Endometrial carcinosarcoma, also known as malignant mixed Mullerian tumor, is defined as a biphasic, malignant tumor composed of both carcinomatous and sarcomatous components that arise in the uterus, ovary, fallopian tube, and peritoneum [1]. Endometrial carcinosarcoma has an aggressive clinical course and the impact of surgery and adjuvant chemotherapy is limited for patients with recurrence and metastasis. So, new treatment options are needed.

Immune checkpoint inhibitor therapy, particularly involving the programmed death-1 (PD-1) pathway, may be a promising treatment option for endometrial carcinosarcoma. However, the significance of the PD-1 pathway and the tumor microenvironment in endometrial carcinosarcoma has not yet been clarified. PD-1 pathway has a critical role in tumor escape and is an inhibitory regulator of T-cells in the tumor microenvironment. PD-ligands, expressed on tumor cells and tumor-infiltrating lymphocytes (TILs), bind to PD-1 on the TILs and subsequently suppress the activation of cytotoxic T-cells. PD-1 has two main ligands called PD-1 ligand 1 (PD-L1) and PD-1 ligand 2 (PD-L2) [2]. In the recent literature, several studies have reported the importance of PD-L1 expression and the immune microenvironment in carcinosarcoma. However, there is no data about PD-L2 expression in endometrial carcinosarcoma.

Microsatellites are present in many regulatory genes, tumor suppressors, pro-apoptotic, and oncogenes and the deficiency of the Mismatch repair (MMR) system have been shown to be early molecular alteration in a subset malignancy and eventually gives rise to multiple cancer-associated mutations that can trigger oncogenesis [3]. The mutation in one of the repair proteins leads to impairment of the DNA MMR system. MMR deficiency has been identified in various cancer types, including gynecological cancers [4]. MMR protein deficiency is clinically significant for predicting response to immunotherapy. Patients with MMR protein deficient tumors are known to benefit more from PD-1/PD-L1 checkpoint inhibitor therapy [5].

In this study, we investigated the expression of PD-L1, PD-L2, and MMR proteins such as MSH-2, MSH-6, PMS-2, MLH-1, and CD8 positive TILs in the endometrial carcinosarcoma and analyzed their prognostic value. To the best of our knowledge, this was the first study to reveal the association between PD-L1/PD-L2 expression and MMR protein status and the tumor microenvironment in the same series of endometrial carcinosarcoma.