Gynecology and Obstetrics Unit, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy; Division of Gynaecology and Human Reproduction Physiopathology, Department of Medical and Surgical Sciences (DIMEC). IRCCS Azienda Ospedaliero-Univeristaria di Bologna. S. Orsola Hospital. University of Bologna, Via Massarenti 13, Bologna 40138, Italy.
Anatomic Pathology Unit, Department of Advanced Biomedical Sciences, School of Medicine, University of Naples Federico II, Naples, Italy.
Gynecol Oncol. 2021 May;161(2):621-628. doi: 10.1016/j.ygyno.2021.02.030. Epub 2021 Mar 12.
Polymerase-ε (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.
To assess TIL as histological surrogate of POLE mutation in EC.
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.
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.
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.
与 POLE 野生型子宫内膜癌 (EC) 相比，聚合酶-ε (POLE) 突变型子宫内膜癌 (EC) 显示出更多的肿瘤浸润淋巴细胞 (TIL)。然而，当缺乏分子数据时，TIL 是否有助于识别 POLE 突变型 EC 尚不清楚。POLE 突变替代物的鉴定对于在临床实践中转化 TCGA/ProMisE 风险评估可能至关重要。
评估 TIL 作为 EC 中 POLE 突变的组织学替代物。
从其成立到 2020 年 9 月，我们在七个电子数据库中搜索了允许提取有关 TIL 和 EC 的 TCGA/ProMisE 组的数据的研究。我们计算了 TIL 在区分 POLE 突变型与 i）POLE 野生型、ii）无特定分子谱 (NSMP)、iii）POLE 野生型/MMR 功能型、iv）MMR 缺陷型 EC 时的 pooled 敏感性、特异性、阳性和阴性似然比 (LR+ 和 LR-)、诊断比值比 (DOR) 和 SROC 曲线下面积 (AUC)。
纳入了 10 项研究，共纳入了 1169 名女性进行定性分析。TIL 高模式表现为：对 POLE 突变型 vs POLE 野生型 ECs 的敏感性 = 0.65，特异性 = 0.63，LR+ = 2.06，LR- = 0.48，DOR = 4.39，AUC = 0.7532；对 POLE 突变型 vs NSMP ECs 的敏感性 = 0.85，特异性 = 0.73，LR+ = 2.80，LR- = 0.22，DOR = 15.17；对 POLE 突变型 vs POLE 野生型/MMR 功能型 ECs 的敏感性 = 0.85，特异性 = 0.66，LR+ = 2.49，LR- = 0.25，DOR = 10.30；对 POLE 突变型 vs MMR 缺陷型 ECs 的敏感性 = 0.68，特异性 = 0.44，LR+ = 1.38，LR- = 0.64，DOR = 2.68，AUC = 0.6694。
在排除 MMR 缺陷型病例后，TIL 高模式在区分 POLE 突变型与 POLE 野生型 ECs 方面具有中等准确性。当测序不可用时，TIL 可能会被考虑纳入一种综合算法来识别 POLE 突变型 ECs。在这方面需要进一步的研究。
