Tumor-infiltrating lymphocytes and POLE mutation in endometrial carcinoma

Background. Polymerase-epsilon (POLE)-mutated endometrial carcinomas (ECs) have displayed an increased number of tumor-infiltrating lymphocytes (TIL) compared to POLE-wild-type ECs. However, it is unclear if TIL may aid in identifying POLE-mutated ECs when molecular data are unavailable. The identification of a POLE mutation surrogate may be crucial to translate TCGA/ProMisE risk assessment in the clinical practice. Aim. To assess TIL as histological surrogate of POLE mutation in EC. Materials and methods. Seven electronic databases were searched from their inception to September 2020 for studies that allowed data extraction about TIL and TCGA/ProMisE groups of EC. We calculated pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), diagnostic odds ratio (DOR) and area under the curve (AUC) on SROC curves of TIL in distinguishing POLE-mutated from i) POLE-wild-type, ii) no specific molecular profile (NSMP), iii) POLE-wild-type/MMR-proficient, iii) MMR-deficient ECs. Results. 10 studies assessing 1169 women were included in the qualitative analysis. TIL-high pattern showed: sensitivity = 0.65, specificity = 0.63, LR + =2.06, LR-= 0.48, DOR = 4.39, AUC = 0.7532 for POLE-mutant vs POLE-wild-type ECs; sensitivity = 0.85, specificity = 0.73, LR + = 2.80, LR-= 0.22, DOR = 15.17 for POLE-mutant vs NSMP ECs; sensitivity = 0.85, specificity = 0.66, LR + = 2.49, LR-= 0.25, DOR = 10.30 for POLE-mutant vs POLE-wild-type/MMR-proficient ECs; sensitivity = 0.68, specificity = 0.44, LR + =1.38, LR-= 0.64, DOR = 2.68, AUC = 0.6694 for POLE-mutant vs MMR-deficient ECs. Conclusion. TIL-high pattern shows a moderate accuracy in distinguishing POLE-mutated from POLE-wild type ECs after the exclusion of MMR-deficient cases. TIL might be considered in an integrate algorithm to identify POLE-mutated ECs when sequencing is unavailable. Further studies are necessary in this regard. (c) 2021 Elsevier Inc. All rights reserved.

Automated summary

The TIL-high pattern shows moderate accuracy in distinguishing POLE-mutated from POLE-wild type ECs, especially after excluding MMR-deficient cases. TIL may be considered in an integrated algorithm to identify POLE-mutated ECs when sequencing is unavailable. Further studies are needed in this regard.