MDR-1 EXPRESSION IN NON-HODGKINS-LYMPHOMAS IS UNRELATED TO TREATMENT INTENSITY OR RESPONSE TO THERAPY

Over-expression of the MDR-1 gene, which codes for P-glycoprotein, is thought to be an important mechanism in the drug resistance exhibited by many tumours. A number of chemotherapeutic agents which induce MDR- 1 expression are also components of combination chemotherapies that ar e used in the treatment of high grade non-Hodgkin's lymphomas (NHL). W e have therefore examined expression of MDR-1 in a series of NHL by No rthern blot analysis as well as investigated the localization of P-gly coprotein by immunohistochemistry. The series included 11 hyperplastic reactive nodes and tonsils, 17 low grade NHL and 15 high grade NHL. T he levels of MDR-1 mRNA were quantified by scanning densitometry and c omparison with levels of glucose-6-phosphate dehydrogenase (G6PD). The MDR-1 mRNA was observed in both non-malignant and NHL tissues. Immuno histochemical staining revealed that expression of MDR-1 mRNA in react ive nodes was related to the presence of P-glycoprotein in lymphocytes , however, P-glycoprotein was apparent in both the reactive lymphocyte s and tumour cells in the NHL samples. Elevated mRNA levels (2-3 fold increase) were observed in some low grade and high grade NHL relative to those observed in reactive lymphoid tissue. There appeared to be li ttle correlation, however, between expression of the MDR-1 gene and ei ther treatment intensity or response to therapy. The drug resistance t hat is often encountered in NHL patients is therefore likely to involv e mechanisms other than over-expression of P-glycoprotein.