Patients who have inoperable lung cancer usually undergo chemotherapy and have problems such as a resistance against chemotherapeutic agents during the treatment. Glutathione S-transferase (GST) is one of the detoxication-related enzymes. We studied the relationship between immunohisto-chemical staining of GST-pi type and cisplatin + etoposide chemotherapy in patients with untreated primary non-small cell lung cancer (NSCLC). Of patients diagnosed as having primary lung cancer, 60 cases (49 men, 11 women; median age, 75.2 years, 35 squamous cell carcinomas and 25 adenocarcinomas) with stage, which were not surgically treatable, were examined immunohistochemically by using anti-GST-pi antibody. Chemotherapy (cisplatin 100 mg/m(2) i.v. day 1, etoposide 100 mg/m(2) i.v. days 1-3) was administered for all 60 patients and was repeated at 28 days for two cycles. After two courses of treatment, the therapeutic response was evaluated. Of 60 cases, 36 (60%) were GST-pi positive and 24 (40%) negative at pretreatment. In 24 patients with GST-pi negative expression, the chemo-therapeutic response rate was 66.7% (16/24), while the response rate was 25% (9/36) in the 36 GST-pi positive patients. The mRNA levels of GST-pi were similar to the immunohistochemical expressions in some of these cases by using reverse transcription-polymerase chain reaction analysis. The results suggest that GST-pi: expression in cancer tissues is related to response to cisplatin + etoposide chemotherapy in untreated primary NSCLC patients, and may be useful as a predictor of chemotherapy response.

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