Can the clinical outcome in stage II colon carcinomas be predicted by determination of molecular marker expression?

Background: Conventional staging procedures are often unable to precisely predict prognosis in colon cancer (CC). In this study, we set out to investigate the possible role of molecular/structural indicators involved in cell cycle regulation (Ki-67, p53), apoptosis (p53 and bcl-2) and tumour neoangiogenesis (anti-VIII factor) in predicting tumour behaviour and clinical outcome in stage II CC patients. Experimental design: Analysis of the above indicators was performed by immunohistochemistry on 162 CC patient samples with curative intention surgery. Clinicopathological data included tumour grade, vascular and nervous invasion, production of mucin, lymphatic permeation and carcinoembryonic antigen levels. Results: p53 protein was overexpressed in 58%, bcl-2 overexpression in 21.5%, Ki-67 in 60.1% and anti-VIII factor stained positive in 40.16% of the cases. Multiple regression analysis showed that some molecular markers were correlated. A significant relationship was seen between p53 and Ki-67, and bcl-2 and p53, but there was no correlation between bcl2 and Ki-67 overexpression. Stepwise regression selected Ki-67 and anti-VIII factor as the best combination of variables capable of predicting both disease-specific and disease-free survival. Conclusions: Only Ki-67 and anti-VIII factor were shown to be useful for the prediction of outcome and recurrence rate in curatively treated CC patients. In conjunction with clinical and pathological staging, they may provide a stronger indication of clinical outcome than staging alone and help better select therapeutic options in CC patients.