Use of Epidermal Growth Factor Receptor/Kirsten Rat Sarcoma 2 Viral Oncogene Homolog Mutation Testing to Define Clonal Relationships Among Multiple Lung Adenocarcinomas: Comparison With Clinical Guidelines

摘要

Background: The incidence of multiple lung adenocarcinomas is rising, making it diffi cult to ndetermine the stage and assign treatment in an increasing number of patients following surgery. nClinical guidelines have been developed to distinguish independent non-small cell lung cancers nfrom metastases, that is, criteria developed by Martini and Melamed and the American College nof Chest Physicians (ACCP). However, these guidelines can be diffi cult to apply and may give nconfl icting results. Here, we report on seven patients in whom epidermal growth factor receptor n( EGFR ) and Kirsten-rat sarcoma 2 viral oncogene homolog ( KRAS ) tumor mutation status was nused to determine clonal relationships among multiple lung lesions. n Methods: We identifi ed seven patients whose paired lung adenocarcinomas were found to harbor ndistinct EGFR or KRAS mutations. We assessed these patients’ disease status using established nclinical guidelines. We also explored the use of comprehensive histologic subtyping (CHS) of tumor nsections to distinguish multiple primaries. n Results: According to the Martini-Melamed criteria, six of the seven patients had multiple pri-nmary lung tumors. By ACCP criteria, three patients had multiple primaries, and three patients nhad metastases. Classifi cation of the seventh patient by ACCP criteria was indeterminate. Muta-ntional testing suggested that all paired tumors were multiple primary adenocarcinomas, which nwas consistent with results from CHS. n Conclusions: Assuming that independent tumor clones harbor distinct mutations, these seven ncases highlight discrepancies between the existing clinical criteria used to distinguish indepen-ndent tumor foci from metastases. EGFR/KRAS mutation testing of multiple lung adenocarcinomas ncan assist in differentiating multiple primary lung adenocarcinomas from metastatic lesions. Use nof CHS in this setting should also be further explored. ncancer.