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

Resistance to chemotherapeutic agents is a major problem for successful can cer treatment. P-glycoprotein (Pgp), a product of the multidrug resistance (MDR)1 gene expressed in cancer cells, is one of the mechanism of MDR. Howe ver, there are few reports regarding the effects of Pgp on prognosis of col orectal 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 class ified into stage 2-4 and completely resected surgically in our institute be tween January 1990 and September 1999. To evaluate Pgp expression in CRC, i mmunohistochemical stain was performed with a monoclonal antibody. Relation ships between Pgp expression and clinicopathological variables which may ha ve 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 m ultivariate survival analysis. Pgp expression showed a significant correlat ion with histological differentiation (p=0.023). However, no correlation wa s observed with gender, tumor location, lymph node metastasis, lymphatic in vasion, venous invasion, and cancer stages. Survival rates after surgery te nded (p=0.093) to be, higher in Pgp (+) than Pgp (-) patients. Pgp was not a significant prognostic factor by univariate analysis and multivariate ana lysis adjusted for other clinicopathologic variables. Survival rates after surgery tended to be higher in Pgp (+) than Pgp (-) patients and Pgp expres sion was correlated with histological differentiation of CRC. Thus, a relat ive resistance of CRC to conventional chemotherapy may be partly caused by Pgp expressed in well or moderately differentiated CRC. However, Pgp expres sion was not a significant independent prognostic factor in advanced CRC af ter surgery.