included. At center 1, the CNR cohort included patients with initial negative clinical nodal evaluation followed by CNR. At center 2, the CNR cohort was restricted to …

Atr Mutations Promote The Growth Of Melanoma Tumors By Modulating The Immune Microenvironment., Chi-Fen Chen, Rolando Ruiz-Vega, Priya Vasudeva, Francisco Espitia, Tatiana B Krasieva, Sebastien De Feraudy, Bruce J Tromberg, Sharon Huang, Chad P Garner, Jie Wu, Dave S B Hoon, Anand K Ganesan

Articles, Abstracts, and Reports

Melanomas accumulate a high burden of mutations that could potentially generate neoantigens, yet somehow suppress the immune response to facilitate continued growth. In this study, we identify a subset of human melanomas that have loss-of-function mutations in ATR, a kinase that recognizes and repairs UV-induced DNA damage and is required for cellular proliferation. ATR mutant tumors exhibit both the accumulation of multiple mutations and the altered expression of inflammatory genes, resulting in decreased T cell recruitment and increased recruitment of macrophages known to spur tumor invasion. Taken together, these studies identify a mechanism by which melanoma cells modulate the immune …

Challenges To Smartphone Applications For Melanoma Detection, Jordan V. Wang, Lance W. Chapman, Matthew S. Keller

Department of Dermatology and Cutaneous Biology Faculty Papers

This commentary addresses the emerging market for health-related smartphone applications. Specific to dermatology, there has been a significant increase not only in applications that promote skin cancer awareness and education but also in those meant for detection. With evidence showing that 365 dermatology-related applications were available in 2014--up from 230 in 2012--and that 1 in 5 patients under the age of 50 have used a smartphone to help diagnose a skin problem, there is clearly a large subset of patients participating in this growing trend. Therefore, we are obligated to take a closer look into this phenomenon. Studies have shown …

The Influence Of Tumor Regression, Solar Elastosis, And Patient Age On Pathologists' Interpretation Of Melanocytic Skin Lesions., Linda Titus, Raymond L Barnhill, Jason P Lott, Michael W Piepkorn, David E Elder, Paul D Frederick, Heidi D Nelson, Patricia A Carney, Stevan R Knezevich, Martin A Weinstock, Joann G Elmore

Articles, Abstracts, and Reports

It is not known whether patient age or tumor characteristics such as tumor regression or solar elastosis influence pathologists' interpretation of melanocytic skin lesions (MSLs). We undertook a study to determine the influence of these factors, and to explore pathologist's characteristics associated with the direction of diagnosis. To meet our objective, we designed a cross-sectional survey study of pathologists' clinical practices and perceptions. Pathologists were recruited from diverse practices in 10 states in the United States. We enrolled 207 pathologist participants whose practice included the interpretation of MSLs. Our findings indicated that the majority of pathologists (54.6%) were influenced toward …