37. Mutation testing in non-small cell lung cancer - suitability of small biopsy and cytology specimens

Background Patients with non-small cell lung cancer (NSCLC) harbouring sensitising mutations in epidermal growth factor receptor ( EGFR) benefit from treatment with EGFR tyrosine kinase inhibitors. Most patients with NSCLC present with advanced-stage disease, so somatic mutation testing is often performed on small biopsy and cytology specimens. Aims To explore the suitability of small biopsy and cytology specimens for mutation testing in NSCLC. Methods Retrospective review of EGFR, KRAS, and BRAF mutation testing cases in NSCLC, performed at Royal Prince Alfred Hospital over 12 months using OncoCarta Panel v1.0 Kit and analysed on the SequenomMassArray platform and/or by direct sequencing and fragment analysis. Results and conclusions Mutation testing was undertaken on 123 NSCLC cases including 38 (30.9%) resection specimens, 54 (43.9%) small tissue biopsies and 31 (25.2%) cytology specimens. Two cases, both small biopsies, contained insufficient DNA for testing. Mutations were detected in 20/38 (52.6%) resection, 18/54 (33.3%) small biopsy, and 9/31 (29%) cytology specimens. EGFR mutations were identified in 11/38 (28.9%) resection, 6/54(11.1%) small biopsy, and 8/31 (25.8%) cytology cases. Compared to resection specimens, the proportion of EGFR -mutant cases was significantly lower in small biopsy (p — 0.03), but not in cytology specimens ( p = 0.77). The findings suggest small biopsy but not cytology specimens may be suboptimal for mutation testing in some cases, although selection bias of cases may contribute to these findings. Careful assessment of DNA quality and quantity is required in these circumstances, as limited DNA carries a risk of false negative or positive results.