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https://www.readbyqxmd.com/read/27427400/neuropeptide-y-expression-in-primary-cutaneous-melanoma
#1
B Pérez Tato, Á Juarranz, L Nájera, M C Mihm, P Fernández, Y Gilaberte, S González
BACKGROUND: Neuropeptide Y (NPY) is involved in the carcinogenesis of different tumours, especially neural crest-derived tumours. OBJECTIVE: The aim of our study is to investigate the expression of NPY on melanoma and its relation with prognostic histological parameters and survival. METHODS: This is a retrospective observational study of two independent series, with a total of 79 primary melanomas, diagnosed in two independent University Hospitals in Spain, from January 2000 to December 2004...
July 18, 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/27189823/evaluation-of-the-melanocytic-pathology-assessment-tool-and-hierarchy-for-diagnosis-mpath-dx-classification-scheme-for-diagnosis-of-cutaneous-melanocytic-neoplasms-results-from-the-international-melanoma-pathology-study-group
#2
Jason P Lott, Joann G Elmore, Ge A Zhao, Stevan R Knezevich, Paul D Frederick, Lisa M Reisch, Emily Y Chu, Martin G Cook, Lyn M Duncan, Rosalie Elenitsas, Pedram Gerami, Gilles Landman, Lori Lowe, Jane L Messina, Martin C Mihm, Joost J van den Oord, Michael S Rabkin, Birgitta Schmidt, Christopher R Shea, Sook Jung Yun, George X Xu, Michael W Piepkorn, David E Elder, Raymond L Barnhill
BACKGROUND: Pathologists use diverse terminology when interpreting melanocytic neoplasms, potentially compromising quality of care. OBJECTIVE: We sought to evaluate the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) scheme, a 5-category classification system for melanocytic lesions. METHODS: Participants (n = 16) of the 2013 International Melanoma Pathology Study Group Workshop provided independent case-level diagnoses and treatment suggestions for 48 melanocytic lesions...
August 2016: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/27020390/tumour-infiltrating-lymphocytes-in-melanoma-prognosis-and%C3%A2-cancer%C3%A2-immunotherapy
#3
Nayoung Lee, Labib R Zakka, Martin C Mihm, Tobias Schatton
The field of systemic cancer therapy for metastatic disease has entered an exciting era with the advent of novel immunomodulatory strategies targeting immune checkpoints. At the heart of these promising efforts are the tumour-infiltrating lymphocytes (TILs). As the reports demonstrating efficacy of modulating TIL effector function in patients with advanced stage cancer continue to accrue, it has become essential to better understand TIL immunobiology in order to further improve clinical outcome. In addition to providing an overview of the current immunotherapies available for metastatic melanoma, this review will briefly introduce the history and classification of TILs...
February 2016: Pathology
https://www.readbyqxmd.com/read/27020384/genomic-aberrations-in-spitzoid-melanocytic-tumours-and-their-implications-for-diagnosis-prognosis-and-therapy
#4
Thomas Wiesner, Heinz Kutzner, Lorenzo Cerroni, Martin C Mihm, Klaus J Busam, Rajmohan Murali
Histopathological evaluation of melanocytic tumours usually allows reliable distinction of benign melanocytic naevi from melanoma. More difficult is the histopathological classification of Spitz tumours, a heterogeneous group of tumours composed of large epithelioid or spindle-shaped melanocytes. Spitz tumours are biologically distinct from conventional melanocytic naevi and melanoma, as exemplified by their distinct patterns of genetic aberrations. Whereas common acquired naevi and melanoma often harbour BRAF mutations, NRAS mutations, or inactivation of NF1, Spitz tumours show HRAS mutations, inactivation of BAP1 (often combined with BRAF mutations), or genomic rearrangements involving the kinases ALK, ROS1, NTRK1, BRAF, RET, and MET...
February 2016: Pathology
https://www.readbyqxmd.com/read/27020382/advances-in-melanoma-revolutionary-progress-delivering-improved-patient-management-and-outcomes
#5
EDITORIAL
Richard A Scolyer, Ricardo E Vilain, Martin C Mihm
No abstract text is available yet for this article.
