Universität zu Köln

Al-Nomani, Lukman, Friedrichs, Jacqueline, Schuele, Roland, Buettner, Reinhard and Friedrichs, Nicolaus (2015). Tumoral expression of nuclear cofactor FHL2 is associated with lymphatic metastasis in sporadic but not in HNPCC-associated colorectal cancer. Pathol. Res. Pract., 211 (2). S. 171 - 175. JENA: ELSEVIER GMBH, URBAN & FISCHER VERLAG. ISSN 0344-0338

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Abstract

Background: Four and a half LIM domain protein-2 (FHL2) is part of the focal adhesion structures modulating cell motility. FHL2 may translocate into the nucleus serving as a transcriptional cofactor binding several transcription factors. Overexpression of FHL2 has been linked to cancer progression in various neoplasias. The aim of the present study was to determine, whether FHL2's function as nuclear cofactor plays a prognostic role in invading tumor cells of sporadic and HNPCC-associated colorectal cancer (CRC). Design: Immunohistochemical staining intensity of nuclear FHL2 was quantified by Remmele score analysing 47 sporadic and 42 HNPCC-associated colorectal cancers. Analysis was restricted to carcinoma cells of the tumoral invasion front. Results: Confocal microscopy detected nuclear expression of FHL2 in colon cancer cells and absence of nuclear FHL2 signal in normal colon enterocytes. In colon cancer, nuclear FHL2 expression was predominantly observed in low-differentiated, often mucinous tumor areas. 42.55% of sporadic and 54.76% of HNPCC-associated CRC showed enhanced (Remmele score 6-12) nuclear FHL2 expression in the carcinoma cells of the tumoral advancing edge. Enhanced nuclear FHL2 expression was significantly linked to lymphatic metastasis in sporadic CRC (p = 0.0197) and almost reached significance in HNPCC-associated CRC (p = 0.0545). In contrast, nuclear FHL2 expression was neither associated with hematogenic metastasis in sporadic (p = 0.7087) nor in HNPCC-associated colorectal cancer (p = 0.3007). Conclusions: We recently demonstrated that enhanced nuclear FHL2 expression in tumor stroma of sporadic colon cancer is associated with lymphatic metastasis. The results of the present study indicate a synergistic effect of nuclear cofactor FHL2 in tumor cells as well as in peritumoral stroma cells promoting lymphatic metastasis in sporadic CRC. As HNPCC-associated tumors did not show a significant association between tumoral nuclear FHL2 expression and lymphatic metastasis we speculate, that the intensive lymphocytic immune response in HNPCC precludes a direct contact of tumor cells and stromal cells resulting in reduced lymphatic spread. (C) 2014 Elsevier GmbH. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Al-Nomani, Lukman UNSPECIFIED UNSPECIFIED UNSPECIFIED Friedrichs, Jacqueline UNSPECIFIED UNSPECIFIED UNSPECIFIED Schuele, Roland UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Friedrichs, Nicolaus UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-417066
DOI:	10.1016/j.prp.2014.12.001
Journal or Publication Title:	Pathol. Res. Pract.
Volume:	211
Number:	2
Page Range:	S. 171 - 175
Date:	2015
Publisher:	ELSEVIER GMBH, URBAN & FISCHER VERLAG
Place of Publication:	JENA
ISSN:	0344-0338
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TRANSCRIPTIONAL COACTIVATOR FHL2; EPITHELIAL-MESENCHYMAL TRANSITION; ANDROGEN RECEPTOR; COLON-CANCER; PROSTATE-CANCER; LIM; ALPHA; CARCINOGENESIS; PROTEINS; DOMAIN Multiple languages Pathology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/41706