Assessment of mismatch repair protein expression by immunohistochemistry in endometrial carcinomas with clinicopathological correlation: A study from Indian Tertiary Cancer Care Centre

Abstract

Objectives: Endometrial carcinomas (EC) are known to be histologically and biologically heterogeneous, and their recent molecular characterization has highlighted their etiologic heterogeneity. The aim of the present study was to analyze mutations in mismatch repair (MMR) proteins in ECs by immunohistochemistry (IHC), and correlates the data with their pathological parameters. Material and Methods: The expression of MMR proteins was analyzed using IHC in VENTANA BENCHMARK XT system, on formalin-fixed paraffin-embedded tumor tissue. The study population included 102 newly diagnosed cases of ECs over a duration of 2 years. Results: On histopathologic subtyping, 85.1% of cases were of Type 1 EC, 9.8% were Type 2 EC, and 4.9% were malignant mixed Mullerian tumors. On IHC for MMR protein expression, 22 of 102 cases (21.6%) showed loss of one or more protein, and mean age of patients with deficient MMR (dMMR) was 59.6 years. All of these dMMR cases were of endometrioid subtype, forming 25.3% of EEC. The combined loss of MLH1 and PMS2 was the most common abnormality detected (50% of dMMR). On pathological correlation, 54.5% of dMMR cases were found to be of higher grade (grade 2/3; P = 0.002) and 68.2% were higher stage tumors (T1b and above; P < 0.0001). The lymph-vascular invasion was seen in 50% of dMMR cases (4 of 8 cases). Conclusion: Detecting MMR protein loss in ECs by IHC is an efficient, relatively simple, and economical method. It needs to be routinely performed in all cases of ECs. Studies are still underway to utilize it as a therapeutic modality using immunotherapy.