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

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

Research output: Contribution to journalArticle

47 Citations (Scopus)

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

Fingerprint

Ploidies
Carcinoembryonic Antigen
P-Glycoprotein
Colon
Carcinoma
Recurrence
DNA
Colonic Neoplasms
Drug Resistance
Lymphatic Vessels
Aneuploidy
Neoplasms
Flow Cytometry
Multivariate Analysis
Monoclonal Antibodies
Cell Proliferation
Gene Expression

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Relationship of P-glycoprotein and carcinoembryonic antigen expression in human colon carcinoma to local invasion, DNA ploidy, and disease relapse. / Sinicrope, F. A.; Hart, J.; Brasitus, T. A.; Michelassi, F.; Lee, J. J.; Safa, Ahmad.

In: Cancer, Vol. 74, No. 11, 1994, p. 2908-2917.

Research output: Contribution to journalArticle

Sinicrope, F. A. ; Hart, J. ; Brasitus, T. A. ; Michelassi, F. ; Lee, J. J. ; Safa, Ahmad. / Relationship of P-glycoprotein and carcinoembryonic antigen expression in human colon carcinoma to local invasion, DNA ploidy, and disease relapse. In: Cancer. 1994 ; Vol. 74, No. 11. pp. 2908-2917.
@article{087fd031d0e14d40a878c5f67a04bab9,
title = "Relationship of P-glycoprotein and carcinoembryonic antigen expression in human colon carcinoma to local invasion, DNA ploidy, and disease relapse",
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.",
keywords = "carcinoembryonic antigen, colon cancer, DNA ploidy, P-glycoprotein, prognosis",
author = "Sinicrope, {F. A.} and J. Hart and Brasitus, {T. A.} and F. Michelassi and Lee, {J. J.} and Ahmad Safa",
year = "1994",
doi = "10.1002/1097-0142(19941201)74:11<2908::AID-CNCR2820741104>3.0.CO;2-M",
language = "English (US)",
volume = "74",
pages = "2908--2917",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "11",

}

TY - JOUR

T1 - Relationship of P-glycoprotein and carcinoembryonic antigen expression in human colon carcinoma to local invasion, DNA ploidy, and disease relapse

AU - Sinicrope, F. A.

AU - Hart, J.

AU - Brasitus, T. A.

AU - Michelassi, F.

AU - Lee, J. J.

AU - Safa, Ahmad

PY - 1994

Y1 - 1994

N2 - 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.

AB - 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.

KW - carcinoembryonic antigen

KW - colon cancer

KW - DNA ploidy

KW - P-glycoprotein

KW - prognosis

UR - http://www.scopus.com/inward/record.url?scp=0028081759&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028081759&partnerID=8YFLogxK

U2 - 10.1002/1097-0142(19941201)74:11<2908::AID-CNCR2820741104>3.0.CO;2-M

DO - 10.1002/1097-0142(19941201)74:11<2908::AID-CNCR2820741104>3.0.CO;2-M

M3 - Article

C2 - 7954255

AN - SCOPUS:0028081759

VL - 74

SP - 2908

EP - 2917

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 11

ER -