MLH1 promoter methylation-induced dMMR/MSS in endometrial cancer: case report

Endometrial cancer (EC) is a common malignant tumor in women, originating from the endometrial epithelium. Molecular classification of EC aids in guiding treatment, assessing prognosis, and screening for Lynch syndrome. Detection of mismatch repair (MMR) deficiency and microsatellite instability (MSI) status is crucial for guiding immunotherapy and Lynch syndrome screening. This study presents a case of poorly differentiated endometrioid carcinoma, which exhibited MMR deficiency but was microsatellite stable (MSS). Despite the MSS status, the tumor showed signs of genomic instability. Further MLH1 methylation testing suggested that MLH1 promoter methylation may have partially suppressed its expression. These results indicate that the immunohistochemistry (IHC) analysis yielded a negative result, whereas the MSI testing suggested that, although methylation of the MLH1 promoter allows MLH1 expression to largely maintain general genomic stability, it still exhibits signs of underlying instability. In conclusion, for endometrial cancer patients exhibiting dMMR by IHC but MSS by MSI testing, MLH1 promoter methylation testing becomes even more critical. This not only aids in screening for Lynch syndrome, enabling pathologists to make a more precise diagnosis, but also provides important guidance for clinical treatment decisions.