63PNrf2 expression in surgically resected lung adenocarcinomas: Its association with clinicopathologic features and driver oncogene alterations

• Published in: Annals of oncology Vol. 30; no. Supplement_7
• Main Authors: Takamochi, K, Hayashi, T, Hara, K, Mitsuishi, Y, Takahashi, F, Suehara, Y, Suzuki, K
• Format: Journal Article
• Language: English
• Published: Oxford University Press 01.11.2019
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdz413.067

Abstract Background Nrf2 is a transcription factor associated with cancer growth and chemotherapy resistance. Nrf2 expression levels may be associated with prognosis of lung cancer, but previous results have been inconsistent. Methods The expression of Nrf2 in 1037 surgically resected lung adenocarcinoma (LAD) specimens was evaluated by immunohistochemistry. Nrf2 positivity was defined based on the intensity of stained nucleus of tumor cells on the tissue microarray: negative, weakly positive and strongly positive. The correlations between the Nrf2 expression and the prognosis, clinicopathological features and driver oncogene alterations were analyzed. Results The Nrf2 expression was negative in 236 (23%) of 1037 tumors, weakly positive in 444 (43%) and strongly positive in 357 (34%). The proportion of Nrf2-positive tumors was significantly higher in patients with pathological stage I (81%), tumors with EGFR mutations (87%) or KRAS mutations (87%), tumors without ALK fusions (78%) or ROS1 fusions (78%). The Nrf2 expression was not associated with the age, gender and smoking status. In multivariate analysis (Logistic regression model), pathological stage I, positive EGFR or KRAS mutation status were significant predictors of Nrf2 positivity. The increased expression of Nrf2 was associated with longer overall survival regardless of driver oncogene status. In multivariate analysis (Cox proportional hazards model), advanced age, male gender, advanced pathological stage and negative EGFR mutation status were significant unfavorable prognostic factors. Conclusions LADs that positively express Nrf2 have unique clinicopathological features. The increased expression of Nrf2 is a favorable prognostic marker in surgically resected LAD. Legal entity responsible for the study The authors. Funding AMED. Disclosure All authors have declared no conflicts of interest.