: Lynch Syndrome and Hereditary Endometrial Cancer
Approximately 3% to 5% of all endometrial cancer cases are linked to Lynch Syndrome, an autosomal dominant hereditary condition caused by germline mutations in DNA mismatch repair (MMR) genes, such as $MLH1$, $MSH2$, $MSH6$, or $PMS2$.
Women with Lynch Syndrome have a lifetime risk of developing endometrial cancer ranging from 40% to 60%, which often equals or exceeds their risk of developing colorectal cancer.
Modern clinical guidelines now recommend universal screening of all endometrial tumors using Immunohistochemistry (IHC) to check for the presence or absence of these four MMR proteins. If a "loss of expression" is found, the patient is referred for genetic counseling and germline testing. Identifying Lynch Syndrome is life-saving, as it mandates a specialized surveillance program for the patient (including frequent colonoscopies) and triggers "cascade testing" for their biological relatives, who may also be at high risk for multiple cancers.