MDR Proteins Expression in AIDS-Related Non-Hodgkin’s Lymphoma.

Multidrug resistance (MDR) to chemotherapeutic drugs is a major obstacle in the treatment of patients with cancer. One of the best characterized resistance mechanisms of resistance in tumors cells is the MDR mediated by P-glycoprotein (Pgp) and multidrug resistant related protein (MRP). MDR expression in non-Hodgkin lymphoma (NHL) range widely being dependent on factors as the different antibodies, detection methods used, and clinical status (untreated patients or after failure of chemotherapy). AIDS-related NHL is associated with high rate of relapse and short overall median survivals. Previous study demonstrated that MDR positive AIDS-related LNH patients had a lower complete remission compared with MDR negative patients. In this study we analysed expression of Pgp and MRP by immunohistochemistry (IHC) in 62 high grade B-cell types NHL in an attempt to determine if MDR expression is dependent on previous anti-HIV therapy, a group of drugs well-known substrates for MDR expression. IHC detection of Pgp and MRP was performed using monoclonal antibodies according avidin-biotin method. Expression of Pgp was observed in 30 of 62 (48.4%) cases of AIDS-related NHL. MRP expression was examined in 27 specimens being 7 cases considered positives (25.9%). Co-expression of Pgp and MRP was detected in 5 out of 27 (18.5%) samples, whose patients had not previous NHL diagnosis. Anti-HIV therapy was used in 31/62 patients prior NHL diagnosis. Sixteen out of 30 patients that exhibited positive Pgp cells had not received anti-HIV therapy before NHL. Our study shows that expression of Pgp did not correlate to previous anti-HIV therapy and can be also observed in newly diagnosed AIDS-related NHL. The biological linkages between NHL and MDR phenotype are not fully understood. However, our results showed an intrinsic resistance in these patients indicating that the MDR modulation during chemotherapy could be a new approach for treatment in AIDS-related NHL.