Effects of MDR1/P-glycoprotein expression on prognosis in advanced colorectal cancer after surgery

Resistance to chemotherapeutic agents is a major problem for successful cancer treatment. P-glycoprotein (Pgp), a product of the multidrug resistance (MDR)1 gene expressed in cancer cells, is one of the mechanism of MDR. However, there are few reports regarding the effects of Pgp on prognosis of colorectal cancer (CRC) after surgery. We examined a total of 80 patients (45 males and 35 females with an average age of 69 years) whose CRCs were classified into stage 2-4 and completely resected surgically in our institute between January 1990 and September 1999. To evaluate Pgp expression in CRC, immunohistochemical stain was performed with a monoclonal antibody. Relationships between Pgp expression and clinicopathological variables which may have affected prognosis were evaluated. Survival curves were calculated using the Kaplan-Meier method, and differences were evaluated with the log-rank test. The Cox's proportional hazards model was used in the univariate and multivariate survival analysis. Pgp expression showed a significant correlation with histological differentiation (p=0.023). However, no correlation was observed with gender, tumor location, lymph node metastasis, lymphatic invasion, venous invasion, and cancer stages. Survival rates after surgery tended (p=0.093) to be higher in Pgp (+) than Pgp (-) patients. Pgp was not a significant prognostic factor by univariate analysis and multivariate analysis adjusted for other clinicopathologic variables. Survival rates after surgery tended to be higher in Pgp (+) than Pgp (-) patients and Pgp expression was correlated with histological differentiation of CRC. Thus, a relative resistance of CRC to conventional chemotherapy may be partly caused by Pgp expressed in well or moderately differentiated CRC. However, Pgp expression was not a significant independent prognostic factor in advanced CRC after surgery.