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Poorly differentiated neuroendocrine carcinoma (NEC) is a rare subtype of colorectal cancer (CRC). This study aimed to investigate clinicopathologic characteristics of colorectal NECs and elucidate genomic differences and similarities between colorectal NECs and colorectal adenocarcinomas (ACs). A total of 30 colorectal NECs were screened for frequently identified CRC oncogenic driver genes by targeted next-generation sequencing of 382 genes. The median age of the patients was 67 years (range, 44 to 88 years). NECs occurred predominantly in the rectum (47%) and exhibited multiple adverse prognostic pathologic factors, including frequent lymphatic and vascular invasions, high rates of lymph node metastasis and distant metastasis and advanced TNM stage. The 1-, 3-, and 5-year overall survival rates of NEC patients were 46.7%, 36.4%, and 32.7%, respectively, with a median overall survival period of 11.5 months. In a molecular analysis, NECs showed high rates of  BRAF  mutation (23%), predominantly p.V600E (71%), and alterations in  RB1  (47%), particularly deletion (57%). The frequencies and distributions of other genes, such as  KRAS ,  APC ,  SMAD4 , and  PIK3CA , and microsatellite instability status were similar to those of ACs. These findings provide beneficial information for selecting therapeutic options, including targeted therapy, and a better understanding of the histogenesis of this tumour.

Comprehensive analysis of mutational and clinicopathologic characteristics of poorly differentiated colorectal neuroendocrine carcinomas