February 2016: Pathology
https://www.readbyqxmd.com/read/26974966/decreased-tumor-infiltrating-lymphocytes-in-nodular-melanomas-compared-with-matched-superficial-spreading-melanomas
#6
Richard L Lin, Thomas J Wang, Cara J Joyce, Martin C Mihm, George F Murphy, Christine G Lian, Jennifer Y Lin
Melanoma causes over 9000 deaths annually in the USA. Among its subtypes, nodular melanoma leads to a disproportionate number of fatalities compared with superficial spreading melanoma, the most common subtype. Recent breakthroughs in melanoma research have indicated a strong connection between melanoma virulence and the immune system. We hypothesize that the aggression of nodular melanoma may, in part, be because of decreased recognition by the immune system, as represented by a decreased presence of tumor-infiltrating lymphocytes (TILs), compared with its superficial spreading counterpart...
October 2016: Melanoma Research
https://www.readbyqxmd.com/read/26619946/future-perspectives-in-melanoma-research-meeting-report-from-the-melanoma-bridge-napoli-december-3rd-6th-2014
#7
Paolo A Ascierto, Michael Atkins, Carlo Bifulco, Gerardo Botti, Alistair Cochran, Michael Davies, Sandra Demaria, Reinhard Dummer, Soldano Ferrone, Silvia Formenti, Thomas F Gajewski, Claus Garbe, Samir Khleif, Rolf Kiessling, Roger Lo, Paul Lorigan, Grant Mc Arthur, Giuseppe Masucci, Ignacio Melero, Martin Mihm, Giuseppe Palmieri, Giorgio Parmiani, Igor Puzanov, Pedro Romero, Bastian Schilling, Barbara Seliger, David Stroncek, Janis Taube, Sara Tomei, Hassane M Zarour, Alessandro Testori, Ena Wang, Jérôme Galon, Gennaro Ciliberto, Nicola Mozzillo, Francesco M Marincola, Magdalena Thurin
The fourth "Melanoma Bridge Meeting" took place in Naples, December 3-6th, 2014. The four topics discussed at this meeting were: Molecular and Immunological Advances, Combination Therapies, News in Immunotherapy, and Tumor Microenvironment and Biomarkers. Until recently systemic therapy for metastatic melanoma patients was ineffective, but recent advances in tumor biology and immunology have led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS)...
November 30, 2015: Journal of Translational Medicine
https://www.readbyqxmd.com/read/26462027/loss-of-the-epigenetic-mark-5-hydroxymethylcytosine-correlates-with-small-cell-nevoid-subpopulations-and-assists-in-microstaging-of-human-melanoma
#8
Jonathan J Lee, Martin Cook, Martin C Mihm, Shuyun Xu, Qian Zhan, Thomas J Wang, George F Murphy, Christine G Lian
Melanomas in the vertical growth phase (VGP) not infrequently demonstrate cellular heterogeneity. One commonly encountered subpopulation displays small cell/nevoid morphology. Although its significance remains unknown, such subpopulations may pose diagnostic issues when faced with differentiating such changes from associated nevus or mistaking such regions for nevic maturation (pseudomaturation). That 'loss' of the epigenetic biomarker, 5-hydroxymethylcytosine (5-hmC), is a hallmark for melanoma and correlates with virulence prompted us to explore the diagnostic utility and biological implications of 5-hmC immunohistochemistry (IHC) in melanomas with small cell/nevoid subpopulations...
November 10, 2015: Oncotarget
https://www.readbyqxmd.com/read/26359984/melanoma-cell-intrinsic-pd-1-receptor-functions-promote-tumor-growth
#9
Sonja Kleffel, Christian Posch, Steven R Barthel, Hansgeorg Mueller, Christoph Schlapbach, Emmanuella Guenova, Christopher P Elco, Nayoung Lee, Vikram R Juneja, Qian Zhan, Christine G Lian, Rahel Thomi, Wolfram Hoetzenecker, Antonio Cozzio, Reinhard Dummer, Martin C Mihm, Keith T Flaherty, Markus H Frank, George F Murphy, Arlene H Sharpe, Thomas S Kupper, Tobias Schatton
Therapeutic antibodies targeting programmed cell death 1 (PD-1) activate tumor-specific immunity and have shown remarkable efficacy in the treatment of melanoma. Yet, little is known about tumor cell-intrinsic PD-1 pathway effects. Here, we show that murine and human melanomas contain PD-1-expressing cancer subpopulations and demonstrate that melanoma cell-intrinsic PD-1 promotes tumorigenesis, even in mice lacking adaptive immunity. PD-1 inhibition on melanoma cells by RNAi, blocking antibodies, or mutagenesis of melanoma-PD-1 signaling motifs suppresses tumor growth in immunocompetent, immunocompromised, and PD-1-deficient tumor graft recipient mice...
