What are the genetic abnormalities in conventional CRCs?
• Colorectal adenocarcinomas usually arise from adenomas and can be sporadic (85%) or syndromic. These are graded as well, moderately, or poorly differentiated based on the glandular differentiation. The variants include mucinous (greater than 50% mucinous morphologic characteristics) and signet ring cell carcinomas (greater than 50% signet ring cell morphologic characteristics). Histologically, neoplastic glands with necrotic debris show invasion through the muscularis mucosa into the submucosa or beyond. On immunohistochemistry (IHC), these usually show staining with cytokeratin 20 and CDX2, and are usually negative for staining with cytokeratin 7. The most common genetic alteration (somatic) in sporadic CRCs is inactivation of APC/beta-catenin pathway that can have multiple consequences. Clonal accumulation of additional genetic alterations then occurs, including activation of proto-oncogenes such as c-myc and ras and inactivation of additional tumor suppressor genes ( TP53 on chromosome 17). These tumors are microsatellite stable (MSS). BRAF mutation is not common and seen in a few (less than 10%) conventional CRCs.
Small cell carcinoma is a rare variant of CRC with poor prognosis, which shows small cell morphologic characteristics and positive immunostaining with neuroendocrine markers such as chromogranin, synaptophysin, and NCAM (CD56). These are not associated with carcinoid tumors (well-differentiated neuroendocrine tumors) and may be seen with conventional CRC.