Mismatch repair deficiency is not associated with AMH/AMHR2 protein expression in endometrial carcinoma: implications for molecular stratification

Mismatch repair deficiency (MMR-d) defines a clinically relevant molecular subtype of endometrial carcinoma (EC), particularly for immunotherapy. Anti-Müllerian hormone (AMH) and its type II receptor (AMHR2) may modulate endometrial carcinogenesis, but their association with MMR-d remains unclear. This study investigated associations between MMR status and AMH/AMHR2 protein expression across histopathological subtypes and tumour stages. Tissue samples from 214 patients with EC were analysed. MMR status was assessed by immunohistochemistry (IHC), with RT-PCR–based microsatellite instability testing in selected cases. AMH and AMHR2 expression was assessed by IHC. Associations with molecular, clinicopathological, and reproductive variables were evaluated using generalised linear and logistic regression models, including interaction analyses. MMR-d was detected in 47/214 tumours (21.96%); MSI was confirmed in 35/47 (74.47%). AMH protein expression was detectable in 21/214 (9.81%) tumours (median patient-level mean IRS 0.0, Q1–Q3: 0.0–0.0), whereas AMHR2 protein expression was detectable in all 214 tumours (100%; median patient-level mean IRS 6.0, Q1–Q3: 4.7–8.0). Neither protein was significantly associated with MMR-d. AMH expression was associated with breastfeeding duration, body mass index, hypertension, FIGO stage and histopathological subtype; AMHR2 expression with histopathological subtype, diabetes and hormonal contraception. AMHR2 was detectable across FIGO stages without a consistent stage-related decline. The association between FIGO stage and MMR-d probability varied by tumour type. MMR-d was not significantly associated with AMH or AMHR2 expression. Tumour type-stage interactions suggest heterogeneity within the MMR-d subgroup. AMHR2 may have theranostic relevance, although its detection does not establish functional AMH signalling.