The aim of this study was to evaluate the prognostic value of p53 nuclear accumulation and Bcl-2 expression after curative surgery for rectal cancer. Immunohistochemistry was performed using monoclonal antibodies (MAb) (DO-1 for p53; anti-human Bcl-2 MAb, clone 124, for Bcl-2) on formalin-fixed, paraffin-embedded tissues of 160 rectal carcinomas (UICC stages I III), and results were compared with data from the prospective registry of rectal cancer by univariate and multivariate logistic regression model focusing specifically on recurrence. Survival was calculated by the Kaplan Meier method and proportional hazards model. p53 nuclear accumulation was documented in 39% (n = 63) of tumours and was associated with a higher incidence of tumour progression (local or distant recurrence) and poorer disease-free survival (P < 0.0001). Bcl-2 expression was detected in 29% (n = 47), and was associated with longer disease-free survival and lower incidence of recurrence (P < 0.0086). Multivariate logistic regression analysis demonstrated that gender (P = 0.0136), UICC stage (P = 0.002), p53 expression (P - 0.0002) and Bcl-2 expression (P = 0.0243) were independent factors predictive of recurrence. The proportional hazards model identified p53 (P = 0.0009), UICC stage (P = 0.0480), Sender (P 0.0049), but not Bcl-2 (P = 0.1503), as independently related to disease-free survival. Looking at the p53/Bcl-2 subgroups, the poorest prognosis was observed in the p53+/Bcl-2- subgroup, whereas patients whose tumours were p53-/Bcl-2 + had the best prognosis (P < 0.0001). Immunohistochemical assessment of both p53 and Bcl-2 status may. be valuable in predicting recurrence and survival after curative surgery for rectal cancer. Therefore, they play a role as prognostic factors in rectal cancer. p53 is a stronger predictor of prognosis than Bcl-2. (C) 2000 Else Elsevier Science Ltd. All rights reserved.