Prognostic and clinical heterogeneity of PD1 and PD-L1- immunohistochemical scores in endometrial cancers

IF 2.1 3区 医学 Q2 OBSTETRICS & GYNECOLOGY
L. Proppe, T. Jagomast, S. Beume, F. Köster, K. Bräutigam, A. Rody, S. Perner, F. Hemptenmacher, J. Ribbat-Idel, L. C. Hanker
{"title":"Prognostic and clinical heterogeneity of PD1 and PD-L1- immunohistochemical scores in endometrial cancers","authors":"L. Proppe,&nbsp;T. Jagomast,&nbsp;S. Beume,&nbsp;F. Köster,&nbsp;K. Bräutigam,&nbsp;A. Rody,&nbsp;S. Perner,&nbsp;F. Hemptenmacher,&nbsp;J. Ribbat-Idel,&nbsp;L. C. Hanker","doi":"10.1007/s00404-024-07862-y","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><p>PD1/PD-L1 inhibition (ICi) has recently become a new standard of care for patients with advanced MMR-deficient (MMRd) endometrial cancers. Nevertheless, response to immunotherapy is more complex than the presence of a single biomarker and therefore it remains challenging to predict patients response to ICi beyond MMRd tumors. Elevated PD-L1 expression (CPS ≥ 1) is often used as a prognostic marker as well as a predictive biomarker of response to ICi in different tumor types. In a retrospective, patient derived study, we analyzed PD1- and PD-L1 staining and correlated the results of different scores to clinical data to evaluate the prognostic impact of these scores.</p><h3>Materials and methods</h3><p>Immunohistochemical analysis of the receptor PD1 and the receptor ligand PD-L1 were performed on TMAs of primary paraffin‑embedded tumor samples. All patients were treated for primary endometrial cancer in the Department of Gynecology and Obstetrics, University Medical Center Schleswig–Holstein, Campus-Lübeck, Germany between the years 2006–2018. The evaluation and determination of the tumor proportion scoring (TPS), the combined positive score (CPS) and the immune cell scoring (IC) was automatically assessed semi-quantitatively, and results were correlated with clinicopathological characteristics and survival.</p><h3>Results</h3><p>130 samples were evaluable and 64% showed a positivity (IC &gt; 0) for the receptor PD1 and 56% for the receptor ligand PD-L1. Patients with a PD1 IC Score ≥ 1 showed a significant longer disease-free survival of 140 months (95% confidence interval (CI): 124–158) compared to patients with a lower IC &lt; 1 for PD1 of 89 months (95% confidence interval (CI): 69–110); <i>p</i> = 0.017). Furthermore, the disease-free survival for patients with a CPS ≥ 5 for PD1 was longer (153.7 months (95% confidence interval (CI): 134–173.6) vs. 98.6 months (95% confidence interval (CI): 83–114); <i>p</i> = 0.036). Additionally, a PD1 CPS ≥ 5 showed a better overall survival but the result was not statistically significant. No difference in survival was found between patients with PD-L1 higher or lower than CPS 5.</p><h3>Conclusion</h3><p>In this study we pointed out that there are significant clinical differences among several immunohistochemical scoring systems. In our trial, a PD1-positivity with CPS ≥ 5 and IC ≥ 1 were significantly associated to a better disease-free survival while there was no association with TPS. The PD1-IC scoring was associated with MMRd while the TPS scoring was not. Therefore, PD1-IC could be more appropriate for endometrial carcinomas compared to TPS and could also add prognostic information beside the more established PD-L1-staining. Further prospective studies are needed for a validation of these scores in combination with other biomarkers.</p></div>","PeriodicalId":8330,"journal":{"name":"Archives of Gynecology and Obstetrics","volume":"311 5","pages":"1395 - 1405"},"PeriodicalIF":2.1000,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00404-024-07862-y.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Gynecology and Obstetrics","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s00404-024-07862-y","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"OBSTETRICS & GYNECOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Introduction

PD1/PD-L1 inhibition (ICi) has recently become a new standard of care for patients with advanced MMR-deficient (MMRd) endometrial cancers. Nevertheless, response to immunotherapy is more complex than the presence of a single biomarker and therefore it remains challenging to predict patients response to ICi beyond MMRd tumors. Elevated PD-L1 expression (CPS ≥ 1) is often used as a prognostic marker as well as a predictive biomarker of response to ICi in different tumor types. In a retrospective, patient derived study, we analyzed PD1- and PD-L1 staining and correlated the results of different scores to clinical data to evaluate the prognostic impact of these scores.

