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 in 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 patients with NSCLC was measured by a sandwich enzyme-linked immunosorbent assay, and the serum concentrations of carcinoembryonic antigen (CEA), squamous cell carcinoma (SCC) antigen, and neuron-specific enolase (NSE) were also examined. Serum levels of these tumor markers were also evaluated in relation to therapeutic response in 69 patients who received combination chemotherapy with platinum compound. Results. Fifty of 121 patients with NSCLC (41.3%) showed elevated serum GST-pi levels above 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 with NSCLC was higher than those of CEA (37.2%), SCC (15.7%), and NSE (14.9%). The mean pretreatment GST-pi level was significantly lower in patients 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 serum GST-pi concentration below the cutoff level (P < 0.02). Neither CEA, SCC, nor NSE showed such a relationship. Conclusions. The serum GST-pi level may have limited value as a tumor marker for NSCLC. Interestingly, pretreatment serum GST-pi levels may be a useful parameter for predicting therapeutic response to combination chemotherapy regimens that include platinum compound.