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.
