This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Weinstein, R. S. Articles by Coon, J. S. Search for Related Content PubMed PubMed Citation Articles by Weinstein, R. S. Articles by Coon, J. S.

Relationship of the Expression of the Multidrug Resistance Gene Product (P-Glycoprotein) in Human Colon Carcinoma to Local Tumor Aggressiveness and Lymph Node Metastasis¹

Department of Pathology and Arizona Cancer Center, Tucson, Arizona 85724 [R. S. W., M. D. L., T. M. G.], and Departments of Pathology [S. M. J., G. K. K., J. R. K., L. F. K., J. S. C.] and General Surgery [J. M. D., T. J. S.], Rush-Presbyterian St. Luke's Medical Center, and Department of Genetics, University of Illinois at Chicago [I. B. R.], Chicago, Illinois 60612

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.

¹ This research was supported, in part, in Grant CA41183 from the National Cancer Institute, NIH; funds from the Otho S. A. Sprague Memorial Institute of Chicago, IL; and a Drug Resistance grant from the Bristol-Myers Corporation.

² To whom requests for reprints should be addressed, at Department of Pathology, The University of Arizona Health Sciences Center, 1501 N. Campbell Avenue, Tucson, AZ 85724.

Received 10/ 9/90. Accepted 3/ 1/91.

This article has been cited by other articles:

				K. E. Miletti-Gonzalez, S. Chen, N. Muthukumaran, G. N. Saglimbeni, X. Wu, J. Yang, K. Apolito, W. J. Shih, W. N. Hait, and L. Rodriguez-Rodriguez The CD44 Receptor Interacts with P-Glycoprotein to Promote Cell Migration and Invasion in Cancer Cancer Res., August 1, 2005; 65(15): 6660 - 6667. [Abstract] [Full Text] [PDF]

				W.-C. Yen and W. W. Lamph The selective retinoid X receptor agonist bexarotene (LGD1069, Targretin) prevents and overcomes multidrug resistance in advanced breast carcinoma Mol. Cancer Ther., May 1, 2005; 4(5): 824 - 834. [Abstract] [Full Text] [PDF]

				Y. Mochida, K.-i. Taguchi, S. Taniguchi, M. Tsuneyoshi, H. Kuwano, T. Tsuzuki, M. Kuwano, and M. Wada The role of P-glycoprotein in intestinal tumorigenesis: disruption of mdr1a suppresses polyp formation in ApcMin/+ mice Carcinogenesis, July 1, 2003; 24(7): 1219 - 1224. [Abstract] [Full Text] [PDF]

				G-T Ho, F M Moodie, and J Satsangi Multidrug resistance 1 gene (P-glycoprotein 170): an important determinant in gastrointestinal disease? Gut, May 1, 2003; 52(5): 759 - 766. [Abstract] [Full Text]

				U Potocnik, M Ravnik-Glavac, R Golouh, and D Glavac Naturally occurring mutations and functional polymorphisms in multidrug resistance 1 gene: correlation with microsatellite instability and lymphoid infiltration in colorectal cancers J. Med. Genet., May 1, 2002; 39(5): 340 - 346. [Full Text] [PDF]

				D. Conze, L. Weiss, P. S. Regen, A. Bhushan, D. Weaver, P. Johnson, and M. Rincon Autocrine Production of Interleukin 6 Causes Multidrug Resistance in Breast Cancer Cells Cancer Res., December 1, 2001; 61(24): 8851 - 8858. [Abstract] [Full Text] [PDF]

				C. Duhem, F. Ries, and M. Dicato What does Multidrug Resistance (MDR) Expression Mean in the Clinic? Oncologist, June 1, 1996; 1(3): 151 - 158. [Abstract] [Full Text] [PDF]

				R. Mesa-Tejada, J. M. Johnston, S. Duensing, A. Ganser, J. Atzpodien, N. Baldini, and F. Bertoni P-Glycoprotein and Multidrug Resistance N. Engl. J. Med., May 16, 1996; 334(20): 1335 - 1337. [Full Text]

				G. Giaccone and H. M. Pinedo Drug Resistance Oncologist, February 1, 1996; 1(1): 82 - 87. [Abstract] [Full Text] [PDF]

				K. P. Gupta, N. E. Ward, K. R. Gravitt, P. J. Bergman, and C. A. O'Brian Partial Reversal of Multidrug Resistance in Human Breast Cancer Cells by an N-Myristoylated Protein Kinase C-alpha Pseudosubstrate Peptide J. Biol. Chem., January 26, 1996; 271(4): 2102 - 2111. [Abstract] [Full Text] [PDF]

				H. M. Pinedo and G. Giaccone P-Glycoprotein -- A Marker of Cancer-Cell Behavior N. Engl. J. Med., November 23, 1995; 333(21): 1417 - 1419. [Full Text]