Immunohistochemical analysis of T-type calcium channels in acquired melanocytic naevi and melanoma
| العنوان: | Immunohistochemical analysis of T-type calcium channels in acquired melanocytic naevi and melanoma |
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| المؤلفون: | Oscar Maiques, Sonia Gatius, B.J. Chen, Carles Cantí, Joan Valls, Carla Barceló, Alvar Vea, David Llobet-Navas, Rosa M. Martí, Eugenia Ortega, Judit Herreros, Xavier Matias-Guiu, Sara Moreno, Anna Macià, Maria Santacana |
| المصدر: | Recercat. Dipósit de la Recerca de Catalunya instname ResearcherID Repositorio Abierto de la UdL Universitad de Lleida |
| بيانات النشر: | Oxford University Press (OUP), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Pathology, medicine.medical_specialty, Skin Neoplasms, Immunohistoquímica, Canals de calci, Kaplan-Meier Estimate, Dermatology, Disease-Free Survival, Calcium Channels, T-Type, 03 medical and health sciences, 0302 clinical medicine, Cyclin D1, Biomarkers, Tumor, medicine, Humans, Nevus, PTEN, Melanoma, neoplasms, Cell Proliferation, Nevus, Pigmented, biology, business.industry, Cell cycle, Prognosis, Pathological histology, medicine.disease, Immunohistochemistry, Up-Regulation, Histopatologia, Calcium channels, 030104 developmental biology, Tumor progression, 030220 oncology & carcinogenesis, Disease Progression, biology.protein, Neoplasm Recurrence, Local, business, V600E |
| الوصف: | BACKGROUND AND OBJECTIVES: Cutaneous malignant melanoma arises from transformed melanocytes de novo or from congenital or acquired melanocytic nevi. We have recently reported that T-type Ca2+ channels (TTCs) are upregulated in human melanoma and play an important role on cell proliferation. The aim of this study was to describe for the first time in formalin-fixed-paraffin-embedded tissue the immunoexpression of TT-Cs in biopsies of normal skin, acquired melanocytic nevi and melanoma, in order to evaluate their role in melanomagenesis and/or tumor progression, their utility as prognostic markers and their possible use in targeted therapies. METHODS: Tissue samples from normal skin, melanocytic nevi and melanoma were subjected to immunohistochemistry for two TT-Cs (Cav3.1, Cav3.2), markers of proliferation (Ki67), cell cycle (Cyclin D1), hypoxia (Glut1), vascularization (CD31) and autophagy (LC3), V600E/BRAF mutation (VE-1) and PTEN. Immunostaining was evaluated by histoscore. In silico analysis was used to assess the prognostic value of TT-Cs over-expression. RESULTS: TT-Cs immunoexpression increased gradually from normal skin to common nevi, dysplastic nevi and melanoma samples, but with differences in distribution of both isoforms. Particularly, Cav3.2 expression was significantly higher in metastatic melanoma than in primary melanoma. Statistical correlation showed a lineal interaction between PTEN-loss/ V600E-BRAF/ Cav3.1/ LC3/ Ki67/ Cyclin D1/ Cav3.2 /Glut1. Disease-free survival (DFS) and global survival (OS) correlated inversely with over-expression of Cav3.2. DFS also correlated inversely with over-expresion of Cav3.1. DISCUSSION: TT-Cs immunoexpression on melanocytic neoplasms 1) is consistent with our previous in vitro studies, 2) appears related to tumor progression, and 3) TT-Cs upregulation can be considered as a prognostic marker using TCGA database. The high expression of Cav3.2 in metastatic melanoma encourages the investigation of the use of TT-Cs blockers in targeted therapies. This article is protected by copyright. All rights reserved. This study was supported by grants from ISCIII (FIS-PI1200260 to R.M.M., FIS-PI1301980 to J.H. and RETICS-RD12/0036/0013 to X.M.G.); from Fundació la Marató de TV3 (FMTV 201331-31 to R.M.M.) and from Generalitat de Catalunya (2014/SGR138 to X.M.-G.) and was cofinanced by FEDER ‘Una manera de hacer Europa’. O.M. and C.B. hold predoctoral fellowships from the University of Lleida and S.M. a predoctoral fellowship from IRBLleida/Diputació de Lleida. Tumour samples were obtained with the support of Xarxa de Bancs de Tumors de Catalunya, sponsored by Pla Director d'Oncología de Catalunya (XBTC), IRBLleida Biobank (B.0000682) and PLATAFORMA BIOBANCOS (PT13/0010/0014) |
| وصف الملف: | application/pdf |
| تدمد: | 0007-0963 |
| DOI: | 10.1111/bjd.15121 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6f03ddd061d4b807092612aa95f2660e https://doi.org/10.1111/bjd.15121 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6f03ddd061d4b807092612aa95f2660e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00070963 |
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| DOI: | 10.1111/bjd.15121 |