Reflex testing of resected stage i through III lung adenocarcinomas for EGFR and KRAS mutation: Report on initial experience and clinical utility at a single center Journal Article


Authors: D'Angelo, S. P.; Park, B.; Azzoli, C. G.; Kris, M. G.; Rusch, V.; Ladanyi, M.; Zakowski, M. F.
Article Title: Reflex testing of resected stage i through III lung adenocarcinomas for EGFR and KRAS mutation: Report on initial experience and clinical utility at a single center
Abstract: Objective: The genes KRAS and EGFR have emerged as potential targets for therapy in lung adenocarcinoma; mutations in these genes can be found in almost half of patients. In anticipation of the clinical importance of molecularly defined adenocarcinoma subgroups for the treatment of patients with resected stages I through III lung adenocarcinoma, the Memorial Sloan-Kettering Cancer Center (MSKCC) Departments of Surgery and Pathology have collaborated since 2006 to conduct reflex testing of tumor specimens for EGFR and KRAS mutations. Methods: Using established methods, the identification of EGFR exon 19 deletions and exon 21 L858R mutations was performed. In samples lacking these 2 sensitizing EGFR mutations, KRAS analysis was done. Results: We studied a total of 1831 patients who had stage I through IV lung adenocarcinomas and detected 448 KRAS and 364 EGFR mutations. Of these patients, a subset of 855 (78%) patients with stages I through III adenocarcinoma of the lung who underwent curative surgical resection at MSKCC were tested. In patients with early stage disease, 158 EGFR mutations and 207 KRAS mutations were detected. Conclusions: The results of the first 3 years of reflex testing at MSKCC reported here demonstrate the feasibility, clinical utility, and potential of this approach. This information allowed for enrollment of patients into clinical trials to explore mutation-specific, directed therapy and led to retrospective studies related to patient outcome. In addition, it may inform selection of chemotherapy for recurrent disease and may help to distinguish multiple primary tumors from metastatic disease. Copyright © 2011 by The American Association for Thoracic Surgery.
Keywords: human tissue; cancer surgery; gene mutation; major clinical study; exon; gene deletion; histopathology; cancer staging; genetic analysis; epidermal growth factor receptor; lung adenocarcinoma; feasibility study; k ras protein; reflex testing
Journal Title: Journal of Thoracic and Cardiovascular Surgery
Volume: 141
Issue: 2
ISSN: 0022-5223
Publisher: Mosby Elsevier  
Date Published: 2011-02-01
Start Page: 476
End Page: 480
Language: English
DOI: 10.1016/j.jtcvs.2010.08.026
PROVIDER: scopus
PUBMED: 20933246
DOI/URL:
Notes: --- - "Export Date: 4 March 2011" - "CODEN: JTCSA" - "Source: Scopus"
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MSK Authors
  1. Valerie W Rusch
    739 Rusch
  2. Christopher G Azzoli
    111 Azzoli
  3. Marc Ladanyi
    1063 Ladanyi
  4. Maureen F Zakowski
    287 Zakowski
  5. Bernard J Park
    175 Park
  6. Sandra Pierina D'Angelo
    144 D'Angelo
  7. Mark Kris
    729 Kris