P53 AND PCNA EXPRESSION IN ADVANCED COLORECTAL-CANCER - RESPONSE TO CHEMOTHERAPY AND LONG-TERM PROGNOSIS

In a series of 71 patients with advanced colorectal cancer treated wit h biochemically modulated 5-fluorouracil (5-FU) and methotrexate (MTX) , we investigated the relationship between the proliferating-cell nucl ear antigen (PCNA) (PC10) and p53 (Pab 1801) primary-tumor immunohisto chemical expression with respect to clinical response and long-term pr ognosis, Nuclear p53 expression was demonstrated in 44% of samples (an y number of positive tumor cells) while all tumors showed a certain de gree of PCNA immunostaining. PCNA immunostaining was correlated with h istopathologic grade and p53 expression, while p53 was not correlated with any of the parameters considered. The probability of clinical res ponse to biochemically modulated 5-FU was independent of p53 and PCNA expression. p53 expression (all cut-off values) was not associated wit h short- or long-term clinical prognosis, whereas patients with higher PCNA primary-tumor expression showed longer survival from treatment a nd survival from diagnosis, according to univariate and multivariate a nalysis, particularly in the sub-set of colon-cancer patients. We conc lude that the clinical response of advanced-colorectal-cancer patients to biochemically modulated 5-FU and MTX cannot be predicted by PCNA a nd p53 primary-tumor expression, but high PCNA expression appears to b e independently related to long-term prognosis. (C) 1996 Wiley-Liss, I nc.