Relationship of P-glycoprotein and carcinoembryonic antigen expression in human colon carcinoma to local invasion, DNA ploidy, and disease relapse.

Abstract

The clinical significance of expression of the MDR1 gene product P-glycoprotein (P-gp) in relation to the intrinsic drug resistance and progression of human colon cancer is largely unknown. To elucidate the role of P-gp in these cancers further, the frequency and intensity of P-gp and carcinoembryonic antigen (CEA) immunostaining were measured at the single-cell level and correlated with known prognostic indices (i.e., DNA ploidy, vessel/lymphatic microinvasion, histologic grade, and disease relapse). Fifty-two untreated Dukes' Stage B2 colon cancers were immunostained with the anti-P-gp monoclonal antibodies JSB-1 and HYB-241, and anti-CEA. DNA content and cell proliferation were measured by flow cytometry. JSB-1 and HYB-241 detected P-gp in 44 and 42 of 52 carcinomas, respectively, and CEA was found in 50 of the 52 tumors. The level of P-gp expression was not associated with DNA ploidy, indices of local invasiveness, or histologic grade. In a multivariate analysis, however, a high level of P-gp expression (as assessed by JSB-1), DNA aneuploidy, microinvasion, and single carcinoma cell invasion individually predicted disease relapse (P < 0.05). The results indicate that diffuse P-gp immunostaining is present in the majority of Stage B2 human colon cancers and therefore may be an important contributor to their intrinsic drug resistance. The association between a high level of P-gp expression and disease relapse suggests that P-gp can be of prognostic value in Stage B2 colon cancers.