September 10, 2015: Cell
https://www.readbyqxmd.com/read/26242760/reflections-on-the-histopathology-of-tumor-infiltrating-lymphocytes-in-melanoma-and-the-host-immune-response
#10
REVIEW
Martin C Mihm, James J Mulé
In the past five decades, the role for lymphocytes in host immune response to tumors has been shown, at least in some patients, to be a critical component in disease prognosis. Also, the heterogeneity of lymphocytes has been documented, including the existence of regulatory T cells that suppress the immune response. As the functions of lymphocytes have become better defined in terms of antitumor immunity, specific targets on lymphocytes have been uncovered. The appreciation of the role of immune checkpoints has also led to therapeutic approaches that illustrate the effectiveness of blocking negative regulators of the antitumor immune response...
August 2015: Cancer Immunology Research
https://www.readbyqxmd.com/read/26221190/targeted-next-generation-sequencing-reveals-high-frequency-of-mutations-in-epigenetic-regulators-across-treatment-na%C3%A3-ve-patient-melanomas
#11
Jonathan J Lee, Lynette M Sholl, Neal I Lindeman, Scott R Granter, Alvaro C Laga, Priyanka Shivdasani, Gary Chin, Jason J Luke, Patrick A Ott, F Stephen Hodi, Martin C Mihm, Jennifer Y Lin, Andrew E Werchniak, Harley A Haynes, Nancy Bailey, Robert Liu, George F Murphy, Christine G Lian
BACKGROUND: Recent developments in genomic sequencing have advanced our understanding of the mutations underlying human malignancy. Melanoma is a prototype of an aggressive, genetically heterogeneous cancer notorious for its biologic plasticity and predilection towards developing resistance to targeted therapies. Evidence is rapidly accumulating that dysregulated epigenetic mechanisms (DNA methylation/demethylation, histone modification, non-coding RNAs) may play a central role in the pathogenesis of melanoma...
2015: Clinical Epigenetics
https://www.readbyqxmd.com/read/25805798/biologic-activity-of-autologous-granulocyte-macrophage-colony-stimulating-factor-secreting-alveolar-soft-part-sarcoma-and-clear-cell-sarcoma-vaccines
#12
John M Goldberg, David E Fisher, George D Demetri, Donna Neuberg, Stephen A Allsop, Catia Fonseca, Yukoh Nakazaki, David Nemer, Chandrajit P Raut, Suzanne George, Jeffrey A Morgan, Andrew J Wagner, Gordon J Freeman, Jerome Ritz, Cecilia Lezcano, Martin Mihm, Christine Canning, F Stephen Hodi, Glenn Dranoff
PURPOSE: Alveolar soft-part sarcoma (ASPS) and clear cell sarcoma (CCS) are rare mesenchymal malignancies driven by chromosomal translocations that activate members of the microphthalmia transcription factor (MITF) family. However, in contrast to malignant melanoma, little is known about their immunogenicity. To learn more about the host response to ASPS and CCS, we conducted a phase I clinical trial of vaccination with irradiated, autologous sarcoma cells engineered by adenoviral-mediated gene transfer to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF)...
July 15, 2015: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/25756799/melanoma-cell-galectin-1-ligands-functionally-correlate-with-malignant-potential
#13
Erika M Yazawa, Jenna E Geddes-Sweeney, Filiberto Cedeno-Laurent, Kempland C Walley, Steven R Barthel, Matthew J Opperman, Jennifer Liang, Jennifer Y Lin, Tobias Schatton, Alvaro C Laga, Martin C Mihm, Abrar A Qureshi, Hans R Widlund, George F Murphy, Charles J Dimitroff
Galectin-1 (Gal-1)-binding to Gal-1 ligands on immune and endothelial cells can influence melanoma development through dampening antitumor immune responses and promoting angiogenesis. However, whether Gal-1 ligands are functionally expressed on melanoma cells to help control intrinsic malignant features remains poorly understood. Here, we analyzed expression, identity, and function of Gal-1 ligands in melanoma progression. Immunofluorescent analysis of benign and malignant human melanocytic neoplasms revealed that Gal-1 ligands were abundant in severely dysplastic nevi, as well as in primary and metastatic melanomas...
