PMID- 27718503
OWN - NLM
STAT- MEDLINE
DCOM- 20180326
LR  - 20180326
IS  - 1365-2133 (Electronic)
IS  - 0007-0963 (Linking)
VI  - 176
IP  - 5
DP  - 2017 May
TI  - Immunohistochemical analysis of T-type calcium channels in acquired melanocytic
      naevi and melanoma.
PG  - 1247-1258
LID - 10.1111/bjd.15121 [doi]
AB  - 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 (CD31) and
      autophagy (LC3); BRAF V600E mutation (VE1) 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/LC3/ 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.
CI  - (c) 2016 British Association of Dermatologists.
FAU - Maiques, O
AU  - Maiques O
AD  - University of Lleida, IRBLleida, Lleida, Spain.
FAU - Macia, A
AU  - Macia A
AD  - University of Lleida, IRBLleida, Lleida, Spain.
FAU - Moreno, S
AU  - Moreno S
AD  - Department of Dermatology, Hospital Universitari Arnau de Vilanova; University of
      Lleida, IRBLleida, Lleida, Spain.
FAU - Barcelo, C
AU  - Barcelo C
AD  - University of Lleida, IRBLleida, Lleida, Spain.
FAU - Santacana, M
AU  - Santacana M
AD  - Department of Pathology and Molecular Genetics, Hospital Universitari Arnau de
      Vilanova; University of Lleida, IRBLleida, Lleida, Spain.
FAU - Vea, A
AU  - Vea A
AD  - Department of Dermatology, Hospital Universitari Arnau de Vilanova; University of
      Lleida, IRBLleida, Lleida, Spain.
FAU - Herreros, J
AU  - Herreros J
AD  - University of Lleida, IRBLleida, Lleida, Spain.
FAU - Gatius, S
AU  - Gatius S
AD  - Department of Pathology and Molecular Genetics, Hospital Universitari Arnau de
      Vilanova; University of Lleida, IRBLleida, Lleida, Spain.
FAU - Ortega, E
AU  - Ortega E
AD  - Department of Oncology, Hospital Universitari Arnau de Vilanova; University of
      Lleida, IRBLleida, Lleida, Spain.
FAU - Valls, J
AU  - Valls J
AD  - Biostatistics Unit, IRBLleida, Lleida, Spain.
FAU - Chen, B J
AU  - Chen BJ
AD  - New York Genome Center, New York, NY, U.S.A.
FAU - Llobet-Navas, D
AU  - Llobet-Navas D
AD  - Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, U.K.
FAU - Matias-Guiu, X
AU  - Matias-Guiu X
AD  - Department of Pathology and Molecular Genetics, Hospital Universitari Arnau de
      Vilanova; University of Lleida, IRBLleida, Lleida, Spain.
FAU - Canti, C
AU  - Canti C
AD  - University of Lleida, IRBLleida, Lleida, Spain.
FAU - Marti, R M
AU  - Marti RM
AD  - Department of Dermatology, Hospital Universitari Arnau de Vilanova; University of
      Lleida, IRBLleida, Lleida, Spain.
LA  - eng
PT  - Journal Article
DEP - 20170320
PL  - England
TA  - Br J Dermatol
JT  - The British journal of dermatology
JID - 0004041
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (CACNA1G protein, human)
RN  - 0 (CACNA1H protein, human)
RN  - 0 (Calcium Channels, T-Type)
SB  - IM
CIN - Br J Dermatol. 2017 May;176(5):1122. PMID: 28504379
MH  - Biomarkers, Tumor/*metabolism
MH  - Calcium Channels, T-Type/*metabolism
MH  - Cell Proliferation/physiology
MH  - Disease Progression
MH  - Disease-Free Survival
MH  - Humans
MH  - Immunohistochemistry
MH  - Kaplan-Meier Estimate
MH  - Melanoma/*diagnosis/mortality
MH  - Neoplasm Recurrence, Local/etiology
MH  - Nevus, Pigmented/*diagnosis/mortality
MH  - Prognosis
MH  - Skin Neoplasms/*diagnosis/mortality
MH  - Up-Regulation
EDAT- 2016/10/09 06:00
MHDA- 2018/03/27 06:00
CRDT- 2016/10/09 06:00
PHST- 2016/09/26 00:00 [accepted]
PHST- 2016/10/09 06:00 [pubmed]
PHST- 2018/03/27 06:00 [medline]
PHST- 2016/10/09 06:00 [entrez]
AID - 10.1111/bjd.15121 [doi]
PST - ppublish
SO  - Br J Dermatol. 2017 May;176(5):1247-1258. doi: 10.1111/bjd.15121. Epub 2017 Mar
      20.