Investigation of a possible link between epithelial four-and-a-half LIM domains protein 2 expression and prognosis in colorectal cancer.

Abstract

401 Background: Four-and-a-half LIM domains protein 2 (FHL2) is a component of the focal adhesion structures and has been suggested to play a role in cancer progression. It has been shown to be overexpressed in colorectal cancer (CRC). Here we examined a possible prognostic value of FHL2 in CRC. Methods: Immunohistochemistry for FHL2 was performed on 296 CRCs without distant metastases at time of surgery. Staining in the epithelial compartment was quantitatively evaluated using image analysis, and results were related to clinical variables. Antibody specificity was tested using siRNA transfection in hTERT-immortalised myofibroblasts. FHL2 expression was investigated also by Western blotting in sporadic (HT29) and HNPCC-derived (HCT116 and HCT8/E11) colon cancer cell lines. Results: Varying degrees of cytoplasmic FHL2 expression by neoplastic epithelial cells were detectable in all cases. Higher FHL2 expression in the epithelial compartment was an independent adverse prognostic factor. Expression in the tumour invasion front (p < 0.001) as well as in the centre of the tumour (p < 0.001) was associated with metachronous metastases. No relation between FHL2 expression and microsatellite instability could be demonstrated. Conclusions: Higher FHL2 expression is involved in CRC progression and correlates with the development of metachronous metastases, suggesting that FHL2 is an independent adverse prognostic indicator for CRC.