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

Frank A Sinicrope, J. Hart, T. A. Brasitus, F. Michelassi, J. J. Lee, A. R. Safa

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2908-2917
Number of pages10
JournalCancer
Volume74
Issue number11
DOIs
StatePublished - 1994
Externally publishedYes

Keywords

  • carcinoembryonic antigen
  • colon cancer
  • DNA ploidy
  • P-glycoprotein
  • prognosis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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