RB1 and large cell neuroendocrine carcinoma: Recently, multiple studies have shown that INSM1 has a hight expression in neuroendocrine neoplasms originated from multiple tissues, that included gastrointestinal, and is therefore a reliable marker for the diagnosis and differential diagnosis of neuroendocrine neoplasms.[16–18] According to the related research reported that the most common mutated genes is TP53 in LCNEC.[19] Meanwhile, inactivation of Rb gene protein is often presented in NEC.