VARIABILITY OF GLUTATHIONE-S-TRANSFERASE ISOENZYME PATTERNS IN MATCHED NORMAL AND CANCER HUMAN BREAST-TISSUE

The determination of GST levels in blood has been proposed as a marker of tumour burden in general, whereas level of the P1 isoenzyme has be en identified as a prognostic factor for breast-cancer patients receiv ing no adjuvant chemotherapy. Particular glutathione S-transferase (GS T) isoenzymes differ in their substrate specificity, however, and thei r presence or absence might therefore account for the resistance of tu mours to particular chemotherapeutic drugs, as already established for cultured cell lines. Determination of the GST isoenzyme profile of a cancer tissue could have prognostic value in the selection of treatmen t if the levels of expression/activity show a degree of variation comp arable with that exhibited by actual patient responses. Using reversed -phase h.p.l.c. to quantify affinity-isolated GSTs, we have analysed f ull isoenzyme profiles in the first large sample of matched normal and cancer human tissues (18 breast-cancer patients). In no patients did the tumour tissues express any isoenzymes that were not found in norma l breast tissue. In addition to the GSTs, another enzyme, identified a s enoyl-CoA isomerase, was regularly found in breast tissue cytosol fo llowing elution from a hexyl-glutathione affinity column. In most case s, the average level of GST was substantially elevated in the cancer t issues above the levels in normal breast tissue from the same patient. Furthermore, the relative levels of the isoenzymes were substantially more variable in the cancer samples than in the normal breast tissue, providing a plausible mechanism for the well established variable res ponse to treatment.