BACKGROUND: The incidence of multiple lung adenocarcinomas is rising, making it difficult to determine the stage and assign treatment in an increasing number of patients following surgery. Clinical guidelines have been developed to distinguish independent non-small cell lung cancers from metastases, that is, criteria developed by Martini and Melamed and the American College of Chest Physicians (ACCP). However, these guidelines can be difficult to apply and may give conflicting results. Here, we report on seven patients in whom epidermal growth factor receptor (EGFR) and Kirsten-rat sarcoma 2 viral oncogene homolog (KRAS) tumor mutation status was used to determine clonal relationships among multiple lung lesions. METHODS: We identified seven patients whose paired lung adenocarcinomas were found to harbor distinct EGFR or KRAS mutations. We assessed these patients' disease status using established clinical guidelines. We also explored the use of comprehensive histologic subtyping (CHS) of tumor sections to distinguish multiple primaries. RESULTS: According to the Martini-Melamed criteria, six of the seven patients had multiple primary lung tumors. By ACCP criteria, three patients had multiple primaries, and three patients had metastases. Classification of the seventh patient by ACCP criteria was indeterminate. Mutational testing suggested that all paired tumors were multiple primary adenocarcinomas, which was consistent with results from CHS. CONCLUSIONS: Assuming that independent tumor clones harbor distinct mutations, these seven cases highlight discrepancies between the existing clinical criteria used to distinguish independent tumor foci from metastases. EGFR/KRAS mutation testing of multiple lung adenocarcinomas can assist in differentiating multiple primary lung adenocarcinomas from metastatic lesions. Use of CHS in this setting should also be further explored.
BACKGROUND: The incidence of multiple lung adenocarcinomas is rising, making it difficult to determine the stage and assign treatment in an increasing number of patients following surgery. Clinical guidelines have been developed to distinguish independent non-small cell lung cancers from metastases, that is, criteria developed by Martini and Melamed and the American College of Chest Physicians (ACCP). However, these guidelines can be difficult to apply and may give conflicting results. Here, we report on seven patients in whom epidermal growth factor receptor (EGFR) and Kirsten-ratsarcoma 2 viral oncogene homolog (KRAS) tumor mutation status was used to determine clonal relationships among multiple lung lesions. METHODS: We identified seven patients whose paired lung adenocarcinomas were found to harbor distinct EGFR or KRAS mutations. We assessed these patients' disease status using established clinical guidelines. We also explored the use of comprehensive histologic subtyping (CHS) of tumor sections to distinguish multiple primaries. RESULTS: According to the Martini-Melamed criteria, six of the seven patients had multiple primary lung tumors. By ACCP criteria, three patients had multiple primaries, and three patients had metastases. Classification of the seventh patient by ACCP criteria was indeterminate. Mutational testing suggested that all paired tumors were multiple primary adenocarcinomas, which was consistent with results from CHS. CONCLUSIONS: Assuming that independent tumor clones harbor distinct mutations, these seven cases highlight discrepancies between the existing clinical criteria used to distinguish independent tumor foci from metastases. EGFR/KRAS mutation testing of multiple lung adenocarcinomas can assist in differentiating multiple primary lung adenocarcinomas from metastatic lesions. Use of CHS in this setting should also be further explored.
Authors: L V Sequist; R S Heist; A T Shaw; P Fidias; R Rosovsky; J S Temel; I T Lennes; S Digumarthy; B A Waltman; E Bast; S Tammireddy; L Morrissey; A Muzikansky; S B Goldberg; J Gainor; C L Channick; J C Wain; H Gaissert; D M Donahue; A Muniappan; C Wright; H Willers; D J Mathisen; N C Choi; J Baselga; T J Lynch; L W Ellisen; M Mino-Kenudson; M Lanuti; D R Borger; A J Iafrate; J A Engelman; D Dias-Santagata Journal: Ann Oncol Date: 2011-11-09 Impact factor: 32.976
Authors: Andrew G Nicholson; Kathleen Torkko; Patrizia Viola; Edwina Duhig; Kim Geisinger; Alain C Borczuk; Kenzo Hiroshima; Ming S Tsao; Arne Warth; Sylvie Lantuejoul; Prudence A Russell; Erik Thunnissen; Alberto Marchevsky; Mari Mino-Kenudson; Mary Beth Beasley; Johan Botling; Sanja Dacic; Yasushi Yatabe; Masayuki Noguchi; William D Travis; Keith Kerr; Fred R Hirsch; Lucian R Chirieac; Ignacio I Wistuba; Andre Moreira; Jin-Haeng Chung; Teh Ying Chou; Lukas Bubendorf; Gang Chen; Giuseppe Pelosi; Claudia Poleri; Frank C Detterbeck; Wilbur A Franklin Journal: J Thorac Oncol Date: 2017-11-07 Impact factor: 15.609
Authors: Snjezana Dogan; Ronglai Shen; Daphne C Ang; Melissa L Johnson; Sandra P D'Angelo; Paul K Paik; Edyta B Brzostowski; Gregory J Riely; Mark G Kris; Maureen F Zakowski; Marc Ladanyi Journal: Clin Cancer Res Date: 2012-09-26 Impact factor: 12.531