Apoptosis and cell-cycle regulatory proteins in colorectal carcinoma: relationship to tumour stage and patient survival

The quantitative assessment of apoptotic index (AI) and mitotic index (MI) and the immunoreactivity of p53, bcl-2, p21, and mdm2 were examined in tumour and adjacent normal tissue samples from 30 patients with colonic and 22 with rectal adenocarcinoma. Individual features and combined profiles were correlated with clinicopathological parameters and patient survival data to assess their prognostic value. Increased AI was significantly associated with increased bcl-2 expression (p<0.008) and the immunoprofiles that included bcl-2, but not with MI, p53, p21 or mdm2. AI was significantly associated with increased Dukes' stage from A, B to C (p<0.02) but not D, while MI showed a significant association with all Dukes' stages (p<0.05). No significant association was found between either AI or MI and prognosis. p53, p21, mdm2, and bcl-2 positivity were detected in 65.4%, 53.8%, 65.4%, and 34.6% of cases, respectively. mdm2 was significantly associated with p53 (p<0.03) and p21 (p<0.04) expression and p53 immunoreactivity was more prevalent in rectal tumours (p<0.008). In univariate survival analysis, bcl-2 overexpression was associated with more favourable patient survival (p<0.03). Positive combined patterns p53+/p21+/bcl-2+ and p21+/mdm2+/bcl-2+ (p<0.005); p53+/bcl-2+, p21+/bcl-2+, and mdm2+/bcl-2+ (p<0.01); and p53+/p21+ (p<0.02) were also associated with favourable clinical outcome. In multivariate Cox survival analysis, bcl-2 (p<0.016) and Dukes' stage (p<0.0001) were the only significant independent prognostic indicators. In conclusion, bcl-2 immunoreactivity was associated with apoptosis and could be used in combination with Dukes' stage as a means of predicting prognosis in colorectal cancer.