Could Mismatch Repair Status Serve as a Biomarker for Immunotherapy in Endometrial Carcinoma?

Abstract

Aim: To study whether mismatch repair (MMR) status is related to the expression of programmed cell death-ligand 1 (PD-L1) and CD8 counts in a series of grade 3 endometrial carcinomas.

Materials and methods: The expression of MMR protein PD-L1 and CD8⁺ cell count were evaluated by immunohistochemistry and related to several clinicopathological parameters.

Results: Among 105 endometrial carcinomas, 40% were of endometrioid and 60% of non-endometrioid histology. MMR deficiency was observed in 28.6% of cases and was related to endometrioid histology (p<0.001), positive PD-L1 expression (p=0.047) and high CD8⁺ cell count (p=0.022). When examined by histotype, endometrioid MMR-deficient tumors were related only to PD-L1 expression (p=0.032) but not to high CD8+ cell count (p=0.231), whereas non-endometrioid MMR-deficient carcinomas were not related to either of these markers. MMR deficiency was associated with PD-L1⁺/CD8^high status (p=0.006), whilst MMR proficiency was associated with PD-L1^-/CD8^low status. In MMR-proficient tumors, high CD8⁺ cell infiltration alone and combined with PD-L1^- status was associated with better progression-free survival (p=0.013 and p=0.04, respectively).

Conclusion: MMR-deficient high-grade endometrioid tumors might be more likely to benefit from immunotherapy compared to other grade 3 endometrial carcinomas.

Keywords: CD8; MMR; PD-L1; endometrial cancer.