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[369] Cytology Specimens Compare Favorably with Surgical Specimens for EGFR Mutation Detection in Patients with NSCLC

J Smouse, E Cibas, P Jänne, V Joshi, N Lindeman. Brigham and Womens Hospital, Boston, MA; Harvard Medical School, Boston, MA; Dana-Farber Cancer Institute, Boston, MA; Laboratory for Molecular Medicine, Cambridge, MA

Background: Somatic mutations in the epidermal growth factor receptor (EGFR) are present in 10-15% of non-small-cell lung cancers (NSCLC). NSCLC with these oncogenic mutations respond clinically to treatment with tyrosine kinase inhibitors (TKIs, gefitinib, erlotinib). Two mutations are common- a small in-frame deletion in exon 19 (45%) and an L858R point mutation in exon 21 (35%) - but other significant mutations have been reported. In order to detect all possible significant EGFR mutations, direct sequencing of tumor DNA is used, which is limited by interference from nonmalignant cells in the specimens, requiring manual microdissection to enrich the sample for cancer DNA before analysis. Concern over this interference has discouraged the testing of cytology samples, such that they have been used mostly when no adequate surgical material was available. This study aimed to determine whether or not cytology samples are suitable for EGFR sequencing.
Design: EGFR sequencing of surgical and cytology specimens at Brigham and Womens Hospital over the past two years was reviewed. 239 cases were analyzed, of which 227 were surgical specimens and 12 (5%) were cytology specimens, including FNAs, pleural fluids, bronchial washings, and BALs.
Results: Of the surgical specimens, 63 (27.8%) were positive for EGFR mutations, 143 (62.6%) were negative, 8 (3.5%) failed to amplify, and 14 (6.2%) were inconclusive (a negative result in a highly heterogeneous sample). Of the cytology specimens, 7 (58.5%) were positive for EGFR mutations, 4 (33%) were negative, and 1 (8.3%) was inconclusive. Cytology specimens showed significantly higher sensitivity for detecting mutations compared to surgical specimens (p=0.02). There was no significant difference in the frequency of inconclusive results. Mutations were detectable in cytology samples with as little as 25% tumor cellularity (of total nucleated cells).
Conclusions: Cytology specimens are suitable for EGFR sequencing and show higher sensitivity for mutation detection than do surgical specimens. Heterogeneous cytology specimens with modest tumor cellularity can be used for mutation detection (as low as 25% tumor cellularity in our study). The suitability of a sample should be determined on a case-by-case basis, and cytology samples should not be dismissed as inadequate without a thorough review.
Category: Cytopathology

Tuesday, March 27, 2007

Poster # 36, Tuesday Afternoon