Epithelial expression of FHL2 is negatively associated with metastasis-free and overall survival in colorectal cancer

Abstract

Background:Four-and-a-half LIM domains protein 2 (FHL2) is a component of the focal adhesion structures and has been suggested to have a role in cancer progression. It has been shown to be overexpressed in the colorectal cancer (CRC).Methods:Here, we examined a possible prognostic value of FHL2 in CRC. Immunohistochemistry for FHL2 was performed on 296 CRCs without distant metastases at the 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 small-interfering RNA transfection in hTERT-immortalised myofibroblasts.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. Multivariate Cox analysis shows that 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 independently of the clinicopathological variables; expression in the tumour invasion front was also associated with overall survival independently of the clinicopathological variables (P<0.01).Conclusion:Higher FHL2 expression is involved in CRC progression and correlates with the development of metachronous metastases and overall survival, suggesting that FHL2 is an independent adverse prognostic indicator for CRC.

LIM-only protein FHL2 critically determines survival and radioresistance of pancreatic cancer cells

“…5F). Similar to many other cancers originating from prostate, ovary, gastrointestinal tract and the hematopoietic system [38][39][40], FHL2 is overexpressed in PDAC. While PDAC revealed a heterogeneous expression pattern throughout the whole specimen, FHL2 expression was predominant in the central area or invasion front in colorectal cancer in association with metachronous metastases [40] and determined overall survival independent from other clinicopathological variables.…”

“…Similar to many other cancers originating from prostate, ovary, gastrointestinal tract and the hematopoietic system [38][39][40], FHL2 is overexpressed in PDAC. While PDAC revealed a heterogeneous expression pattern throughout the whole specimen, FHL2 expression was predominant in the central area or invasion front in colorectal cancer in association with metachronous metastases [40] and determined overall survival independent from other clinicopathological variables. Moreover, FHL2 directly interacts with the epithelial-tomesenchymal marker Snail1 thereby negatively controlling E-cadherin transcriptional activity in colorectal cancer [41], a finding subsequently connected with TGF-β signaling and invasion [17].…”

Segmentation of glandular epithelium in colorectal tumours to automatically compartmentalise IHC biomarker quantification: A deep learning approach

“…Whole slide scanning and image analysis tools now enable to objectively and quantitatively evaluate IHC biomarkers in a whole tissue slide or a specific region of interest delineated by a pathologist. Compartmentalising the quantitative evaluation of IHC biomarkers in a specific histological structure, such as glandular epithelium in colorectal, breast or prostatic lesions, is often required in histopathology to provide more relevant and informative measurements for clinical research, as evidenced by Verset et al (2013Verset et al ( , 2015. For this purpose, pathologists have to annotate thousands of structures present in histological slide series, a long, tedious and potentially biased task that would greatly benefit from automation.…”

Matrix mechanics controls FHL2 movement to the nucleus to activate p21 expression

“…Moreover, a previous study reported that Rho signaling mediates nuclear localization of FHL2 in NIH 3T3 cells under serum-starved conditions (31). FHL2 is overexpressed in some highly metastatic cell lines and has dramatic effects on cell migration (32)(33)(34). Thus, FHL2 appears to have a number of signaling roles mediating communication between the cytoskeleton and the nucleus, but the molecular steps remain unclear.…”