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Immunohistochemical Identification of P-Glycoprotein in Previously Untreated, Diffuse Large Cell and Immunoblastic Lymphomas¹

Laboratory Service [G. A. N.] and Hematology/Oncology Section [R. T. P.], Minneapolis Veterans Affairs Medical Center, Minneapolis, Minnesota 55417; Department of Laboratory Medicine and Pathology, University of Minnesota Hospital and Clinic, Minneapolis, Minnesota 55455 [W. J., K. G-P.]; Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York 14263 [V. B., C. D. B.]; Laboratory of Anatomic Pathology, Barnes Hospital, Washington University School of Medicine, St. Louis, Missouri 63110 [M. R. W.]; and Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan [T. T.]

Expression of P-glycoprotein has been linked to multidrug resistance in cancer cell lines and human tumors. We investigated the frequency and clinical significance of P-glycoprotein immunoreactivity in 57 previously untreated diffuse large cell and immunoblastic lymphomas. Banked frozen tissue, which had been obtained prior to chemotherapy, was tested for reactivity with 2 monoclonal antibodies (MRK16 and C219) that recognize different domains of P-glycoprotein, using an immunoperoxidase technique. Thirteen of 57 lymphomas (23%) showed strong staining of >50% of neoplastic cells; 15 of 57 (26%) showed labeling of a minority (11–50%) of neoplastic lymphocytes; 14 of 57 (25%) yielded equivocal results (reactivity in <10% of cells); and 15 of 57 (26%) were negative for P-glycoprotein. The 2 monoclonal antibodies were comparable in reactivity. Expression of MDR-1 mRNA was determined in 6 cases with sufficient available tissue, and did not correlate well with the percentages of cells reactive for P-glycoprotein by immunohistochemistry. Thirty-nine of our 57 patients completed multiagent chemotherapy. Contrary to our expectations, we found that P-glycoprotein immunoreactivity did not decrease the likelihood of response to induction chemotherapy. Median survival also was not adversely affected.

¹ Supported in part by funds from the Department of Veterans Affairs Merit Review and from the Coleman Leukemia Research Fund.

² To whom requests for reprints should be addressed, at the Minneapolis Veterans Affairs Medical Center, Laboratory Service 113A, 1 Veteran's Drive, Minneapolis, MN 55417.

Received 12/ 5/91. Accepted 4/20/92.

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