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Molecular diagnostic melanoma

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https://www.readbyqxmd.com/read/27899957/next-generation-sequencing-in-nsclc-and-melanoma-patients-a-cost-and-budget-impact-analysis
#1
Rosa A van Amerongen, Valesca P Retèl, Veerle Mh Coupé, Petra M Nederlof, Maartje J Vogel, Wim H van Harten
Next-generation sequencing (NGS) has reached the molecular diagnostic laboratories. Although the NGS technology aims to improve the effectiveness of therapies by selecting the most promising therapy, concerns are that NGS testing is expensive and that the 'benefits' are not yet in relation to these costs. In this study, we give an estimation of the costs and an institutional and national budget impact of various types of NGS tests in non-small-cell lung cancer (NSCLC) and melanoma patients within The Netherlands...
2016: Ecancermedicalscience
https://www.readbyqxmd.com/read/27890785/genomic-characterization-of-dysplastic-nevi-unveils-implications-for-diagnosis-of-melanoma
#2
Rachel D Melamed, Iraz T Aydin, Geena Susan Rajan, Robert Phelps, David N Silvers, Kevin J Emmett, Georg Brunner, Raul Rabadan, Julide Tok Celebi
A well-defined risk factor and precursor for cutaneous melanoma is the dysplastic nevus. These benign tumors represent clonal hyperproliferation of melanocytes that are in a senescent-like state, but with occasional malignant transformation events. To portray the mutational repertoire of dysplastic nevi in patients with the dysplastic nevus syndrome, and to determine the discriminatory profiles of melanocytic nevi (including dysplastic nevi) from melanoma, we sequenced exomes of melanocytic nevi including dysplastic nevi (n = 19), followed by a targeted gene panel (785 genes) characterization of melanocytic nevi (n = 46) and primary melanomas (n = 42)...
November 24, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27889782/molecular-pathology-a-requirement-for-precision-medicine-in-cancer
#3
Manfred Dietel
The increasing importance of targeting drugs and check-point inhibitors in the treatment of several tumor entities (breast, colon, lung, malignant melanoma, lymphoma, etc.) and the necessity of a companion diagnostic (HER2, (pan)RAS, EGFR, ALK, BRAF, ROS1, MET, PD-L1, etc.) is leading to new challenges for surgical pathology. Since almost all the biomarkers to be specifically detected are tissue based, a precise and reliable diagnostic is absolutely crucial. To meet this challenge surgical pathology has adapted a number of molecular methods (semi-quantitative immunohistochemistry, fluorescence in situ hybridization, PCR and its multiple variants, (pyro/Sanger) sequencing, next generation sequencing (amplicon, whole exome, whole genome), DNA arrays, methylation analyses, etc...
2016: Oncology Research and Treatment
https://www.readbyqxmd.com/read/27878432/histopathologic-diagnosis-of-brain-metastases-current-trends-in-management-and-future-considerations
#4
Lien Bekaert, Evelyne Emery, Guénaëlle Levallet, Emmanuèle Lechapt-Zalcman
Confronted with brain metastases (BM), pathologists aim to rule out a primary central nervous system (CNS) tumor and to identify or verify the primary tumor site to guide the clinician to specific therapies. Apart from morphological features, ancillary immunohistochemical analysis is the most effective tool for characterizing a metastatic neoplasm of unknown origin. A limited array of antibodies is used, taking into account relevant clinical information and the known brain tropism of lung cancer, breast cancer and melanoma...
November 22, 2016: Brain Tumor Pathology
https://www.readbyqxmd.com/read/27874206/spitz-nevi-and-other-spitzoid-neoplasms-in-children-overview-of-incidence-data-and-diagnostic-criteria
#5
REVIEW
Emi Dika, Giulia Maria Ravaioli, Pier Alessandro Fanti, Iria Neri, Annalisa Patrizi
Spitz nevi are benign melanocytic neoplasms characterized by epithelioid or spindle melanocytes or both. In some rare cases their presentation overlaps with the clinical and histopathologic features of malignant melanoma, so a differential diagnosis can be difficult to make. Intermediate forms between Spitz nevi and malignant melanoma, with unpredictable behavior, have been called atypical Spitz tumors. A literature search was performed to review the clinical, dermoscopic, genetic, and histopathologic aspects of spitzoid tumors...
