SERUM GLUTATHIONE-S-TRANSFERASE-PI LEVEL AS A TUMOR-MARKER FOR NONSMALL CELL LUNG-CANCER - POTENTIAL PREDICTIVE VALUE IN CHEMOTHERAPEUTIC RESPONSE

Background. Resistance to chemotherapeutic agents is a major problem i n non-small cell lung cancer (NSCLC) chemotherapy, and recent studies have indicated that glutathione S-transferase-pi (GST-pi) may play an important role in the resistance of cancer cells to alkylating agents that include platinum compound. Methods. GST-pi in serum of 121 patien ts with NSCLC was measured by a sandwich enzyme-linked immunosorbent a ssay, and the serum concentrations of carcinoembryonic antigen (CEA), squamous cell carcinoma (SCC) antigen, and neuron-specific enolase (NS E) were also examined. Serum levels of these tumor markers were also e valuated in relation to therapeutic response in 69 patients who receiv ed combination chemotherapy with platinum compound. Results. Fifty of 121 patients with NSCLC (41.3%) showed elevated serum GST-pi levels ab ove a cutoff value of 34.8 ng/ml (mean + two standard deviations in 30 healthy control subjects). The positive rate of GST-pi in patients wi th NSCLC was higher than those of CEA (37.2%), SCC (15.7%), and NSE (1 4.9%). The mean pretreatment GST-pi level was significantly lower in p atients with a partial response to chemotherapy than in those with no response (26.9 +/- 11.3 ng/ml versus 38.8 +/- 16.7 ng/ml; P < 0.003). Among patients with elevated levels of pretreatment serum GST-pi, only 13.8% (four of 29) responded to the combination chemotherapy, whereas partial response was observed in 40.0% of patients (16 of 40) with se rum GST-pi concentration below the cutoff level (P < 0.02). Neither CE A, SCC, nor NSE showed such a relationship. Conclusions. The serum GST -pi level may have limited value as a tumor marker for NSCLC. Interest ingly, pretreatment serum GST-pi levels may be a useful parameter for predicting therapeutic response to combination chemotherapy regimens t hat include platinum compound.