EXPRESSION OF P-GLYCOPROTEIN AND GLUTATHIONE-S-TRANSFERASE IN RECURRENT LYMPHOMAS - THE POSSIBLE ROLE OF EPSTEIN-BARR-VIRUS, IMMUNOPHENOTYPES, AND OTHER PREDISPOSING FACTORS

Purpose: We previously have reported the poor prognoses of recurrent peripheral T-cell lymphoma (PTCL) and Epstein-Barr virus (EBV)-associated PTCL (J Clin Oncol 7:725-731, 1989; Blood 77:799-808, 1991). To study the role that drug resistance plays in this scenario, we conducted a retrospective study of 23 adult patients. Patients and Methods: All patients had recurrent lymphoma tissue available for immunophenotyping and screening for the existence of EBV DNA in tumor cells by Southern blot analysis and in situ hybridization. Expression of a multidrug resistance P-glycoprotein ([P-gp]mdr-1) and a glutathione redox cycle-related glutathione-S-transferase π (GST-π) was determined by an immunohistochemistry method. Results: Expression of mdr-1 or GST-π was found in 11 (48%) and 12 (52%) cases, respectively. Most (11 of 12) of the GST-π expression occurred simultaneously with mdr-1. Prechemotherapy tumor tissues were available in 11 cases; only two (18.2%) of these cases expressed mdr-1. Four (36%) of 11 cases that expressed mdr-1 (mdr-1 ( + )) and nine (90%) of 10 cases that did not ex-press mdr-1 (mdr-1( - )) responded to second-line chemotherapy (P < .05). The survival-after-recurrence (SAR) curves significantly favored mdr-1 ( - ) recurrent lymphoma(P < .05). The mdr-1 expression was further correlated with the immunophenotype and EBV association. All six cases of EBV-associated lymphoma (PTCL, five cases; Hodgkin's disease, one case) had significant simultaneous expression of mdr-1 and GST-π in their recurrent tumor tissues. Conclusion: (1) mdr-1 expression is a significant prognostic factor in recurrent lymphomas; (2) high expression of mdr-1 is observed in recurrent EBV-as-sociated PTCL; and (3) GST-π usually expresses simultaneously with mdr-1 in recurrent lymphomas. The role of EBV in the development of mdr-1 and the biologic significance of the simultaneous expression of mdr-1 and GST-T in recurrent lymphomas are well worth further exploration. © 1993 by American Society of Clinical Oncology.