Differential expression of p53 family proteins in colorectal adenomas and carcinomas: Prognostic and predictive values

Abstract

We studied the contribution of p53 family proteins and their isoforms to the development and progression of colorectal carcinoma in relation to VEGF. Methods: p53, p63, p73 and VEGF proteins were assessed in 45 colorectal adenomas (CRAs), 80 carcinomas (CRCs) and 36 normal colonic tissue samples (NCT) by immunohistochemistry. Different p63 and p73 isoforms were assessed by RT-PCR. Aberrant protein and RNA expressions were correlated to patients' characteristics, disease free and overall survival (DFS& OS). Results: p53, p63, p73 and VEGF proteins were detected in 22.2%, 73.3%, 33.3%, 46.7% CRAs; in 68.8%, 38.8%, 62.5%, 62.5% CRCs and 16.7%, 83.3%; 13.9%, 27.8% NCT (p<0.05 except for VEGF). Commonest isoforms were TAp63a, DNp63, TAp73a in CRA and DNp63, TAp63a, DNp73, TAp73ß in CRC. Significant correlations were found between aggressive tumor phenotypes and aberrations in p73, p53, p63, VEGF. DFS correlated with advanced stage, p73 and VEGF aberrations. While advanced stage, positive lymph nodes, p73 and p53 correlated with OS. Prognosis was worse in patients with aberrant p63& p73 than in those with normal p63& p73 expression regardless of p53 gene status (p<0.05). Conclusions: p53 family proteins and VEGF play a pivotal role in colorectal carcinogenesis. p53 prognostic potential is augmented by p73 and p63 aberrations indicating a synergistic effect between the three family members. Nodal status, stage, p73, VEGF and p53 could be used as predictors of DFS and OS.