November 22, 2016: Pediatric Dermatology
https://www.readbyqxmd.com/read/27863476/is-immunohistochemistry-of-braf-v600e-useful-as-a-screening-tool-and-during-progression-disease-of-melanoma-patients
#6
Laura Schirosi, Sabino Strippoli, Francesca Gaudio, Giusi Graziano, Ondina Popescu, Michele Guida, Giovanni Simone, Anita Mangia
BACKGROUND: In clinical practice the gold standard method to assess BRAF status in patients with metastatic melanoma is based on molecular assays. Recently, a mutation-specific monoclonal antibody (VE1), which detects the BRAF V600E mutated protein, has been developed. With this study we aimed to confirm the clinical value of the VE1 Ventana® antibody, as today a univocal validated and accredited immunohistochemical procedure does not exist, to preliminary detect BRAF status in our routine diagnostic procedures...
November 18, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27849631/reduced-h3k27me3-expression-is-common-in-nodular-melanomas-of-childhood-associated-with-congenital-melanocytic-nevi-but-not-in-proliferative-nodules
#7
Klaus J Busam, Kara N Shah, Pedram Gerami, Thomas Sitzman, Achim A Jungbluth, Veronica Kinsler
The formation of a nodule within a congenital melanocytic nevus (CMN) raises concerns about possible melanoma. Most new nodular growths that develop during childhood, however, are benign proliferative nodules (PN); melanoma is very rare. The distinction of melanoma from PN can at times be difficult clinically and histopathologically, requiring ancillary molecular tests for diagnosis. Although the application of molecular methods has revealed new insights into the mutational and genomic landscape of childhood melanomas, little is known about epigenetic events that may drive the growth of a melanoma or PN in a CMN...
November 15, 2016: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/27846726/-new-technologies-for-in-vivo-cancer-diagnostics
#8
L Hernychova, D Coufalová, E Michalova, R Nenutil, B Vojtěšek
BACKGROUND: The treatment of oncological diseases is based on the combination of surgery, representing the key step for the removal of the tumor tissue, radiotherapy, chemotherapy, and hormone therapy. However, the surgery is often accompanied by issue of determining the boundaries of the tumor. Prior the operation, the surgeon has information on preoperative findings, which indicate the location and extent of the tumor, but does not specify a clear boundary between the tumor and healthy tissue...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/27788045/mitogen-activated-protein-kinase-signaling-pathway-in-cutaneous-melanoma-an-updated-review
#9
Andres Martin Acosta, ShriHari S Kadkol
The mitogen-activated protein kinase (MAPK) signaling pathway is a cascade of protein kinases that act in a sequential and predominantly linear fashion, albeit displaying some cross talk with other signaling cascades. Mutations in proteins integral to the MAPK signaling pathway are present in more than 50% of cutaneous melanomas. The most frequently mutated protein is v-raf murine sarcoma viral oncogene homolog B (BRAF), followed by neuroblastoma Ras viral oncogene homolog (NRAS). Recently, the development of targeted drugs for the treatment of BRAF-mutant melanoma has led to the widespread implementation of molecular assays for the detection of specific BRAF mutations...
November 2016: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/27748184/177lu-dota-bevacizumab-radioimmunotherapy-agent-for-melanoma
#10
Ximena Camacho, Victoria Calzada, Marcelo Fernández, Omar Alonso, Roger Chammas, Eloisa Riva, Juan Pablo Gambini, Pablo Cabral
BACKGROUND: Vascular endothelial growth factor (VEGF) is one of the classic factors to tumor-induced angiogenesis in several types, including melanoma. Bevacizumab is a humanized monoclonal antibody directed against VEGF. OBJECTIVE: To radiolabel Bevacizumab with 177-Lutetium as a potential radioimmunotherapy agent for melanoma. METHODS: Bevacizumab was derivatized with DOTA-NHS-ester at 4 ºC for 18 h. DOTA-Bevacizumab was radiolabeled with 177LuCl3 (15 MBq/mg) at 37 ºC for 1 h...
