Expression of erbB-3 protein in colorectal adenocarcinoma: correlation with poor survival

Background/aims: The family of erbB receptors includes four transmembrane g lycoproteins with tyrosine kinase activity. These receptors are widely ex p ressed in normal tissues, but they also have been implicated in the develop ment of several human adenocarcinomas. c-erbB-3/HER-3 has been detected to a greater or lesser extent in many tissues from the digestive, urinary, rep roductive and respiratory tracts. The overexpression of c-erbB-3/HER-3 prot ein has also been shown in 53%-88% of colorectal adenocarcinomas. In this s tudy we investigated the expression of the c-erbB-3/ HER-S gene product in colorectal tumour samples: and compared the results obtained with several c linicopathological parameters, including the survival of patients. Methods: Paraffin-embedded tissue sections were analysed immunohistochemically, usi ng monoclonal antibody RTJ1 to human erbB-3 protein. Antibody RTJ1 specific ity was confirmed by immunoprecipitation followed by Western blotting analy sis. Amplification of the erbB-3 oncogene was tested by dot-blot hybridizat ion. Results: Adenocarcinomas of the colon were positive for erbB-3 protein in 78% of samples examined. Dot-blot analysis showed no amplification of t he erbB-3 gene in colon adenocarcinomas. Statistical analysis showed that p atients with rumours that could not be stained for erbB-3 protein survived significantly longer (P < 0.05) than patients with rumours staining positiv e for the erbB-3 protein. A Cox proportional-hazards model with stepwise va riable selection identified age, sex and erbB-3 expression as important pro gnostic factors. Conclusion: These findings demonstrate that erbB-3 protein expression could serve as a prognostic factor in colorectal malignancies.