Reflex testing of lung adenocarcinomas for EGFR and KRAS mutations: The Memorial Sloan-Kettering experience.

22031 Background: Primary lung adenocarcinoma is preferentially susceptible to tyrosine kinase inhibitors (TKI). Identification of activating mutations in EGFR TK domain is thr best predictor for sensitivity/response to EGFR TKIs. These mutations are not found in association with KRAS mutations. The presence of a KRAS mutation contraindicates EGFR TKI therapy indicating other agents, or investigational therapies. Given the high rate of recurrence of adenocarcinoma, and frequent difficulties/delays in obtaining archival material for molecular testing at recurrence (necessitating in some patients a second procedure), we instituted routine reflex testing for EGFR and KRAS mutations of all resected lung adenocarcinomas.,At the time of gross prosection, a slice of tumor is frozen and retained along with a corresponding section for paraffin embedding and H&E staining. When histology shows adenocarcinoma, frozen tissue and corresponding H&E slide are sent to the molecular diagnostic laboratory for extraction of DNA and identification of EGFR exon 19 deletions and exon 21 L858R mutations by PCR assays. In samples lacking EGFR mutations, KRAS analysis is done by direct sequencing of PCR products. If frozen tissue is unavailable, the paraffin block serves as an alternate source of DNA. A molecular diagnostic report is issued to the clinician before the patient's post-op or oncology visit, and becomes part of the medical record.,Reflex testing started in 2006. In a one year period, over 500 lung resections were performed. 297 adenocarcinomas, including wedge resection, segmentectomy, lobectomy, bilobectomy, and pneumonectomy were successfully studied. 294 (98%) of cases were studied for both EGFR and KRAS. There were 58 (20%) EGFR mutant cases and 85 (28%) KRAS mutant cases. Interestingly, there were 13 Asian patients with an EGFR mutation rate of 53% and no KRAS mutations; 11 black patients had a 9% EGFR mutation rate and 45% KRAS mutation rate.,Mutations in exons 19 and 21 of EGFR and exon 2 of KRAS are common in resected specimens from patients with lung adenocarcinoma. Reflex testing for EGFR and KRAS mutations is easily implemented and ensures that key molecular data are available to inform and expedite subsequent treatment decisions. No significant financial relationships to disclose.