October 10, 2016: Current Radiopharmaceuticals
https://www.readbyqxmd.com/read/27709959/64cu2-ions-as-pet-probe-an-emerging-paradigm-in-molecular-imaging-of-cancer
#11
Rubel Chakravarty, Sudipta Chakraborty, Ashutosh Dash
Positron emission tomography (PET) imaging has transformed diagnostic nuclear medicine and become an essential strategy in cancer management. With the expected growth of this molecular imaging modality, there is a recognized need for new PET probes to address the clinical challenges in the early diagnosis and staging of various types of cancers. In this endeavor, the prospect of using 64Cu in the form of simple Cu2+ ions as PET probe is not only a cost-effective proposition, but also seems poised to broaden the palette of molecular imaging probes in the foreseeable future...
October 6, 2016: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27707590/development-and-validation-of-a-noninvasive-2-gene-molecular-assay-for-cutaneous-melanoma
#12
Pedram Gerami, Zuxu Yao, David Polsky, Burkhard Jansen, Klaus Busam, Jonhan Ho, Mary Martini, Laura K Ferris
BACKGROUND: Clinical and histopathologic assessment of pigmented skin lesions remains challenging even for experts. Differentiated and accurate noninvasive diagnostic modalities are highly desirable. OBJECTIVE: We sought to provide clinicians with such a tool. METHODS: A 2-gene classification method based on LINC00518 and preferentially expressed antigen in melanoma (PRAME) gene expression was evaluated and validated in 555 pigmented lesions (157 training and 398 validation samples) obtained noninvasively via adhesive patch biopsy...
October 1, 2016: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/27548802/a-melanin-bleaching-methodology-for-molecular-and-histopathological-analysis-of-formalin-fixed-paraffin-embedded-tissue
#13
Joon-Yong Chung, Jiyeon Choi, John D Sears, Kris Ylaya, Candice Perry, Chel H Choi, Seung-Mo Hong, Hanbyoul Cho, Kevin M Brown, Stephen M Hewitt
Removal of excessive melanin from heavily pigmented formalin-fixed paraffin-embedded (FFPE) melanoma tissues is essential for histomorphological and molecular diagnostic assessments. Although there have been efforts to address this issue, current methodologies remain complex and time-consuming, and are not suitable for multiple molecular applications. Herein, we have developed a robust and rapid melanin-bleaching methodology for FFPE tissue specimens. Our approach is based on quick bleaching (15 min) at high temperature (80 °C) with 0...
October 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27505074/analytical-characteristics-of-a-noninvasive-gene-expression-assay-for-pigmented-skin-lesions
#14
Zuxu Yao, Talisha Allen, Margaret Oakley, Carol Samons, Darryl Garrison, Burkhard Jansen
We previously reported clinical performance of a novel noninvasive and quantitative PCR (qPCR)-based molecular diagnostic assay (the pigmented lesion assay; PLA) that differentiates primary cutaneous melanoma from benign pigmented skin lesions through two target gene signatures, LINC00518 (LINC) and preferentially expressed antigen in melanoma (PRAME). This study focuses on analytical characterization of this PLA, including qPCR specificity and sensitivity, optimization of RNA input in qPCR to achieve a desired diagnostic sensitivity and specificity, and analytical performance (repeatability and reproducibility) of this two-gene PLA...
August 2016: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/27488807/a-comparison-of-immunohistochemical-and-molecular-methods-used-for-analyzing-the-braf-v600e-gene-mutation-in-malignant-melanoma-in-taiwan
#15
Wen-Kuan Huang, Tseng-Tong Kuo, Chiao-En Wu, Hsin-Yi Cheng, Chia-Hsun Hsieh, Jia-Juan Hsieh, Yung-Chi Shen, Ming-Mo Hou, Todd Hsu, John Wen-Cheng Chang
AIMS: The BRAF V600 mutation has been shown to be clinically meaningful in terms of both the prognosis and sensitivity of BRAF inhibitors in patients with metastatic melanoma. Recently, a BRAF V600E mutation-specific antibody, VE1, was generated for the detection of tumors bearing BRAF V600E mutations. To determine the clinical value of immunohistochemical testing, we compared the prevalence of mutant BRAF detected by VE1 with direct sequencing results. METHODS: Paraffin-embedded, formalin-fixed melanoma biopsies were analyzed for the BRAF mutation status by immunohistochemistry with the VE1 antibody...
