转录因子在无特定分子谱（NSMP）亚型子宫内膜癌患者中的预后作用。

Prognostic role of transcription factor in patients with endometrial cancer of no specific molecular profile (NSMP) subtype.

机构信息

Department of Obstetrics and Gynecology, Division of General Gynecology and Gynecologic Oncology, Medical University of Vienna, Vienna, Austria.

Department of Pathology, Medical University of Vienna, Vienna, Austria.

出版信息

Int J Gynecol Cancer. 2024 Jun 3;34(6):840-846. doi: 10.1136/ijgc-2023-005111.

DOI:10.1136/ijgc-2023-005111

PMID:38508586

Abstract

OBJECTIVE

As more than 50% of newly diagnosed endometrial cancers remain classified as 'no specific molecular subtype' (NSMP) due to a lack of established biomarkers to further improve molecular subtyping, this study aims to evaluate the prognostic value of in endometrial cancers of NSMP subtype.

METHODS

Prospectively collected molecular profiling data of all consecutive patients with endometrial cancer who underwent primary surgery at our department between August 2017 and June 2022 and for whom both molecular profiling and clinical follow-up data were available were retrospectively evaluated. Tumor specimens were evaluated by combined mismatch repair protein immunohistochemistry and targeted next-generation hotspot sequencing. mutational status, as defined by full-length gene sequencing, was matched with risk of recurrence, progression-free and disease-specific survival within the NSMP cohort.

RESULTS

A total of 127 patients with endometrial cancer were included. Among 72 patients with tumors of NSMP subtype (56.7%), mutations were identified in 24 cases (33.3%). mutations were significantly associated with a higher risk of recurrence (37.5% vs 12.5%, OR 4.20, 95% CI 1.28 to 13.80, p=0.018) and impaired progression-free survival (HR 3.96, 95% CI 1.41 to 11.15, p=0.009), but not with disease-specific survival. The results for both risk of recurrence (OR 3.70, 95% CI 1.04 to 13.13, p=0.043) and progression-free survival (HR 3.19, 95% CI 1.10 to 9.25, p=0.033) were confirmed in multivariable analysis compared with advanced tumor stage International Federation of Gynecology and Obstetrics (2009) (FIGO ≥III) and impaired Eastern Clinical Oncology Group performance status (ECOG ≥1).

CONCLUSION

appears to identify patients with endometrial cancer of NSMP subtypes with a higher risk of recurrence and could be used as a future prognostic biomarker. After clinical validation, assessment could help to further sub-classify selected endometrial cancers and improve personalized treatment strategies.

摘要

目的

由于缺乏已确立的生物标志物来进一步改善分子分型，超过 50%的新诊断子宫内膜癌仍被归类为“无特定分子亚型”（NSMP）。本研究旨在评估在 NSMP 亚型子宫内膜癌中的预后价值。

方法

回顾性评估 2017 年 8 月至 2022 年 6 月期间在我院接受初次手术且具有分子谱分析和临床随访数据的连续患者的前瞻性收集的分子谱数据。通过联合错配修复蛋白免疫组化和靶向下一代热点测序评估肿瘤标本。根据全长基因测序定义的突变状态与 NSMP 队列中的复发风险、无进展生存期和疾病特异性生存期进行匹配。

结果

共纳入 127 例子宫内膜癌患者。在 72 例 NSMP 亚型肿瘤患者中（56.7%），24 例（33.3%）存在突变。突变与更高的复发风险（37.5%比 12.5%，OR 4.20，95%CI 1.28 至 13.80，p=0.018）和无进展生存期受损（HR 3.96，95%CI 1.41 至 11.15，p=0.009）显著相关，但与疾病特异性生存无关。在多变量分析中，与晚期国际妇产科联合会（2009 年）（FIGO ≥III）肿瘤分期和较差的东部临床肿瘤学组表现状态（ECOG ≥1）相比，复发风险（OR 3.70，95%CI 1.04 至 13.13，p=0.043）和无进展生存期（HR 3.19，95%CI 1.10 至 9.25，p=0.033）的结果均得到确认。