In:
American Journal of Clinical Pathology, Oxford University Press (OUP), Vol. 143, No. 2 ( 2015-02-01), p. 248-256
Abstract:
This study examines the expression and the role of four-and-a-half LIM domains protein 2 (FHL2) and transforming growth factor β1 (TGF-β1) in human malignant melanoma. It is determined whether both proteins influence melanoma survival time. Methods: We analyzed the immunohistochemical staining intensities of FHL2 and TGF-β1 in normal skin and in 50 malignant melanomas with different mutation status (BRAF-V600E, NRAS codon 61 mutation, and wild type). Survival data were available for 45 cases. Results: In melanocytes of nonneoplastic human skin, FHL2 expression was absent. In contrast, 38 (76%) of 50 melanomas showed strong cytoplasmic and partly nuclear FHL2 expression. At the invasion front, cytoplasmic TGF-β1 staining was observed in 32 (64%) of 50 melanomas, and a correlation of FHL2 and TGF-β1 staining intensities was detectable. In follow-up analyses, enhanced FHL2 and TGF-β1 staining intensities in the tumor invasion front were associated with poor survival. Conclusions: Enhanced FHL2 and TGF-β1 expression is correlated with poor survival in human malignant melanoma. Protumorigenic effects of autocrine TGF-β1 secretion might be exerted by induction of FHL2 expression in melanoma cells. Since melanomas treated with targeted therapies often do not show sufficient response rates, inhibition of FHL2 and/or TGF-β1 might be a promising therapeutic approach.
Type of Medium:
Online Resource
ISSN:
1943-7722
,
0002-9173
DOI:
10.1309/AJCPXEC6CIT2TXAF
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2015
detail.hit.zdb_id:
2039921-2