Placental isoform glutathione S-transferase and P-glycoprotein expression in advanced nonsmall cell lung cancer: association with response to treatment and survival.

BACKGROUND

Increased expression of the glutathione S-transferase placental isoform (GST-pi) and of P-glycoprotein (P-gp) in tissues from patients with nonsmall cell lung cancer (NSCLC) has been associated with poor antineoplastic drug sensitivity, response to treatment, and survival. However, the diagnosis of advanced NSCLC often is based on cytology. The objectives of the current study were to examine GST-pi and P-gp expression in cytologic specimens from patients with unresectable NSCLC and to determine the association of that expression with response to chemotherapy and survival.

METHODS

Patients with unresectable, cytologically diagnosed NSCLC were eligible for the study. Diagnosis was made by fiberoptic bronchoscopy, and staging was done according to international standards. All patients received sequential chemoradiotherapy and were re-evaluated for treatment response. GST-pi and P-gp expression levels were evaluated by immunocytochemistry and immunohistochemistry of bronchial brushing/washing and bronchial tissue biopsy, respectively. Survival was defined as the time between diagnosis and death or last follow-up at 24 months.

RESULTS

Thirty-nine patients were included in the study. There were 35 men and 4 women, and the mean patient age (+/-standard deviation was 61.4 years (+/-9.1 years). There were 4 patients with stage IIIA NSCLC, 32 patients with stage IIIB NSCLC, and 3 patients with stage IV NSCLC. Cytologic evaluation of GST-pi and P-gp expression paralleled expression determined in pathology specimens. GST-pi and P-gp expression levels were associated inversely with response to chemotherapy and survival.

CONCLUSIONS

Cytologic evaluation of GST-pi and P-gp expression may predictor the response to treatment and the survival of patients with advanced NSCLC.