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dc.contributor.authorMaiques Carlos, Oscar
dc.contributor.authorMacià Armengol, Anna
dc.contributor.authorMoreno, Sara
dc.contributor.authorBarceló Gómez, Carla
dc.contributor.authorSantacana Espasa, Maria
dc.contributor.authorVeà Jódar, Àlvar
dc.contributor.authorHerreros Danés, Judit
dc.contributor.authorGatius Calderó, Sònia
dc.contributor.authorOrtega Izquierdo, Maria Eugenia
dc.contributor.authorValls Marsal, Joan
dc.contributor.authorChen, Bo-Juen
dc.contributor.authorLlovet Navàs, David
dc.contributor.authorMatias-Guiu, Xavier
dc.contributor.authorCantí Nicolás, Carles
dc.contributor.authorMartí Laborda, Rosa Ma.
dc.date.accessioned2017-11-20T19:28:19Z
dc.date.available2018-03-21T23:32:07Z
dc.date.issued2016-10-08
dc.identifier.issn0007-0963
dc.identifier.urihttp://hdl.handle.net/10459.1/60518
dc.description.abstractBACKGROUND 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.
dc.description.sponsorshipThis 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)
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.publisherWiley Online Library
dc.relation.isformatofVersió postprint del document publicat a: https://doi.org/10.1111/bjd.15121
dc.relation.ispartofBritish Journal of Dermatology, 2016, vol. 176, num. 5, p. 1247-1258
dc.rights(c) British Association of Dermatologists, 2016
dc.subject.classificationMelanoma
dc.subject.classificationImmunohistoquímica
dc.subject.classificationCanals de calci
dc.subject.classificationHistopatologia
dc.subject.otherMelanoma
dc.subject.otherImmunohistochemistry
dc.subject.otherCalcium channels
dc.subject.otherPathological histology
dc.titleImmunohistochemical analysis of T-type calcium channels in acquired melanocytic nevi and melanoma
dc.typeinfo:eu-repo/semantics/article
dc.date.updated2017-11-20T19:28:20Z
dc.identifier.idgrec024817
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.identifier.doihttps://doi.org/10.1111/bjd.15121


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