Relationship of P‐glycoprotein and carcinoembryonic antigen expression in human colon carcinoma to local invasion, dna ploidy, and disease relapse

Background. The clinical significance of expression of the MDRl 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). Methods. 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 cy‐tometry. Results. 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). Conclusions. 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.