Mismatch Repair Deficiency in Endometrial Cancer: Immunohistochemistry Staining and Clinical Implications

DNA mismatch repair (MMR) deficiency is associated with increased risk of developing several types of cancer and is the most common cause of hereditary endometrial cancer. Identification of the microsatellite instability (MSI) phenotype in endometrial carcinoma is important given that such tumors are frequent.

The objective of this study was to assess the utility of immunohistochemistry (IHC), a simple and fast technique, in detecting MSI status in endometrial carcinoma and evaluate the correlation between the MSI phenotype and the various anatomo-clinical parameters.

IHC expression of 4 markers (MLH1, MSH2, PMS2, and MSH6) was studied. For all IHC markers, a combined score based on the intensity of nuclear labeling and the percentage of labeled cells was defined to establish a score. Correlation between MSI phenotype and different clinicopathologic parameters was evaluated using statistical analysis (software STATA and the Fisher exact test).

The mean age of the patients was 58.6 years. Positive staining was highly extended (score 3) with 79% to 100% of marked cells. Less than 10% of positive tumor cells were seen in 3% of cases for MSH6 and PMS2. Abnormal MMR IHC was detected in 10 cases (22.22%). Seven tumors showed loss of MLH1/PMS2. The loss of MSH2/MSH6 was observed in 1 case. The loss of MLH1 or PMS2 was seen only in 2 cases. The number of MSI positive status was 10 cases (22.7%). Correlation between clinicopathologic parameters showed MMR deficiency was significantly associated with low-grade tumor and localized stage. There was no positive correlation between age, histologic subtype, or myometrium invasion.

In summary, detection of DNA MMR deficiencies by IHC can effectively diagnose the MSI phenotype in endometrial carcinoma. Correlation between clinicopathologic parameters showed MMR deficiency was significantly associated with low-grade tumor and localized stage.