Materials and methods

Immunohistochemical analysis of the receptor PD1 and the receptor ligand PD-L1 were performed on TMAs of primary paraffin‑embedded tumor samples. All patients were treated for primary endometrial cancer in the Department of Gynecology and Obstetrics, University Medical Center Schleswig–Holstein, Campus-Lübeck, Germany between the years 2006–2018. The evaluation and determination of the tumor proportion scoring (TPS), the combined positive score (CPS) and the immune cell scoring (IC) was automatically assessed semi-quantitatively, and results were correlated with clinicopathological characteristics and survival.

Results

130 samples were evaluable and 64% showed a positivity (IC > 0) for the receptor PD1 and 56% for the receptor ligand PD-L1. Patients with a PD1 IC Score ≥ 1 showed a significant longer disease-free survival of 140 months (95% confidence interval (CI): 124–158) compared to patients with a lower IC < 1 for PD1 of 89 months (95% confidence interval (CI): 69–110); p = 0.017). Furthermore, the disease-free survival for patients with a CPS ≥ 5 for PD1 was longer (153.7 months (95% confidence interval (CI): 134–173.6) vs. 98.6 months (95% confidence interval (CI): 83–114); p = 0.036). Additionally, a PD1 CPS ≥ 5 showed a better overall survival but the result was not statistically significant. No difference in survival was found between patients with PD-L1 higher or lower than CPS 5.

Conclusion

In this study we pointed out that there are significant clinical differences among several immunohistochemical scoring systems. In our trial, a PD1-positivity with CPS ≥ 5 and IC ≥ 1 were significantly associated to a better disease-free survival while there was no association with TPS. The PD1-IC scoring was associated with MMRd while the TPS scoring was not. Therefore, PD1-IC could be more appropriate for endometrial carcinomas compared to TPS and could also add prognostic information beside the more established PD-L1-staining. Further prospective studies are needed for a validation of these scores in combination with other biomarkers.

子宫内膜癌患者pd - 1和PD-L1免疫组化评分的预后和临床异质性。
PD1/PD-L1抑制(ICi)最近成为晚期mmr缺陷(MMRd)子宫内膜癌患者治疗的新标准。然而,对免疫治疗的反应比单一生物标志物的存在更为复杂,因此预测患者对MMRd肿瘤以外的ICi的反应仍然具有挑战性。PD-L1表达升高(CPS≥1)通常被用作不同肿瘤类型对ICi反应的预后标志物和预测性生物标志物。在一项来自患者的回顾性研究中,我们分析了PD1-和PD-L1染色,并将不同评分的结果与临床数据相关联,以评估这些评分对预后的影响。材料和方法:对原代石蜡包埋肿瘤样本的tma进行受体PD1和受体配体PD-L1的免疫组化分析。所有患者均于2006-2018年间在德国campus - l贝克石勒苏益格-荷尔斯泰因大学医学中心妇产科接受原发性子宫内膜癌治疗。肿瘤比例评分(TPS)、联合阳性评分(CPS)和免疫细胞评分(IC)的评估和确定采用半定量自动评估,结果与临床病理特征和生存率相关。结果:130个样本可评估,64%的样本显示受体PD1阳性(IC >), 56%的样本显示受体配体PD-L1阳性。PD1 IC评分≥1的患者与IC评分较低的患者相比,无病生存期明显延长,为140个月(95%可信区间(CI): 124-158)。结论:在本研究中,我们指出几种免疫组织化学评分系统之间存在显著的临床差异。在我们的试验中,CPS≥5和IC≥1的pd1阳性与更好的无病生存期显著相关,而与TPS无关。PD1-IC评分与MMRd相关,而TPS评分与MMRd无关。因此,与TPS相比,PD1-IC可能更适合于子宫内膜癌,并且除了更成熟的pd - l1染色外,还可以增加预后信息。需要进一步的前瞻性研究来验证这些评分与其他生物标志物的结合。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
4.70
自引率
15.40%
发文量
493
审稿时长
1 months
期刊介绍: Founded in 1870 as "Archiv für Gynaekologie", Archives of Gynecology and Obstetrics has a long and outstanding tradition. Since 1922 the journal has been the Organ of the Deutsche Gesellschaft für Gynäkologie und Geburtshilfe. "The Archives of Gynecology and Obstetrics" is circulated in over 40 countries world wide and is indexed in "PubMed/Medline" and "Science Citation Index Expanded/Journal Citation Report". The journal publishes invited and submitted reviews; peer-reviewed original articles about clinical topics and basic research as well as news and views and guidelines and position statements from all sub-specialties in gynecology and obstetrics.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信