P53 and EGFR expression in colorectal cancer: a reappraisal of 'old' tissue markers in patients with long follow-up.

Background: Extensive research into the biology of colorectal cancer has identified a plethora of molecular markers reputed to provide prognostic information. During the last two decades conflicting results have been drawn on the role of the p53 tumour suppressor gene and of the first identified member of the type receptor tyrosine kinase family, EGFR, on colorectal cancer prognosis, p53 Mutational status has been associated with both improved and reduced survival. EGFR has been associated with reduced length of survival, increasing Dukes' stage and lymph node metastases in several reports, but as many studies have reported no association with unfavourable prognostic parameters. The aim of this study was to evaluate the p53 and EGFR expression in patients with an at least 5-year follow-up.

Patients And Methods: Paraffin-embedded material was retrospectively collected from 164 colorectal adenocarcinoma (50 rectal) patients, who had been operated on between 1994 and 2003. The median follow-up was 5 years (range: 1-14). p53 and EGFR expression were evaluated by immunohistochemistry.

Results: Positive p53 immunostaining and EGFR expression was observed in 63.4% and 43.9% of patients, respectively. p53 and EGFR positivity rates were significantly interrelated (p = 0.004). No significant correlation was found with the examined clinicopathological parameters except for advanced T-stage, which demonstrated significant associations with p53 expression (p = 0.004), EGFR expression (p = 0.0001) and p53/EGFR coexpression (p = 0.001). In univariate survival analysis (log rank test), stage (p = 0.0001), lymphovascular invasion (p = 0.005) and perineural infiltration (p = 0.004) were associated with the overall cancer-specific survival, while a trend existed for EGFR (p = 0.06) and p53/EGFR coexpression (p = 0.07). On multivariate analysis, only stage was associated with increased risk of cancer death (Cox regression analysis p = 0.0001, b-coefficient (SE): 1.898 (0.383).

Conclusion: p53 and EGFR were overexpressed in this colorectal cancer patient population and were significantly associated with advanced T stage. In the context of new therapeutic strategies using EGFR-targeted therapies, although EGFR remains a controversial prognostic factor, this expression-stage association may play a crucial role in a decision to initiate an adjuvant treatment.