Clinicopathologic characteristics, tumor infiltrating lymphocytes and programed cell death ligand-1 expression in 162 endometrial carcinomas with deficient mismatch repair function. Issue 1 (January 2019)

• Record Type: Journal Article
• Authors: Chavez, Jesus A; Wei, Lai; Suarez, Adrian A; Parwani, Anil V; Li, Zaibo
• Is Part Of: International journal of gynecological cancer. Volume 29:Issue 1(2019)
• Publication Date: 2019-01
• Subjects: Generative organs, Female -- Cancer -- Periodicals; 616.99465
• DOI: 10.1136/ijgc-2018-000042
• Languages: English
• ISSNs: 1048-891X

Abstract

Abstract : Objective: Endometrial carcinoma (EC) with deficient mismatch repair (dMMR) protein has been reported to have increased tumor infiltrating lymphocytes (TILs) and programed cell death ligand-1 (PD-L1) expression. TILs and PD-L1 expression are compared between two main types of dMMR ECs (epigenetic dMMR due to MLH1 promoter methylation vs mutated dMMR due to genetic mutation). Methods: Immunohistochemistry for PD-L1 was performed in triplicate on tissue microarray sections. TILs were semi-quantitatively evaluated on whole-slide images of whole histologic sections. The clinicopathologic characteristics together with PD-L1 expression and TILs were analyzed between mutated and epigenetic dMMR ECs. Results: Of the 162 dMMR ECs identified, 126 had epigenetic dMMR and 36 had mutated dMMR. Univariate analysis demonstrated mutated dMMR ECs showed younger age, less myometrium invasion of >50%, less lymphovascular invasion, and more TILs than epigenetic dMMR ECs. Multivariate analysis demonstrated significantly younger age and more TILs in mutated dMMR ECs than in epigenetic ECs. PD-L1 expression did not show any significant difference between these two groups. Seventeen (13.5%) patients with epigenetic dMMR EC had recurrence and 13 (10.3%) patients died of disease. In contrast, only one patient with mutated dMMR EC had recurrence (3%) and died of disease (3%). Conclusion: ECs with mutated dMMR demonstrated significantly increased TILs than ECs with epigenetic dMMR, suggesting a stronger immune reaction and potential response to immunotherapy in these tumors.