SESSION TYPE: Biomarkers, Oncogenes and Enhanced Bronchoscopy in NSCLC
PRESENTED ON: Wednesday, October 24, 2012 at 02:45 PM - 04:15 PM
PURPOSE: Surgery with curative intent is the standard treatment of choice for patients with stage I non-small-cell lung cancer (NSCLC). However, even after curative resection of stage I NSCLC, a significant fraction of patients develops recurrent disease. Molecular biomarkers that can predict the risk of recurrence thus need to be identified to improve clinical outcomes. Promoter methylation in various genes has been demonstrated to be involved in the development and/or progression of lung cancer, and has thus been used as a molecular biomarker to accurately predict the outcome of disease.
METHODS: Using the methylation-specific polymerase chain reaction (PCR) assay, promoter methylation of the breast cancer susceptibility gene 1 (BRCA1) was assessed in cancer tissues from 70 patients with curatively resected stage I NSCLC. We evaluated the clinical relevance of BRCA1 methylation status to the outcome of the disease.
RESULTS: Methylation of the BRCA1 promoter was detected in 13 of 70 patients (18.6%). There was no statistically significant relationship between BRCA1 methylation status and any of the clinocopathological features. Univariate analysis showed that degree of differentiation, vessel infiltration, and BRCA1 methylation status were statistically significant as predictors for recurrence (p = 0.0347, p = 0.0300, and p = 0.0369, respectively). Multiple logistic regression analysis revealed that BRCA1 methylation was an independent risk factor for recurrence (p = 0.0197) and that patients with BRCA1 methylation demonstrated significantly poorer recurrence-free survival compared to those without (p = 0.0139). Cox’s proportional hazard regression analysis revealed that BRCA1 methylation was an independent risk factor for recurrence-free survival (p = 0.0155).
CONCLUSIONS: Methylated BRCA1 can be a potential biomarker that predicts the prognosis after curative resection of stage I NSCLC.
CLINICAL IMPLICATIONS: Considering that BRCA1 plays a role in chemotherapy-induced apoptosis, it is plausible that identification of methylated BRCA1 could provide information clinically relevant to tailored adjuvant therapy.
DISCLOSURE: The following authors have nothing to disclose: Hiroaki Harada, Kazuaki Miyamoto, Yoshinori Yamashita, Kikuo Nakano, Kiyomi Taniyama, Yoshihiro Miyata, Morihito Okada
No Product/Research Disclosure InformationDepartment of Respiratory Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure, Japan