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Clinicopathologic characteristics, tumor infiltrating lymphocytes and programed cell death ligand-1 expression in 162 endometrial carcinomas with deficient mismatch repair function
  1. Jesus A Chavez1,
  2. Lai Wei2,
  3. Adrian A Suarez1,
  4. Anil V Parwani1 and
  5. Zaibo Li1
  1. 1 Department of Pathology, Wexner Medical Center at The Ohio State University, Columbus, Ohio, USA
  2. 2 Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University, Columbus, Ohio, USA
  1. Correspondence to Zaibo Li, Department of Pathology, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA; Zaibo.Li{at}osumc.edu

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.

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Footnotes

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Ethics approval This study was approved by the institutional review board of The Ohio State University Wexner Medical Center.

  • Provenance and peer review Not commissioned, externally peer reviewed.

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