Clinical Significance of Tumor Immune Microenvironment in Endometrial Endometrioid Carcinoma, Grade 1 With DNA Mismatch Repair Protein Loss.

IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY International Journal of Gynecological Pathology Pub Date : 2024-11-01 Epub Date: 2024-01-22 DOI:10.1097/PGP.0000000000001020
Kazuhisa Hachisuga, Minoru Kawakami, Hiroshi Tomonobe, Shoji Maenohara, Keisuke Kodama, Hiroshi Yagi, Masafumi Yasunaga, Ichiro Onoyama, Kazuo Asanoma, Hideaki Yahata, Yoshinao Oda, Kiyoko Kato
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Abstract

The administration of immune checkpoint inhibitors (ICIs) is increasing in endometrial cancer, especially in the mismatch repair (MMR)-deficient group. To prevent unnecessary immune-related adverse events, ICIs need to be administered to more appropriate patients. The tumor immune microenvironment has been reported to be a predictive marker of the efficacy of ICI therapies. This study evaluated CD8, FoxP3, CD68, PD-L1, and β-catenin expression in endometrial endometrioid carcinoma, grade 1 (G1) with DNA mismatch repair protein loss (MMR loss), and their association with clinicopathological features. We retrospectively analyzed tumor samples from 107 patients with endometrial endometrioid carcinoma, G1 (MMR-deficient group: n=67; MMR-proficient group: n=40). Overall, 47 cases of MLH1/PMS2 loss and 20 cases of MSH2/MSH6 loss were observed. The patients with low intraepithelial CD8 expression significantly more frequently exhibited deep myometrial invasion, and the elderly group (≥60 y) significantly more frequently showed low stromal CD8 expression. In addition, FoxP3-positive cell count and FoxP3/CD8+ ratio were significantly correlated with the International Federation of Obstetrics and Gynecology 2023 stage and lymph node metastasis. In the Kaplan-Meier analysis, the patients with low intraepithelial or stromal CD8 expression had shorter progression-free survival (PFS) than those with high intraepithelial or stromal CD8 expression, albeit not significantly. We clarified that the tumor immune microenvironment had an impact on clinicopathological features within the group with MMR loss, which is the main target for ICIs, limited to endometrioid carcinoma, G1. Further studies are needed, including on patients administered ICIs.

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具有 DNA 错配修复蛋白缺失的 1 级子宫内膜样癌肿瘤免疫微环境的临床意义
在子宫内膜癌中,尤其是在错配修复(MMR)缺陷组中,使用免疫检查点抑制剂(ICIs)的情况越来越多。为了防止不必要的免疫相关不良事件,需要对更合适的患者使用 ICIs。据报道,肿瘤免疫微环境是 ICI 疗效的预测指标。本研究评估了具有DNA错配修复蛋白缺失(MMR缺失)的1级(G1)子宫内膜样癌中CD8、FoxP3、CD68、PD-L1和β-catenin的表达及其与临床病理特征的关系。我们回顾性分析了107例G1级子宫内膜样癌患者的肿瘤样本(MMR缺失组:n=67;MMR良好组:n=40)。总计观察到 47 例 MLH1/PMS2 缺失和 20 例 MSH2/MSH6 缺失。上皮内 CD8 低表达的患者明显更多表现为子宫肌层深部浸润,老年组(≥60 岁)明显更多表现为基质 CD8 低表达。此外,FoxP3阳性细胞数和FoxP3/CD8+比值与国际妇产科联盟2023分期和淋巴结转移显著相关。在 Kaplan-Meier 分析中,上皮内或基质 CD8 低表达患者的无进展生存期(PFS)短于上皮内或基质 CD8 高表达患者,尽管差异不明显。我们明确了肿瘤免疫微环境对MMR缺失组临床病理特征的影响,而MMR缺失是ICIs的主要靶点,仅限于子宫内膜样癌G1。还需要进一步研究,包括对使用 ICIs 的患者进行研究。
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来源期刊
CiteScore
3.90
自引率
12.50%
发文量
154
审稿时长
6-12 weeks
期刊介绍: International Journal of Gynecological Pathology is the official journal of the International Society of Gynecological Pathologists (ISGyP), and provides complete and timely coverage of advances in the understanding and management of gynecological disease. Emphasis is placed on investigations in the field of anatomic pathology. Articles devoted to experimental or animal pathology clearly relevant to an understanding of human disease are published, as are pathological and clinicopathological studies and individual case reports that offer new insights.
期刊最新文献
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