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 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 cytometry.


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.
Sinicrope
F A
FA
Department of Medicine, University of Chicago Cancer Research Center, Illinois.
Hart
J
J
Brasitus
T A
TA
Michelassi
F
F
Lee
J J
JJ
Safa
A R
AR
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D005544:Forecasting; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011003:Ploidies; D011379:Prognosis
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002272:Carcinoembryonic Antigen; D004273:DNA, Neoplasm