Universität zu Köln

Westphal, Philipp, Mauch, Cornelia, Florin, Alexandra, Czerwitzki, Jacqueline, Olligschlaeger, Nina, Wodtke, Claudia, Schuele, Roland, Buettner, Reinhard and Friedrichs, Nicolaus (2015). Enhanced FHL2 and TGF-beta 1 Expression Is Associated With Invasive Growth and Poor Survival in Malignant Melanomas. Am. J. Clin. Pathol., 143 (2). S. 248 - 257. CHICAGO: AMER SOC CLINICAL PATHOLOGY. ISSN 1943-7722

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Abstract

Objectives: This study examines the expression and the role offour-and-a-half LIM domains protein 2 (FHL2) and transforming growth factor beta 1 (TGF-beta 1) 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-beta 1 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-beta 1 staining was observed in 32 (64%) of 50 melanomas, and a correlation of FHL2 and TGF-beta 1 staining intensities was detectable. In follow-up analyses, enhanced FHL2 and TGF-beta 1 staining intensities in the tumor invasion front were associated with poor survival. Conclusions: Enhanced FHL2 and TGF-beta 1 expression is correlated with poor survival in human malignant melanoma. Protumorigenic effects of autocrine TGF-beta 1 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-beta 1 might be a promising therapeutic approach.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Westphal, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Mauch, Cornelia UNSPECIFIED UNSPECIFIED UNSPECIFIED Florin, Alexandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Czerwitzki, Jacqueline UNSPECIFIED UNSPECIFIED UNSPECIFIED Olligschlaeger, Nina UNSPECIFIED UNSPECIFIED UNSPECIFIED Wodtke, Claudia UNSPECIFIED UNSPECIFIED UNSPECIFIED Schuele, Roland UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Friedrichs, Nicolaus UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-413562
DOI:	10.1309/AJCPXEC6CIT2TXAF
Journal or Publication Title:	Am. J. Clin. Pathol.
Volume:	143
Number:	2
Page Range:	S. 248 - 257
Date:	2015
Publisher:	AMER SOC CLINICAL PATHOLOGY
Place of Publication:	CHICAGO
ISSN:	1943-7722
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BETA-INDUCED TGFBI; ANDROGEN RECEPTOR; PROTEIN FHL2; CANCER PROGRESSION; PROSTATE-CANCER; COLON-CANCER; LIM; COACTIVATOR; CELLS; DIFFERENTIATION Multiple languages Pathology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/41356