• Sarah Park, Alison J Holmes-Tisch, Eun Yoon Cho, Young Mog Shim, Jinkook Kim, Hyo Song Kim, Jeeyun Lee, Yeon Hee Park, Jin Seok Ahn, Keunchil Park, Pasi A Jänne, and Myung-Ju Ahn.
• Department of Medicine, Division of Hematology-Oncology, Hangang Sacred Heart Hospital, Hallym University School of Medicine, Seoul, Korea.
• J Thorac Oncol. 2009 Jul 1;4(7):809-15.

IntroductionFor the identification of the patients who most likely benefit from epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC), molecular assays are considered to be of paramount importance. Given the heterogeneity of NSCLC at the molecular level, this study was conducted to determine the discrepancy in EGFR mutations between primary tumors and the corresponding lymph node metastasis.Patients And MethodsSurgically resected 101 paired primary NSCLC and metastatic lymph nodes were evaluated for the EGFR mutations by direct DNA sequencing and heteroduplex analysis.ResultsEGFR mutation was detected in 29.7% (30 of 101) of the primary tumors and in 27.7% of lymph node metastases (28 of 101) by either direct sequencing or heteroduplex analysis, respectively. By direct sequencing, 12 cases (11.9%) showed discordance in EGFR mutations between primary tumors and metastasis. In 11 cases, EGFR mutations were detected only in the primary tumor, whereas 1 case only in lymph node metastases. By heteroduplex analysis, 17 cases (16.8%) were discordant. Ten cases were primary tumor positive and lymph node negative, whereas seven cases were lymph node positive and primary tumor negative.ConclusionsA considerable proportion of NSCLC showed discrepancy in EGFR mutations between primary tumors and metastatic lymph nodes, suggesting tumor heterogeneity at the molecular level during the process of metastasis.

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