To further clarify the molecular features of colorectal neuroendocrine carcinomas (NECs), we immunohistochemically examined tumor samples from 25 NECs, including 9 small cell NECs (SCNECs) and 16 large cell NECs (LCNECs), 20 neuroendocrine tumors (NETs), and 21 poorly differentiated adenocarcinomas (PDCs) for the expression of several biomarkers (p53, β-catenin, Bcl-2, Rb, p16, p21, cyclin D1, and cyclin E) and used sequencing analysis to identify gene alterations of TP53, APC, CTNNB1, KRAS, and BRAF.
FLI-1 was expressed in 63% of solid pseudopapillary neoplasms, but only in 1/22 pancreatic neuroendocrine tumors (5%), cyclin D1 expression was present in 14% of the latter.
We have previously demonstrated that cyclin D1 is constitutively expressed in human BON neuroendocrine tumour cells due to an autocrine insulin-like growth factor-I (IGF-I) loop.
Overexpression of cyclin D1 in the parathyroid glands of mice resulted in the tandem regulation of cellular proliferation and hormonal secretion, a feature intrinsic to neuroendocrine tumors.