title: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Verset
authors.forename: J
authors.initials: J
authors.lastname: Tommelein
authors.forename: X
authors.initials: X
authors.lastname: Moles Lopez
authors.forename: C
authors.initials: C
authors.lastname: Decaestecker
authors.forename: M
authors.initials: M
authors.lastname: Mareel
authors.forename: M
authors.initials: M
authors.lastname: Bracke
authors.forename: I
authors.initials: I
authors.lastname: Salmon
authors.forename: O
authors.initials: O
authors.lastname: De Wever
authors.forename: P
authors.initials: P
authors.lastname: Demetter
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D060850:LIM-Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism*; D058628:Myofibroblasts / Q000378:metabolism; D009362:Neoplasm Metastasis; D011379:Prognosis; D034622:RNA Interference; D034741:RNA, Small Interfering; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; C105987:FHL2 protein, human; D060850:LIM-Homeodomain Proteins; D009124:Muscle Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; D051176:beta Catenin