August 4, 2016: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/27488299/molecular-markers-and-targeted-therapeutics-in-metastatic-tumors-of-the-spine-changing-the-treatment-paradigms
#16
C Rory Goodwin, Nancy Abu-Bonsrah, Laurence D Rhines, Jorrit-Jan Verlaan, Mark H Bilsky, Ilya Laufer, Stefano Boriani, Daniel M Sciubba, Chetan Bettegowda
STUDY TYPE: A review of the literature. OBJECTIVE: The aim of this study was to discuss the evolution of molecular signatures and the history and development of targeted therapeutics in metastatic tumor types affecting the spinal column. SUMMARY OF BACKGROUND DATA: Molecular characterization of metastatic spine tumors is expected to usher in a revolution in diagnostic and treatment paradigms. Molecular characterization will provide critical information that can be used for initial diagnosis, prognosticating the ideal treatment strategy, assessment of treatment efficacy, surveillance and monitoring recurrence, and predicting complications, clinical outcome, and overall survival in patients diagnosed with metastatic cancers to the spinal column...
October 15, 2016: Spine
https://www.readbyqxmd.com/read/27465194/malignant-melanoma-beyond-the-basics
#17
Sabrina N Pavri, James Clune, Stephan Ariyan, Deepak Narayan
LEARNING OBJECTIVES: After reading this article, the participant should be able to: 1. Discuss the initial management of cutaneous malignant melanoma with regard to diagnostic biopsy and currently accepted resection margins. 2. Be familiar with the management options for melanoma in specific situations such as subungual melanoma, auricular melanoma, and melanoma in the pregnant patient. 3. Discuss the differentiating characteristics of desmoplastic melanoma and its treatment options. 4...
August 2016: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/27439913/nras-q61k-mutated-primary-leptomeningeal-melanoma-in-a-child-case-presentation-and-discussion-on-clinical-and-diagnostic-implications
#18
Giulia Angelino, Maria Debora De Pasquale, Luigi De Sio, Annalisa Serra, Luca Massimi, Rita De Vito, Antonio Marrazzo, Laura Lancella, Andrea Carai, Manila Antonelli, Felice Giangaspero, Marco Gessi, Laura Menchini, Laura Scarciolla, Daniela Longo, Angela Mastronuzzi
BACKGROUND: Primary melanocytic neoplasms are rare in the pediatric age. Among them, the pattern of neoplastic meningitis represents a peculiar diagnostic challenge since neuroradiological features may be subtle and cerebrospinal fluid analysis may not be informative. Clinical misdiagnosis of neoplastic meningitis with tuberculous meningitis has been described in few pediatric cases, leading to a significant delay in appropriate management of patients. We describe the case of a child with primary leptomeningeal melanoma (LMM) that was initially misdiagnosed with tuberculous meningitis...
2016: BMC Cancer
https://www.readbyqxmd.com/read/27408703/recent-advances-in-molecular-genetics-of-melanoma-progression-implications-for-diagnosis-and-treatment
#19
REVIEW
Iwei Yeh
According to the multi-step carcinogenesis model of cancer, initiation results in a benign tumor and subsequent genetic alterations lead to tumor progression and the acquisition of the hallmarks of cancer. This article will review recent discoveries in our understanding of initiation and progression in melanocytic neoplasia and the impact on diagnostic dermatopathology.
2016: F1000Research
https://www.readbyqxmd.com/read/27387384/a-unique-chromosomal-in-frame-deletion-identified-among-seven-xp-c-patients
#20
Steffen Schubert, Petra Rieper, Andreas Ohlenbusch, Christina Seebode, Janin Lehmann, Alexei Gratchev, Steffen Emmert
BACKGROUND: The nucleotide excision repair (NER) pathway, defective in xeroderma pigmentosum (XP) patients, removes DNA photolesions in order to prevent carcinogenesis. Complementation group C (XP-C) is the most frequent group of XP patients worldwide. METHODS: We analyzed seven XP-C patients clinically and molecular-genetically applying: post-UV cell survival (MTT-assay), quantitative Real-time PCR, sequencing on chromosomal as well as cDNA level, and in silico interpretation of sequencing data...
September 2016: Photodermatology, Photoimmunology & Photomedicine
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