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:
CreatorsEmailORCIDORCID Put Code
Westphal, PhilippUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mauch, CorneliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Florin, AlexandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Czerwitzki, JacquelineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Olligschlaeger, NinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wodtke, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schuele, RolandUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buettner, ReinhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Friedrichs, NicolausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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:
KeywordsLanguage
BETA-INDUCED TGFBI; ANDROGEN RECEPTOR; PROTEIN FHL2; CANCER PROGRESSION; PROSTATE-CANCER; COLON-CANCER; LIM; COACTIVATOR; CELLS; DIFFERENTIATIONMultiple languages
PathologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/41356

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