Lynch syndrome accounts for approximately 3% of endometrial carcinomas. The Amsterdam II criteria and Revised Bethesda guidelines identify risk. In Lynch syndrome, which MMR gene mutation is most specifically associated with endometrial carcinoma predominance over colorectal carcinoma?
- A MLH1
- B MSH2
- C MSH6 ✓
- D PMS2
Explanation
MSH6 germline mutations in Lynch syndrome are characteristically associated with a predominance of endometrial carcinoma (lifetime risk 71%) over colorectal carcinoma, and they tend to present at older age. In contrast, MLH1 and MSH2 mutations more typically present with colorectal cancer as the index cancer. MSH6-associated Lynch syndrome also tends to be associated with less prominent familial patterns and may not fulfil Amsterdam II criteria, making reflexive MMR IHC testing of all endometrial carcinomas (universal MMR testing) critically important, as recommended by NCCN, SGO, and ESGO 2021.
Reference: Shaw's Textbook of Gynaecology, 17th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.