Abstract
In colorectal cancer, the selection of patients for adjuvant chemotherapy is currently based on the Dukes' stage. However, more prognostic markers are needed to allow better selection of patients whose risk of future recurrence is sufficiently high to warrant chemotherapy. The aims of this study were to investigate the expression and prognostic value of Human Epidermal Growth Factor Receptor-2 (HER-2) and microvessel density (MVD) in patients with colorectal cancer and their relationship with clinico-pathological parameters. HER-2 is over-expressed in a number of epithelial cancers. The prognostic role of HER-2 has been established in breast cancer but remains controversial in colorectal cancer. The expression pattern and prognostic value of HER-2 was investigated in 170 patients with Dukes' B or C colorectal cancer, who underwent radical surgery between 1990 and 1998. The anti-HER-2 monoclonal antibody HM64.13 and a standard avidin-biotin peroxidase detection system were used. Overall, 87% and 41% of cases showed cytoplasmic and membranous HER-2 immunostaining, respectively. In the Dukes' C cancers, a significant survival benefit was observed in those patients whose tumours showed cytoplasmic HER-2 (HR 0.46, Cl95 0.24-0.87), with no association between membranous HER-2 over-expression and clinical outcome. The other independent prognostic factors in the Dukes' C group were apical node metastases, grade 3 tumours, and depth of invasion. No significant prognostic association was seen in the Dukes B patients. Using the monoclonal antibody CD31, MVD did not seem to be a predictor of poor outcome in this study, and there was no association found between MVD and HER-2 overexpression. These data suggest that there may be a correlation between cytoplasmic HER-2 overexpression and better prognostic tumours. Furthermore the high level of membranous HER-2 in colorectal cancer could make it an ideal target for monoclonal antibody-based therapy.