Endometrial carcinomas are associated with which of the following?

• A. MSI
• B. KRAS
• C. ALK
• D. CEA

Answer: (A)

Microsatellite instability arising from defective DNA mismatch repair is a key molecular feature of endometrial carcinomas. When the mismatch repair system fails—often due to loss of MMR genes like MLH1, MSH2, MSH6, or PMS2—microsatellites become unstable, producing many mutations across the genome. This MSI-high status is especially common in endometrioid endometrial cancers and is a hallmark that can point to Lynch syndrome in patients and families. Clinically, MSI-H tumors have implications for prognosis and, importantly, for therapy, since they tend to respond well to immune checkpoint inhibitors.

KRAS mutations can occur in endometrial cancers but are not a defining or universal feature. ALK alterations are more characteristic of other tumor types, such as certain lung cancers. CEA is a nonspecific tumor marker seen in various cancers, not a distinctive attribute of endometrial carcinoma.