Differentiation between squamous cell carcinoma (SCC) and adenocarcinoma (AC): Expression of immunohistochemical (IHC) markers in a tissue microarray (TMA) of >1000 NSCLC

Introduction: Distinguishing SCC from AC has become crucial for tailored therapies of NSCLC. Many patients are inoperable at the time of diagnosis of NSCLC, >65% of the diagnoses are performed in small biopsies (Bx). The “IASLC/ATS/ERS international multidisciplinary classification of lung adenocarcinoma” (Travis W.D., Brambilla E. et al. JTO 2011; 6:244-85) firstly includes diagnostics in Bx in addition to resection specimen. We investigated the expression of IHC markers in a TMA simulating Bx. Materials and methods: The IHC markers CK5/6, p63, desmocollin-3, CK7, TTF1, and napsin were investigated in a TMA from a primary cohort of 1005 patients with resected NSCLC. Results: For SCC, desmocollin-3 showed the highest, CK5/6 a medium, and p63 the lowest specifity. The sensitivity of desmocollin-3 was similar to the combined sensitivity of CK5/6 and p63. Desmocollin-3 was expressed in about 85%, CK5/6 and p63 in >90% of all SCC. For AC, TTF1 and napsin revealed a considerably higher specifity than CK7. The sensitivity of napsin did not exceed the combined sensitivity of CK7 and TTF1. CK7 was expressed in >95% of all AC, TTF1 in <90%, and Napsin in <80%. Conclusions: To spare tumor tissue for further (e.g. molecular) analyses, diagnostic algorithms for NSCLC Bx must be established. If histology alone cannot distinguish between SCC and AC, a combination of TTF1, napsin, CK5/6 and desmocollin-3 can serve as initial diagnostic marker panel. CK7 and p63 could be used subsequently, if necessary, because of lower specifity. Currently a TMA of 300 further NSCLC is investigated, data from all 1300 NSCLC will be presented.