July 2015: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/25479927/bap1-and-brafv600e-expression-in-benign-and-malignant-melanocytic-proliferations
#14
Adriano Piris, Martin C Mihm, Mai P Hoang
BAP1 (BRCA1-associated protein 1) is a tumor suppressor gene whose mutations have recently been reported to increase susceptibility for the development of uveal melanoma, cutaneous atypical and epithelioid melanocytic lesions, clear cell renal cell carcinoma, and other tumors. Screening for BAP1 mutation/loss/inactivation and BRAFV600E mutation can be done by immunohistochemistry. We investigated BAP1 and BRAFV600E expression in 193 sporadic melanocytic lesions (11 dermal nevi, 20 congenital nevi, 40 primary and nondesmoplastic melanomas, 40 desmoplastic melanomas, 23 metastatic melanomas, 17 Spitz nevi, 19 atypical Spitz nevi, 8 atypical Spitz tumors, 14 proliferative nodules arising in congenital nevi, 1 nevus during pregnancy) and 30 melanocytic lesions from 3 patients with family history of uveal melanoma and BAP1 germline mutation...
February 2015: Human Pathology
https://www.readbyqxmd.com/read/25300464/the-plexiform-spindle-cell-nevus-nevi-and-atypical-variants-report-of-128-cases
#15
Tawny Hung, Aparche Yang, Martin C Mihm, Raymond L Barnhill
The plexiform spindle cell nevus (PLXSCN) is a distinct melanocytic lesion that often provokes concern for melanoma. We describe the features of 119 typical PLXSCNs and 9 atypical/high-grade lesions. Histologically, all cases had a fascicular plexiform architecture and were composed of predominately spindled cells. The 6 atypical plexiform spindle cell tumors (PLXSCTs) exhibited features such as greater mitotic activity, increased cellularity/nodular confluence, and more concerning cytological atypia. Three high-grade tumors (perhaps evolving plexiform spindle cell melanomas) had additional alarming clinical or histologic characteristics, such as patient age greater than 40 years, greater degree of cellularity, higher degree of cytological atypia, mitotic rate greater than 3/mm(2), regional lymph node metastases, and greater than 1 positive sentinel lymph node...
December 2014: Human Pathology
https://www.readbyqxmd.com/read/25118781/deep-penetrating-nevus-like-borderline-tumors-a-unique-subset-of-ambiguous-melanocytic-tumors-with-malignant-potential-and-normal-cytogenetics
#16
Cynthia M Magro, Ronnie M Abraham, Ruifeng Guo, Shibo Li, Xuan Wang, Steven Proper, A Neil Crowson, Martin Mihm
BACKGROUND: Deep penetrating nevi (DPN) are a relatively uncommon subtype of melanocytic nevi. A small subset of these lesions exhibit atypical features (cytologic and architectural atypia, mitotic activity) seen in melanoma. These lesions we term the deep penetrating nevus-like borderline tumor. Unequivocal melanomas can show overlapping morphologic features of DPN, which have been termed plexiform melanomas. PATIENTS AND METHODS: 40 cases of DPN-like borderline tumor were identified along with 6 cases of plexiform melanoma...
