Premium
Immunohistochemical analysis of T‐type calcium channels in acquired melanocytic naevi and melanoma
Author(s) -
Maiques O.,
Macià A.,
Moreno S.,
Barceló C.,
Santacana M.,
Vea A.,
Herreros J.,
Gatius S.,
Ortega E.,
Valls J.,
Chen B.J.,
LlobetNavas D.,
MatiasGuiu X.,
Cantí C.,
Marti R.M.
Publication year - 2017
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.15121
Subject(s) - melanoma , pten , immunohistochemistry , pathology , nevus , cyclin d1 , cancer research , tissue microarray , medicine , cd31 , biology , cell cycle , cancer , pi3k/akt/mtor pathway , signal transduction , biochemistry
Summary Background Cutaneous malignant melanoma arises from transformed melanocytes de novo or from congenital or acquired melanocytic naevi. We have recently reported that T‐type Ca 2+ channels ( TT ‐Cs) are upregulated in human melanoma and play an important role in cell proliferation. Objectives To describe for the first time in formalin‐fixed paraffin‐embedded tissue the immunoexpression of TT ‐Cs in biopsies of normal skin, acquired melanocytic naevi and melanoma, in order to evaluate their role in melanomagenesis and/or tumour progression, their utility as prognostic markers and their possible use in targeted therapies. Methods Tissue samples from normal skin, melanocytic naevi and melanoma were subjected to immunohistochemistry for two TT ‐Cs (Cav3.1, Cav3.2); markers of proliferation (Ki67), the cell cycle (cyclin D1), hypoxia (Glut1), vascularization ( CD 31) and autophagy ( LC 3); BRAF V600E mutation ( VE 1) and phosphatase and tensin homologue ( PTEN ). Immunostaining was evaluated by histoscore. In silico analysis was used to assess the prognostic value of TT ‐C overexpression. Results TT ‐C immunoexpression increased gradually from normal skin to common naevi, dysplastic naevi and melanoma samples, but with differences in the distribution of both isoforms. Particularly, Cav3.2 expression was significantly higher in metastatic melanoma than in primary melanoma. Statistical correlation showed a linear interaction between PTEN loss/ BRAF V600E/Cav3.1/ LC 3/ Ki67/cyclin D1/Cav3.2/Glut1. Disease‐free survival ( DFS ) and overall survival correlated inversely with overexpression of Cav3.2. DFS also correlated inversely with overexpression of Cav3.1. Conclusions TT ‐C immunoexpression on melanocytic neoplasms is consistent with our previous in vitro studies and appears to be related to tumour progression. TT ‐C upregulation can be considered as a prognostic marker using The Cancer Genome Atlas database. The high expression of Cav3.2 in metastatic melanoma encourages the investigation of the use of TT ‐C blockers in targeted therapies.