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 MDR1 gene p roduct P-glycoprotein (P-gp) in relation to the intrinsic drug resista nce and progression of human colon cancer is largely unknown. To eluci date the role of P-gp in these cancers further, the frequency and inte nsity of P-gp and carcinoembryonic antigen (CEA) immunostaining were m easured 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 ant ibodies JSB-1 and HYB-241, and anti-CEA. DNA content and cell prolifer ation were measured by flow cytometry. Results. JSB-1 and HYB-241 dete cted P-gp in 44 and 42 of 52 carcinomas, respectively, and CEA was fou nd in 50 of the 52 tumors. The level of P-gp expression was not associ ated with DNA ploidy, indices of local invasiveness, or histologic gra de. In a multivariate analysis, however, a high level of P-gp expressi on (as assessed by JSB-1), DNA aneuploidy, microinvasion, and single c arcinoma cell invasion individually predicted disease relapse (P < 0.0 5). Conclusions. The results indicate that diffuse P-gp immunostaining is present in the majority of Stage B2 human colon cancers and theref ore 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 colo n cancers.