Relationship of the expression of the multidrug resistance gene product (P-glycoprotein) in human colon carcinoma to local tumor aggressiveness and lymph node metastasis

Ronald S Weinstein, Shriram M. Jakate, Jose M. Dominguez, Miriam D. Lebovitz, George K. Koukoulis, Jerome R. Kuszak, Larry F. Klusens, Thomas M. Grogan, Theodore J. Saclarides, Igor B. Roninson, John S. Coon

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Abstract

P-glycoprotein mediates classic multidrug resistance by functioning as an efflux pump that excretes lipophilic chemotherapeutic drugs from cancer cells. We now report an association of P-glycoprotein in colon carcinomas with another tumor property, i.e., enhancement of local tumor aggressiveness. P-glycoprotein was detected with monoclonal antibody immunohistochemistry in 65 of 95 primary colon adenocarcinomas, which were stage B1 or greater. In all but 1 of the 95 cases, solitary invading carcinoma cells were present at the leading edge of the tumor. This subpopulation of invasive carcinoma cells expressed P-glycoprotein (P-Gp+) in 47 of the 95 surgically resected colon specimens. Cases were grouped on the basis of the presence (Group 1, 47 cases) or absence (Group 2, 48 cases) of P-Gp+ invasive carcinoma cells. There was a significantly greater incidence of vessel invasion (P < 0.001) and lymph node metastases (P < 0.01) in Group 1 cases. Groups 1 and 2 did not differ with respect to tumor size, depth of invasion of the bowel wall, histological grade, maximum tumor size, mitotic index, mucin production, or presence of perineural invasion (P > 0.1). Our findings indicate that P-Gp+ invasive colon cancer cells may have an increased potential for dissemination, suggesting that P-glycoprotein may influence cell behavior.

Original languageEnglish (US)
Pages (from-to)2720-2726
Number of pages7
JournalCancer Research
Volume51
Issue number10
StatePublished - May 15 1991

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MDR Genes
P-Glycoprotein
Colon
Lymph Nodes
Neoplasm Metastasis
Carcinoma
Neoplasms
Multiple Drug Resistance
Colonic Neoplasms
Adenocarcinoma
Immunohistochemistry
Monoclonal Antibodies
Incidence
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Relationship of the expression of the multidrug resistance gene product (P-glycoprotein) in human colon carcinoma to local tumor aggressiveness and lymph node metastasis. / Weinstein, Ronald S; Jakate, Shriram M.; Dominguez, Jose M.; Lebovitz, Miriam D.; Koukoulis, George K.; Kuszak, Jerome R.; Klusens, Larry F.; Grogan, Thomas M.; Saclarides, Theodore J.; Roninson, Igor B.; Coon, John S.

In: Cancer Research, Vol. 51, No. 10, 15.05.1991, p. 2720-2726.

Research output: Contribution to journalArticle

Weinstein, RS, Jakate, SM, Dominguez, JM, Lebovitz, MD, Koukoulis, GK, Kuszak, JR, Klusens, LF, Grogan, TM, Saclarides, TJ, Roninson, IB & Coon, JS 1991, 'Relationship of the expression of the multidrug resistance gene product (P-glycoprotein) in human colon carcinoma to local tumor aggressiveness and lymph node metastasis', Cancer Research, vol. 51, no. 10, pp. 2720-2726.
Weinstein, Ronald S ; Jakate, Shriram M. ; Dominguez, Jose M. ; Lebovitz, Miriam D. ; Koukoulis, George K. ; Kuszak, Jerome R. ; Klusens, Larry F. ; Grogan, Thomas M. ; Saclarides, Theodore J. ; Roninson, Igor B. ; Coon, John S. / Relationship of the expression of the multidrug resistance gene product (P-glycoprotein) in human colon carcinoma to local tumor aggressiveness and lymph node metastasis. In: Cancer Research. 1991 ; Vol. 51, No. 10. pp. 2720-2726.
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abstract = "P-glycoprotein mediates classic multidrug resistance by functioning as an efflux pump that excretes lipophilic chemotherapeutic drugs from cancer cells. We now report an association of P-glycoprotein in colon carcinomas with another tumor property, i.e., enhancement of local tumor aggressiveness. P-glycoprotein was detected with monoclonal antibody immunohistochemistry in 65 of 95 primary colon adenocarcinomas, which were stage B1 or greater. In all but 1 of the 95 cases, solitary invading carcinoma cells were present at the leading edge of the tumor. This subpopulation of invasive carcinoma cells expressed P-glycoprotein (P-Gp+) in 47 of the 95 surgically resected colon specimens. Cases were grouped on the basis of the presence (Group 1, 47 cases) or absence (Group 2, 48 cases) of P-Gp+ invasive carcinoma cells. There was a significantly greater incidence of vessel invasion (P < 0.001) and lymph node metastases (P < 0.01) in Group 1 cases. Groups 1 and 2 did not differ with respect to tumor size, depth of invasion of the bowel wall, histological grade, maximum tumor size, mitotic index, mucin production, or presence of perineural invasion (P > 0.1). Our findings indicate that P-Gp+ invasive colon cancer cells may have an increased potential for dissemination, suggesting that P-glycoprotein may influence cell behavior.",
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