EGFR mutations are detected comparably in cytologic and surgical pathology specimens of nonsmall cell lung cancer

• Published in: Cancer 2009-02, Vol.117 (1), p.67-72
• Main Authors: Smouse, Jason H., Cibas, Edmund S., Jänne, Pasi A., Joshi, Victoria A., Zou, Kelly H., Lindeman, Neal I.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biological and medical sciences; Biopsy, Fine-Needle; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Non-Small-Cell Lung - surgery; Cytodiagnosis - methods; Cytological Techniques; cytology; DNA Mutational Analysis - methods; epidermal growth factor receptor; Female; Humans; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Lung Neoplasms - surgery; Male; Medical sciences; Middle Aged; Mutation; nonsmall cell lung cancer; Pathology, Surgical - methods; Pneumology; Receptor, Epidermal Growth Factor - genetics; surgical pathology; Tumors; Tumors of the respiratory system and mediastinum
• ISSN: 1934-662X; 0008-543X; 1934-6638; 1097-0142
• DOI: 10.1002/cncy.20011

BACKGROUND: Somatic mutations in the epidermal growth factor receptor (EGFR) are present in ∼10% of nonsmall cell lung cancers, and higher in never‐smokers, women, and Asians. Small in‐frame deletions in exon 19 (∼45%) and L858R mutation in exon 21 (∼40%) predict response to treatment with tyrosine kinase inhibitors, whereas some others herald resistance. Direct sequencing of tumor DNA detects all EGFR mutations, but is limited by interference from nonmalignant cells within the samples. Concern over such interference has discouraged testing cytologic samples, but the adequacy of cytologic specimens for EGFR sequencing has not been studied. METHODS: EGFR sequencing of surgical and cytologic specimens at Brigham and Women's Hospital over the past 2 years was reviewed. Of 239 specimens, 227 (95%) were surgical, and 12 (5%) were cytologic (fine needle aspirations, pleural fluids, bronchial washings, and bronchoalveolar lavages). RESULTS: Sixty‐three (28%) surgical specimens showed EGFR mutations, whereas 143 (63%) were negative, 8 (3.5%) failed, and 14 (6.2%) were inconclusive (negative result in a heterogeneous sample). Seven (58%) cytologic specimens showed EGFR mutations, whereas 4 (33%) were negative, and 1 (8.3%) was inconclusive. Cytologic specimens were more likely to have a mutation than surgical specimens (P = .02). There was no significant difference in the frequency of inconclusive results. CONCLUSIONS: Cytologic specimens are suitable for EGFR sequencing and show comparable sensitivity for mutation detection as compared with surgical specimens. The suitability of a sample should be determined on a case‐by‐case basis, and cytologic samples should not be dismissed as inadequate without a thorough review. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society. The claim that cytology specimens of lung adenocarcinoma are inadequate for genetic testing for EGFR mutations, which guide the use of tyrosine kinase inhibitor therapy, was investigated in a retrospective review. Cytologic specimens with at least 25% tumor cells were suitable for EGFR sequencing and showed comparable sensitivity for mutation detection as compared with surgical biopsy or resection specimens.