22. The utility of cytologic specimens for the assessment of EGFR status in lung cancer

Abstract

<h3>Background</h3> EGFR mutation status is a predictive marker for response and progression-free survival in patients with advanced lung adenocarcinoma and is recommended in diagnostic work-up to guide the use of tyrosine kinase inhibitors (TKI). There is little published data on the utility of material obtained by cytology methods for molecular analysis. Cytologic specimens can be successfully used for EGFR mutational analysis, importantly as this minimally invasive procedure may yield the only pathologic material guiding therapy in patients with unresectable tumour. <h3>Aims</h3> To compare detection of EGFR mutations in cytologic specimens versus biopsy samples. <h3>Methods</h3> A retrospective analysis of lung cancer patients with EGFR testing by molecular methods was performed. This included samples reported as (1) primary lung adenocarcinoma, (2) primary lung non-small cell lung carcinoma, (3) metastatic lung adenocar-cinoma, (4) metastatic poorly differentiated carcinoma. Biopsy methods included CT FNA, pleural fluid, CT biopsy and surgical resection. EGFR mutation analysis was performed by bidirectional dideoxy sequencing in exons 18, 19, 20 and 21. <h3>Results</h3> 268 samples were tested for EGFR mutational status. There were 35 (13%) activating mutations identified (exon 19 del, exon 21 L858R and exon 20 insertion). In addition 7 (3%) cases showed mutations of indeterminate significance. Material from cytology samples were used in 142 cases (53%) which included 19 (16%) activating mutations. There were 24 non-diagnostic cases due to too few cells for examination, of which 5 (4% of samples) were biopsy material and 19 (13% of samples) were cytologic material. <h3>Conclusion</h3> Cytology samples yielded similar results to biopsy and resection samples in detecting EGFR mutations in lung carcinoma. Non-diagnostic results were obtained more often in archival cytology samples than biopsy or resection specimens, due to fewer cells obtained for examination. Cytology being often the first and the preferred diagnostic sample for the evaluation of patients with suspected lung cancer, when triaged appropriately, material obtained by cytology is highly valuable for EGFR mutation analysis and yields comparable results to histology samples.