Agreement of CK5/6, p40, and p63 immunoreactivity in non-small cell lung cancer

Histological subtyping of non-small cell lung cancer (NSCLC) is of utmost importance for therapy stratification. Common immunohistochemical markers to identify squamous lineage are CK5/6, p40, and p63. Although p40 is considered the gold standard by current guidelines, the agreement of all three markers is an important aspect for tumours more difficult to classify. A total of 1244 NSCLC including 569 squamous cell carcinomas (SqCC) and 675 adenocarcinomas were assembled on a tissue microarray and stained with CK5/6, p40, p63, TTF-1, and Napsin-A. Sensitivity and specificity for squamous lineage markers as well as agreement of CK5/6, p40 and p63 were calculated. Sensitivity of CK5/6, p40, and p63 for SqCC was 93%, 94%, and 94% and specificity was 98%, 97%, and 84%, respectively. Positivity for two of these markers was found in at least in 90% of SqCC. Highest agreement was observed for p40 and p63 (Cohen's kappa 0.80). We report a similar sensitivity of CK5/6, p40, and p63, but a decreased specificity of p63 as compared to CK5/6 and p40 for the identification of squamous lineage. Our results support the use of either CK5/6 or p40 over p63 in the routine diagnostic setting.