Predicting Adjuvant Chemotherapy Outcome by Simultaneous Analysis of Thymidylate Synthase Expression and p53 Nuclear Accumulation in Colorectal Cancer

Studies have shown that the tumor suppressor gene p53 may regulate thymidylate synthase (TS) activity in colorectal cancer (CRC) cells, hence attributed to chemo-resistance to 5-flurouracil in CRC. In this study, a total of 299 primary CRC patients who underwent surgery alone or received an adjuvant 5-FU-based chemotherapy were retrospectively studied. TS expression and p53 nuclear accumulation on paraffin embedded primary tumor tissue arrays were immunohistochemically assessed, and their relationship to patient overall survival (OS) and disease free survival (DFS) were analyzed. No correlation was found between TS and p53 expression. p53 nuclear accumulation was significantly correlated with tumor location. In all, multivariate analysis shows that TNM stage is a good indicator of patient survival. TS or p53 is not an independent prognostic or predictive factor in the CRCs. In chemotherapy-treated group, simultaneous analysis of TS and p53 indicates patients in the p53−/TS− or p53+/TS+ group have significant better OS and DFS than the group p53−/TS+ or p53+/TS− (P < 0.01). Thus, our study suggests that simultaneous evaluation of both TS and p53 can help to predict the therapeutic effect of CRCs with 5-FU-based adjuvant chemotherapy. Authors contribute equally to this work. Corresponding author.