The role of the cytopathologist in subtyping and epidermal growth factor receptor testing in non-small cell lung cancer: An institutional experience.

Abstract

Approximately 10% of non-small-cell lung cancer (NSCLC) remains unclassifiable as NSCLC-not otherwise specified (NOS), after using a panel of immunomarkers. The present study was undertaken to assess sensitivity and specificity of immunomarkers in sub-typing NSCLC on fine needle aspiration cytology (FNAC). Epidermal growth factor receptor (EGFR) mutations were also detected in these samples. Sixty cases of NSCLC including 15 squamous cell carcinoma (SCC), 15 adenocarcinomas (ADC) and 30 NSCLC-NOS reported on FNAC were included in the study. A panel of CK7, CK5/6, TTF-1 and p63 was applied in these cases. DNA was extracted from 54 cases including 14 effusion samples, and EGFR mutations were detected. Classic ADC cases (n=15) showed 73.3% TTF-1 positivity and 100% CK7 positivity. Two cases of ADC showed aberrant expression of p63 and 2 cases showed CK5/6 positivity. 80% of classic SCC cases (n=15) showed strong nuclear p63 positivity and 86.6% were positive for CK5/6. TTF-1 was seen exclusively in ADC cases. Immunohistochemistry (IHC) using two immunomarkers (TTF-1 and p63) helped in subtyping 24/30(80%) cases of NSCLC. EGFR mutations were detected in 9/54 (16.7%) cases, and the most common mutation was short in-frame deletion in Exon 19. More than 90% of NSCLC can be sub-typed on cytology samples with the help of immunochemistry. The sensitivity of TTF-1, p63, CK5/6 and CK7 was 73.3%, 80%, 100% and 100%, respectively. The specificity of TTF-1, p63, CK5/6 and CK7 was 100%, 86.6%, 86.6% and 93.3%, respectively. TTF-1 is highly specific, and almost 80% of NSCLC-NOS cases can be sub-typed using TTF-1 and p63. EGFR mutations can be detected in cytology samples, and 16.7% samples were positive for EGFR mutations.