Assessment of epidermal growth factor receptor (EGFR) and K-ras mutation status in cytologic stained smears of non-small cell lung cancer (NSCLC) patients.

Abstract

7560 Background: EGFR and K-ras mutations can help to guide treatment selection in NSCLC patients. Mutation status is routinely assessed in biopsy samples. Yet, lung cancer diagnosis relies to a large extent on cytological specimens which frequently are the only tumor samples available. We assessed EGFR and K-ras mutations in Papanicolau stained slides and cytological samples from NSCLC patients. Methods: DNA was extracted from cytological samples obtained by fine-needle aspiration (FNA) performed by bronchoscopy or ultrasound-guided endoscopy or from biological fluids. PCR and direct sequencing of exons 18-21 of EGFR gene and exon 2 of K-ras gene were performed using an ABI PRISM 310XL. Clinical activity of EGFR TKI was assessed and when biopsies were available, EGFR mutations were also determined in such samples. Results: From January 2007 to November 2009, 140 cytological samples were analyzed. DNA was extracted from: Papanicolau stained smears (111; 79%), cell block (9; 6%), fresh samples (9; 6%), ThinPrep (6; 4%) and body cavity fluids (5; 4%). Cytological diagnosis was: adenocarcinoma (101; 72%); other (39; 28%). EGFR mutations were found in 26 of 140 samples (19%) and K-Ras mutations in 14 of 126 (11%). In EGFR mutated cases, DNA was obtained from stained smears in 23 cases (88%), pleural fluid in 2 (8%) and cell block in 1 (4%). Response rate to EGFR tyrosine-kinase inhibitors in patients harbouring mutations was 75%. Paraffin-embedded tissue was also available from 12 patients. Mutation status of those samples showed 100% concordance with the cytology results. Conclusions: Assessment of EGFR and K-ras mutation status in cytological samples is feasible and their results and clinical applicability are similar to those obtained from biopsies. This technique allows extending the benefits of individualized treatment selection to NSCLC patients in which tumor biopsies are not available. No significant financial relationships to disclose.