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Molecular diagnostic melanoma

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
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
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
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
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
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
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
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
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
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
S Schubert, P Rieper, A Ohlenbusch, C Seebode, J Lehmann, A Gratchev, S 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...
July 7, 2016: Photodermatology, Photoimmunology & Photomedicine
Jie-Fu Chen, Yazhen Zhu, Yi-Tsung Lu, Elisabeth Hodara, Shuang Hou, Vatche G Agopian, James S Tomlinson, Edwin M Posadas, Hsian-Rong Tseng
Liquid biopsy of tumor through isolation of circulating tumor cells (CTCs) allows non-invasive, repetitive, and systemic sampling of disease. Although detecting and enumerating CTCs is of prognostic significance in metastatic cancer, it is conceivable that performing molecular and functional characterization on CTCs will reveal unprecedented insight into the pathogenic mechanisms driving lethal disease. Nanomaterial-embedded cancer diagnostic platforms, i.e., NanoVelcro CTC Assays represent a unique rare-cell sorting method that enables detection isolation, and characterization of CTCs in peripheral blood, providing an opportunity to noninvasively monitor disease progression in individual cancer patients...
2016: Theranostics
Nives Jonjić, Andrea Dekanić, Nedeljka Glavan, Larisa Prpić-Massari, Blaženka Grahovac
A case of a 41-year-old woman with a history of nodular melanoma (NM), associated with an indurated dome-shaped blue-black nodule with a diameter of 1.2 cm in the gluteal region, is presented. Clinical diagnosis of the lesion, present from birth, was blue nevus. Recently, the nodule has been showing a mild enlargement and thus complete resection was performed. Histological analysis revealed a pigmented lesion with an expansive pattern of extension into the dermis and the subcutaneous adipose tissue. The lesion displayed an alveolar pattern as well as a pigmented dendritic cell pattern...
2016: Case Reports in Pathology
Eszter Sári, Hajnalka Rajnai, Kitti Dénes, Csaba Bödör, Judit Csomor, Gábor Körösmezey, Ilona Tárkányi, Hanna Eid, Zsolt Nagy, Judit Demeter
Differential diagnosis of hairy cell leukemia (HCL) and related disorders (hairy cell leukemia variant and splenic marginal zone lymphoma) is of utmost importance since the treatment and prognosis of these lymphomas differ. Since 2011 diagnosis of hairy cell leukemia has been easier because of discovery of the disease defining somatic mutation BRAF V600E mutation, which has been also known as driver mutation in malignant melanoma. The presence of this mutation enabled targeted molecular therapy in HCL as well...
June 6, 2016: Magyar Onkologia
B Schilling, K G Griewank
To provide appropriate therapy and follow-up to patients with malignant melanoma, proper diagnostics are of critical importance. Targeted therapy of advanced melanoma is based on the molecular genetic analyses of tumor tissue. In addition, sequencing of genes and other genetic approaches can provide insight into the origin of melanocytic tumors and can aid in distinguishing benign from malignant lesions. In this regard, spizoid neoplasms remain a challenging entity. Aside from genetic analyses of tumor tissue, immunohistochemistry remains an essential tool in melanoma diagnostics and TNM classification...
July 2016: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
Christine M Lovly, April K S Salama, Ravi Salgia
The rapidly changing landscape of oncology has brought new light, and with it, new challenges to optimizing therapeutic strategies for patients. Although the concept of patient heterogeneity is well known to any practicing clinician, a more detailed understanding of the biologic changes that underscore the clinical picture is beginning to emerge. Thus, tumor heterogeneity has come to encompass more than just the clinical picture and can represent both intratumor and intertumor differences. Within the fields of thoracic oncology and melanoma, the discovery of key molecular drivers has resulted in landmark breakthroughs in therapy...
2016: American Society of Clinical Oncology Educational Book
Nicole Pfarr, Roland Penzel, Frederick Klauschen, Daniel Heim, Regine Brandt, Daniel Kazdal, Moritz Jesinghaus, Esther Herpel, Peter Schirmacher, Arne Warth, Wilko Weichert, Volker Endris, Albrecht Stenzinger
Targeted deep massive parallel sequencing has been implemented in routine molecular diagnostics for high-throughput genetic profiling of formalin-fixed paraffin-embedded (FFPE) cancer samples. This approach is widely used to interrogate simple somatic mutations but experience with the analysis of copy number variations (CNV) is limited. Here, we retrospectively analyzed CNV in 822 cancer cases (135 melanoma, 468 non-small cell lung cancers (NSCLC), 219 colorectal cancers (CRC)). We observed a decreasing frequency of CNV in clinically actionable genes from melanoma to NSCLC to CRC...
November 2016: Genes, Chromosomes & Cancer
Camille Prével, Morgan Pellerano, Juan A González-Vera, Pauline Henri, Laurent Meunier, Julien Vollaire, Véronique Josserand, May C Morris
Melanoma constitutes the most aggressive form of skin cancer, which further metastasizes into a deadly form of cancer. The p16(INK4a)-Cyclin D-CDK4/6-pRb pathway is dysregulated in 90% of melanomas. CDK4/Cyclin D kinase hyperactivation, associated with mutation of CDK4, amplification of Cyclin D or loss of p16(INK4a) leads to increased risk of developing melanoma. This kinase therefore constitutes a key biomarker in melanoma and an emerging pharmacological target, however there are no tools enabling direct detection or quantification of its activity...
November 15, 2016: Biosensors & Bioelectronics
Kathryn G Lindsey, Courtney Ingram, Joseph Bergeron, Jack Yang
Despite increased surveillance and public awareness, the incidence of melanoma is increasing. Frequently, fine-needle aspiration is employed for the diagnosis of metastatic disease, and aspirated material is used for cytogenetic and molecular studies to guide treatment options. The pairing of a significant diagnosis with the numerous morphologic variants of melanoma can make the cytologic evaluation disquieting. We present selected examples of our experiences and a brief review of the literature to provide cytodiagnostic clues for this malignancy...
July 2016: Seminars in Diagnostic Pathology
Priscilla Denise Zepeda-Lopez, Julio Cesar Salas-Alanis, Sonia Toussaint-Caire, Daniela Gutierrez-Mendoza, Elisa Vega-Memije, Saúl Lino Silva, Oscar Raul Fajardo-Ramírez, Gregorio Alcazar, María Guadalupe Moreno-Treviño, Hugo Alberto Barrera Saldaña
BACKGROUND: B-Raf is a serine/threonine protein kinase activating the MAP kinase/ERK-signaling pathway. It has been shown that 50% of melanomas harbor activating BRAF mutations, with over 90% being the V600E mutation. OBJECTIVE: The goal of this research was to determine the prevalence of the BRAF V600E mutation in patients from Central Mexico diagnosed with primary melanoma. METHODS: Skin biopsies from 47 patients with melanoma were obtained from the dermatology department of the Hospital General 'Dr...
January 2016: Case Reports in Oncology
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