Immunohistochemical analysis of T-type calcium channels in acquired melanocytic nevi and melanoma
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...
| Autores: | , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2016 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:10459.1/60518 |
| Acceso en línea: | https://doi.org/10.1111/bjd.15121 http://hdl.handle.net/10459.1/60518 |
| Access Level: | acceso abierto |
| Palabra clave: | Melanoma Immunohistoquímica Canals de calci Histopatologia Immunohistochemistry Calcium channels Pathological histology |
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Immunohistochemical analysis of T-type calcium channels in acquired melanocytic nevi and melanomaMaiques Carlos, OscarMacià Armengol, AnnaMoreno, SaraBarceló Gómez, CarlaSantacana Espasa, MariaVeà Jódar, ÀlvarHerreros Danés, JuditGatius Calderó, SòniaOrtega Izquierdo, Maria EugeniaValls Marsal, JoanChen, Bo-JuenLlovet Navàs, DavidMatias-Guiu, XavierCantí Nicolás, CarlesMartí Laborda, Rosa Ma.MelanomaImmunohistoquímicaCanals de calciHistopatologiaMelanomaImmunohistochemistryCalcium channelsPathological histologyBACKGROUND 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)Wiley Online Library2017201820162017info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://doi.org/10.1111/bjd.15121http://hdl.handle.net/10459.1/60518http://hdl.handle.net/10459.1/60518reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: https://doi.org/10.1111/bjd.15121British Journal of Dermatology, 2016, vol. 176, num. 5, p. 1247-1258(c) British Association of Dermatologists, 2016info:eu-repo/semantics/openAccessoai:recercat.cat:10459.1/605182026-05-29T05:05:01Z |
| dc.title.none.fl_str_mv |
Immunohistochemical analysis of T-type calcium channels in acquired melanocytic nevi and melanoma |
| title |
Immunohistochemical analysis of T-type calcium channels in acquired melanocytic nevi and melanoma |
| spellingShingle |
Immunohistochemical analysis of T-type calcium channels in acquired melanocytic nevi and melanoma Maiques Carlos, Oscar Melanoma Immunohistoquímica Canals de calci Histopatologia Melanoma Immunohistochemistry Calcium channels Pathological histology |
| title_short |
Immunohistochemical analysis of T-type calcium channels in acquired melanocytic nevi and melanoma |
| title_full |
Immunohistochemical analysis of T-type calcium channels in acquired melanocytic nevi and melanoma |
| title_fullStr |
Immunohistochemical analysis of T-type calcium channels in acquired melanocytic nevi and melanoma |
| title_full_unstemmed |
Immunohistochemical analysis of T-type calcium channels in acquired melanocytic nevi and melanoma |
| title_sort |
Immunohistochemical analysis of T-type calcium channels in acquired melanocytic nevi and melanoma |
| dc.creator.none.fl_str_mv |
Maiques Carlos, Oscar Macià Armengol, Anna Moreno, Sara Barceló Gómez, Carla Santacana Espasa, Maria Veà Jódar, Àlvar Herreros Danés, Judit Gatius Calderó, Sònia Ortega Izquierdo, Maria Eugenia Valls Marsal, Joan Chen, Bo-Juen Llovet Navàs, David Matias-Guiu, Xavier Cantí Nicolás, Carles Martí Laborda, Rosa Ma. |
| author |
Maiques Carlos, Oscar |
| author_facet |
Maiques Carlos, Oscar Macià Armengol, Anna Moreno, Sara Barceló Gómez, Carla Santacana Espasa, Maria Veà Jódar, Àlvar Herreros Danés, Judit Gatius Calderó, Sònia Ortega Izquierdo, Maria Eugenia Valls Marsal, Joan Chen, Bo-Juen Llovet Navàs, David Matias-Guiu, Xavier Cantí Nicolás, Carles Martí Laborda, Rosa Ma. |
| author_role |
author |
| author2 |
Macià Armengol, Anna Moreno, Sara Barceló Gómez, Carla Santacana Espasa, Maria Veà Jódar, Àlvar Herreros Danés, Judit Gatius Calderó, Sònia Ortega Izquierdo, Maria Eugenia Valls Marsal, Joan Chen, Bo-Juen Llovet Navàs, David Matias-Guiu, Xavier Cantí Nicolás, Carles Martí Laborda, Rosa Ma. |
| author2_role |
author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Melanoma Immunohistoquímica Canals de calci Histopatologia Melanoma Immunohistochemistry Calcium channels Pathological histology |
| topic |
Melanoma Immunohistoquímica Canals de calci Histopatologia Melanoma Immunohistochemistry Calcium channels Pathological histology |
| description |
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. |
| publishDate |
2016 |
| dc.date.none.fl_str_mv |
2016 2017 2017 2018 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion |
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article |
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acceptedVersion |
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https://doi.org/10.1111/bjd.15121 http://hdl.handle.net/10459.1/60518 http://hdl.handle.net/10459.1/60518 |
| url |
https://doi.org/10.1111/bjd.15121 http://hdl.handle.net/10459.1/60518 |
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Inglés |
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Inglés |
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Versió postprint del document publicat a: https://doi.org/10.1111/bjd.15121 British Journal of Dermatology, 2016, vol. 176, num. 5, p. 1247-1258 |
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(c) British Association of Dermatologists, 2016 info:eu-repo/semantics/openAccess |
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(c) British Association of Dermatologists, 2016 |
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openAccess |
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application/pdf |
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Wiley Online Library |
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Wiley Online Library |
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