子宫内膜癌分子亚型的免疫浸润特征分析  

Analysis of Immune Infiltration Characteristics in Molecular Subtypes of Endometrial Cancer

作　　者：郭晶晶 李婷 王历 罗丽莎 肖雪[1] GUO Jingjing;LI Ting;WANG Li(Department of Pathology,Sichuan Academy of Medical Sciences&Sichuan Provincial People′s Hospital,Chengdu Sichuan 610072,China;School of Medicine and Life Sciences,Chengdu University of Traditional Chinese Medicine,Chengdu Sichuan 610072,China)

机构地区：[1]四川省医学科学院·四川省人民医院病理科,四川成都610072 [2]成都中医药大学医学与生命科学学院,四川成都610072

出　　处：《实用妇产科杂志》2025年第4期312-318,共7页Journal of Practical Obstetrics and Gynecology

基　　金：四川省科技计划项目(编号:2022YFS0601)。

摘　　要：目的:从蛋白水平分析子宫内膜癌(EC)各分子亚型中免疫细胞的浸润情况,并探讨免疫浸润特征与临床病理特征的关联。方法:选取2013年1月至2021年1月在四川省人民医院病理科确诊的错配修复缺陷(MMR-D)型75例以及与之分化程度相当的错配修复完整(MMR-P)型74例EC患者临床资料,根据ProMisE标准分型,采用免疫组织化学(IHC)及多重荧光免疫组化(F-mIHC)定量分析CD8^(+)T细胞、调节性T细胞(Tregs)及巨噬细胞的分布情况,并探究各亚型的临床病理特征及免疫浸润情况。结果:149例样本中,MMR-D型75例、POLE突变(POLEmut)型8例、p53突变(p53abn)型13例、p53野生(p53wt)型53例。所有样本中,CD8^(+)T细胞、Tregs及巨噬细胞的浸润特征在不同年龄及病理分期间差异均无统计学意义(P>0.05)。在EC各分子亚型中,相比MMR-P型,MMR-D型肿瘤中的CD8^(+)T细胞和Tregs的密度更高(P<0.05)。对比4种分子亚型,预后较好的MMR-D型肿瘤中CD8^(+)T细胞密度显著高于p53abn型和p53wt型(P<0.05),Tregs密度显著高于p53wt型(肿瘤区域P<0.05,间质区域P<0.05);预后最好的POLEmut型肿瘤中CD8^(+)T细胞、Tregs密度与p53abn型和p53wt型比较,差异无统计学意义(P>0.05);p53wt型肿瘤预后中等,与MMR-D型比较,其CD8^(+)T细胞(P<0.05)和Tregs(肿瘤区域P<0.05,间质区域P<0.05)密度均较低;预后最差的p53abn型肿瘤区域中M2型巨噬细胞密度高于MMR-D型(P<0.05)和p53 wt型(P<0.05),CD8^(+)T细胞密度低于MMR-D型(P<0.05),且M1型巨噬细胞密度与其他亚型相比无差异(P>0.05)。结论:EC微环境中免疫细胞浸润特征与临床病理特征之间未见显著关联。而各分子亚型中,浸润性免疫细胞种类及分布差异显著,提示各EC分子亚型具有不同的免疫细胞浸润特征,且与患者的预后密切相关。Objective:To analyze the infiltration of immune cells in different molecular subtypes of endometrial cancer(EC)at the protein level and explore the correlation between immune infiltration and clinicopathological features.Methods:Clinical data from 75 mismatch repair-deficient(MMR-D)EC cases and 74 mismatch repair-proficient(MMR-P)EC cases with comparable differentiation levels,diagnosed at Sichuan Provincial People′s Hospital between January 2013 and January 2021,were selected.Molecular classification of EC was conducted according to the ProMisE standard.Immunohistochemistry(IHC)staining and fluorescent multiplexed immunohistochemistry(F-mIHC)techniques were used to quantify the distribution of CD8^(+)T cells,regulatory T cells(Tregs),and macrophages.The clinicopathological features and immune infiltration characteristics of different subtypes were investigated.Results:Among 149 samples,75 were MMR-D,8 were POLE-mutated(POLEmut),13 were p53-mutated(p53abn),and 53 were p53 wild-type(p53wt).The infiltration characteristics of CD8^(+)T cells,Tregs,and macrophages were no statistically significant differences correlated with age and pathological stage(P>0.05).Among the molecular subtypes of EC,MMR-D tumors demonstrated a significantly higher density of CD8^(+)T cells and Tregs compared to MMR-P tumors(P<0.05).Further comparison across the four EC molecular subtypes revealed that the MMR-D subtype,which had a favorable prognosis,displayed a significantly high density of CD8^(+)T cells compared to the p53abn subtype and the p53wt subtype(P<0.05).Additionally,the Tregs density of the MMR-D tumors was significantly higher than that of the p53wt tumors,in both the tumor area(P<0.05)and the stroma area(P<0.05).The POLEmut type tumors,which had the best prognosis,showed a high infiltration of CD8^(+)T cells and Tregs cells compared to the p53abn and p53wt types,although there was no significant statistical difference(P>0.05).The p53wt subtype,which had a moderate prognosis,exhibited low density of CD8^(+)T cells(P<0.05)an

关 键 词：子宫内膜癌 肿瘤微环境 分子分型 免疫浸润 

分 类 号：R737.33[医药卫生—肿瘤]