Expression of P-glycoprotein and glutathione-S-transferase in recurrent lymphomas: the possible role of Epstein-Barr virus, immunophenotypes, and other predisposing factors.

Abstract

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. 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 pi (GST-pi) was determined by an immunohistochemistry method. Expression of mdr-1 or GST-pi was found in 11 (48%) and 12 (52%) cases, respectively. Most (11 of 12) of the GST-pi 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 express 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-pi in their recurrent tumor tissues. (1) mdr-1 expression is a significant prognostic factor in recurrent lymphomas; (2) high expression of mdr-1 is observed in recurrent EBV-associated PTCL; and (3) GST-pi 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-pi in recurrent lymphomas are well worth further exploration.