Expression of the glutathione-S-transferase π (GST-π) protein correlates with survival in patients with stage I non-small cell lung cancer (NSCLC)

21065 Background: It is important to identify prognostic markers in stage I NSCLC given the 30%-40% risk of recurrence and death despite resection. The role of platinum-based adjuvant chemotherapy remains unclear in stage I NSCLC. The glutathione pathway prevents cellular DNA damage by oxygen free radicals and cytotoxic compounds. GST-p catalyzes conjugation of glutathione to cytotoxic agents and high expression may predict for platinum resistance. The role of GST-p as a prognostic factor in early stage lung cancer is not well evaluated. Methods: In a retrospective cohort of 93 patients with resected stage I NSCLC we used immunohistochemistry (IHC) to study the association of GST-p expression with risk of tumor recurrence and death. None of the patients received adjuvant therapy. IHC was quantified by a visual grading intensity of cytoplasm staining (0= no immunoreactivity; 1=weak; 2= clear reactivity in >50% cancer cells and 3= strong immunoreactivity). Grades 2 and 3 were classified as high and grades 0 and 1 as low GST-p respectively. Results: The mean age of the patients was 67 years. Of the 93 patients, there were 45 (48%) men, 71 (76%) had adenocarcinoma and 66 (71%) had stage IA disease. The median follow-up time was 5.4 years. High GST-p expression was noted in 40 (43%) and 53 had low GST expression. The overall survival at 5 years was 67% with 31 deaths. Patients with high GST expression had a higher overall survival at 5 years- 32/40 (75%) vs. 30/53 (57%) in the low GST group (p=0.018). There was no significant difference in terms of tumor recurrence or recurrence free survival. After adjusting for age, gender, histology, and T stage, patients with low GST-p expression remained at an increased risk of death with a hazard ratio of 2.86 (1.16–7.61, p= 0.015). Conclusions: In this cohort, high expression of GST-p served as an independent prognostic factor in resected stage I NSCLC. These early findings with GST-p are similar to those from the IALT trial wherein the high expression of ERCC1 was associated with chemoresistance but conferred a survival advantage in the absence of chemotherapy (Olaussen, NEJM 2006). These findings merit evaluation in larger prospective series given the small, exploratory and retrospective design of the present study. No significant financial relationships to disclose.