PURPOSE: Lung cancer remains to be the leading cause of cancer deaths despite the introduction of various chemotherapeutic agents. It would be ideal if the chemosensitivity can be predicted from biopsy specimens prior to treatment of lung cancer. Several types of aberrant methylation of DNA repair related genes are known to be associated with chemosensitivity. We have reported the usefulness of endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) for lymph node staging of lung cancer. The purpose of this study was to develop and analyze the feasibility of detecting aberrant methylation in samples obtained by EBUS-TBNA and to examine the correlation between multigene aberrant methylation profiling and response to chemotherapy.
METHODS: Thirty patients with primary non-small cell lung cancer diagnosed as metastatic carcinoma in hilar and/or mediastinal lymph node by EBUS-TBNA were enrolled. We evaluated the methylation status of a panel of six genes (FANCF, Reprimo, TMS1/ASC, Activated Protein-2alpha, CHFR, ATM) using methylation-specific PCR. Twenty-four patients with metastatic adenocarcinoma or squamous cell carcinoma received platinum-based combination chemotherapy and were evaluated for their response to chemotherapy following RECIST criteria.
RESULTS: Aberrant methylation was detected as follows: 9 cases of FANCF (30.0%), 14 cases of Reprimo (46.7%), 10 cases of TMS1/ASC (33.3%), 19 cases of Activated Protein-2α (63.3%) and no aberrant methylation was detected for CHFR and ATM. In response to chemotherapy, there were one CR, 6 PR, 12 SD and 5 PD cases. A comparison of the number of methylated genes to chemosensitivity revealed that the number of methylated gene was significantly smaller in the PD group than in the non-PD group (p=0.0435).
CONCLUSION: Aberrant methylation analysis can be performed in EBUS-TBNA samples obtained from metastatic lymph nodes in lung cancer patients. EBUS-TBNA allows genetic evaluations of tumor cells within the lymph node which may allow clinicians to predict chemosensitivity.
CLINICAL IMPLICATIONS: EBUS-TBNA samples provides molecular biological information which will be useful for the treatment of lung cancer. This raises the possibility of “tailored treatment” using the most effective chemotherapeutic agents.
DISCLOSURE: Takahiro Nakajima, No Financial Disclosure Information; No Product/Research Disclosure Information