Many studies have shown that p16 is positive in LCNEC, and the IHC expression rate is approximately 57%–77.5%, which is lower than that in SCLC, but overall studies suggest that retinoblastoma (RB1) positive, cyclin D1 positive, and p16 negative patterns in IHC are more common in LCNEC [56–58]. Here, RB1 is linked to large cell neuroendocrine carcinoma.