September 2014: European Journal of Dermatology: EJD
https://www.readbyqxmd.com/read/24838938/bevacizumab-plus-ipilimumab-in-patients-with-metastatic-melanoma
#17
F Stephen Hodi, Donald Lawrence, Cecilia Lezcano, Xinqi Wu, Jun Zhou, Tetsuro Sasada, Wanyong Zeng, Anita Giobbie-Hurder, Michael B Atkins, Nageatte Ibrahim, Philip Friedlander, Keith T Flaherty, George F Murphy, Scott Rodig, Elsa F Velazquez, Martin C Mihm, Sara Russell, Pamela J DiPiro, Jeffrey T Yap, Nikhil Ramaiya, Annick D Van den Abbeele, Maria Gargano, David McDermott
Ipilimumab improves survival in advanced melanoma and can induce immune-mediated tumor vasculopathy. Besides promoting angiogenesis, vascular endothelial growth factor (VEGF) suppresses dendritic cell maturation and modulates lymphocyte endothelial trafficking. This study investigated the combination of CTLA4 blockade with ipilimumab and VEGF inhibition with bevacizumab. Patients with metastatic melanoma were treated in four dosing cohorts of ipilimumab (3 or 10 mg/kg) with four doses at 3-week intervals and then every 12 weeks, and bevacizumab (7...
July 2014: Cancer Immunology Research
https://www.readbyqxmd.com/read/24618612/histomorphologic-assessment-and-interobserver-diagnostic-reproducibility-of-atypical-spitzoid-melanocytic-neoplasms-with-long-term-follow-up
#18
MULTICENTER STUDY
Pedram Gerami, Klaus Busam, Alistair Cochran, Martin G Cook, Lyn M Duncan, David E Elder, Douglas R Fullen, Joan Guitart, Philip E LeBoit, Martin C Mihm, Victor G Prieto, Michael S Rabkin, Richard A Scolyer, Xiaowei Xu, Sook Jung Yun, Roxana Obregon, Pedram Yazdan, Chelsea Cooper, Bing Bing Weitner, Alfred Rademaker, Raymond L Barnhill
Predicting clinical behavior of atypical Spitz tumors remains problematic. In this study, we assessed interobserver agreement of diagnosis by 13 expert dermatopathologists for atypical Spitz tumors (n=75). We determined which histomorphologic features were most heavily weighted for their diagnostic significance by the experts and also which histomorphologic features had a statistically significant correlation with clinical outcome. There was a low interobserver agreement among the experts in categorizing lesions as malignant versus nonmalignant (κ=0...
July 2014: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/24531700/age-as-a-predictor-of-sentinel-node-metastasis-among-patients-with-localized-melanoma-an-inverse-correlation-of-melanoma-mortality-and-incidence-of-sentinel-node-metastasis-among-young-and-old-patients
#19
COMPARATIVE STUDY
Charles M Balch, John F Thompson, Jeffrey E Gershenwald, Seng-Jaw Soong, Shouluan Ding, Kelly M McMasters, Daniel G Coit, Alexander M M Eggermont, Phyllis A Gimotty, Timothy M Johnson, John M Kirkwood, Stanley P Leong, Merrick I Ross, David R Byrd, Alistair J Cochran, Martin C Mihm, Donald L Morton, Michael B Atkins, Keith T Flaherty, Vernon K Sondak
PURPOSE: We have previously reported that older patients with clinical stage I and II primary cutaneous. Melanoma had lower survival rates compared to younger patients. We postulated that the incidence of nodal metastasis would therefore be higher among older melanoma patients. METHODS: The expanded American Joint Committee on Cancer melanoma staging database contains a cohort of 7,756 melanoma patients who presented without clinical evidence of regional lymph node or distant metastasis and who underwent a sentinel node biopsy procedure as a component of their staging assessment...
April 2014: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/24434899/evaluation-of-stromal-hgf-immunoreactivity-as-a-biomarker-for-melanoma-response-to-raf-inhibitors
#20
Cecilia Lezcano, Chung-Wei Lee, Allison R Larson, Alexander M Menzies, Richard F Kefford, John F Thompson, Martin C Mihm, Shuji Ogino, Georgina V Long, Richard A Scolyer, George F Murphy
Of more than 150 000 published studies evaluating new biomarkers, fewer than 100 biomarkers have been implemented for patient care. One reason for this is lack of rigorous testing by the medical community to validate claims for biomarker clinical relevance, and potential reluctance to publish negative results when confirmation is not obtained. Here we sought to determine the utility and reproducibility of immunohistochemical detection of hepatocyte growth factor (HGF) in melanoma tissue, an approach of potential assistance in defining patients with innate resistance to BRAF inhibitor therapy...
September 2014: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
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