PURPOSE: The importance of biomarker analysis in patients with lung cancer is well known and we have previously reported the usefulness of endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) for biomarker assessment as well as pathological diagnosis. The purpose of this study was to analyze the multiple gene mutation status in samples obtained by EBUS-TBNA and to examine the correlation between treatments and outcomes.
METHODS: 156 patients with primary non-small cell lung cancer (NSCLC) diagnosed as metastatic carcinoma by EBUS-TBNA of hilar and/or mediastinal lymph nodes were enrolled. We evaluated the gene mutation status of EGFR, K-ras and p53. In addition, retrospective chart review was performed. EGFR gene was analyzed using PNA-LNA PCR clamp method (n=156). K-ras (exon 2-3) and p53 (exon 4-8) were analyzed by direct sequence (n=113).
RESULTS: There were 115 male and 41 female with median age of 64.3 years (36-90). These patients included 127 adenocarcinoma, 21 squamous cell carcinoma and 8 other NSCLC histology. EGFR gene mutation was detected in 42 cases (26.9%). 23 cases with EGFR mutation and 5 cases without mutation were administered EGFR-tyrosine kinase inhibitors (EGFR-TKIs). All 23 cases with mutation received Gefitinib with overall response rate (PR) of 54.5% and disease control rate (PR+SD) of 86.4% (RECIST). Out of the 5 cases without mutation, 2 cases were treated by Gefitinib resulting in PD and 2 cases were treated by Elrotinib resulting in PR+SD. K-ras gene mutation was detected only in 4 cases (3.5%) and these cases did not receive EGFR-TKIs. p53 gene mutation was detected in 47 cases (41.6%). Cases with p53 gene mutation showed relatively poor prognosis after any kind of chemotherapy (p=0.1391).
CONCLUSION: Multi-gene mutation analysis can be performed in EBUS-TBNA samples obtained from metastatic lymph nodes in lung cancer patients.
CLINICAL IMPLICATIONS: EBUS-TBNA allows genetic evaluations of tumor cells within the lymph node which may allow clinicians to select treatments especially in EGFR-TKIs.
DISCLOSURE: Takahiro Nakajima, Grant monies (from sources other than industry) This research was supported, in part, by the Ministry of Education, Culture, Sports, Science and Technology, Grant-in-Aid for Young Scientists (B) No. 21791340 in 2009 (TN) and Grant-in-Aid for Cancer Research from Ministry of Health, Labor and Welfare in 2009 (TN).; Grant monies (from industry related sources) Kazuhiro Yasufuku has received unrestricted grant from Olympus Medical Corporation for Continuing Medical Education.; Other Takahiro Nakajima received Research Fellowship from The Uehara Memorial Foundation for the research in overseas.; No Product/Research Disclosure Information