Mutations in Keap1 Are a Potential Prognostic Factor in Resected Non-small Cell Lung Cancer

Background: Mutations in Kelch-like ECH-associated protein 1 (Keap 1) have been reported to protect tumor cells from chemotherapeutic agents. However, their prognostic significance in nonsmall cell lung cancer (NSCLC) is still unclear. In this study, we examined the effect of Keep! gene mutations on survival and disease-free interval using resected primary NSCLC tissue. Methods: We retrospectively analyzed the tumors from 79 patients with completely resected pathological Stage I-II NSCLC for the presence of Keap1 gene mutations and examined the prognosis of the patients. = Results: Keap1 gene mutations were detected in four patients (5.1%). The postoperative 5-year survival rate for patients with Keap1 mutations was significantly lower than those without a mutation (25% vs. 76%, P = 0.038). The postoperative 5-year disease-free survival rate for patients with a mutant Keap1 tumor was slightly lower than for patients with Keap1 wild-type tumors (25% vs. 66%, P = 0.057). Conclusions: Keap1 gene mutations are likely to be associated with a worse prognosis and lower postoperative disease-free survival rates in pathological Stage I-II NSCLC. J. Surg. Oncol. 2010:101:500-506. (C) 2010 Wiley-Liss, Inc.