Andrade Diocésio Alves Pinto, Bonatelli Murilo, de Paula Flávia Escremim, Berardinelli Gustavo Noriz, Teixeira Gustavo Ramos, Dos Reis Monise Tadin, Barbin Flávia Fazzio, Andrade Carlos Eduardo Mattos da Cunha, Aguiar Vinicius Pereira, Hermoza Alejandro Delfos, Hirai Welinton Yoshio, Schmidt Ronaldo Luís, Reis Rui Manuel, Dos Reis Ricardos
Oncoclínicas&CO, Medica Scientia Innovation Research (MEDSIR)/MedSir, Ribeirão Preto, São Paulo, Brazil.
Molecular Diagnostic Laboratory, Barretos Cancer Hospital, São Paulo, Brazil.
Front Oncol. 2024 Dec 13;14:1503901. doi: 10.3389/fonc.2024.1503901. eCollection 2024.
Molecular classification of endometrial cancer (EC) has emerged as a key approach to individualize therapy and define prognostic outcomes. This study aimed to implement the traditional ProMisE classification in a Brazilian population, compared with a molecular setting of ProMisE biomarkers, and evaluate its impact on patients' prognosis.
A prospective cohort of 114 patients with primary EC treated at Barretos Cancer Hospital (BCH) between October 2020 and December 2022 was conducted. Pathology diagnosis, staging, treatment, and follow-up data were collected. The traditional ProMisE methodology was carried out by hotspot sequencing and immunohistochemistry (IHC) for p53 and mismatch repair (MMR) proteins. We further evaluate the MMR and status by molecular approach, namely microsatellite instability (MSI) by PCR-based and mutation analysis by next-generation sequencing (NGS). The results of the 4 molecular groups in both methodologies were compared regarding agreement accuracy and survival outcomes.
Among the 114 cases, the traditional ProMisE groups were: mut 15.8%, MMRd 28.1%, p53abn 27.2%, and no specific molecular profile (NSMP) 28.9%. Considering the molecular classification approach, we observed a mut group , MSI group of 23.7%, mutation of 27.2%, and NSMP of 33.3%. The concordance rate of both approaches was 86.8% (99/114 cases) with an overall accuracy of 0.87. Importantly, both traditional and molecular ProMisE approaches were associated with significant distinct overall survival (OS) and progression-free survival (PFS) outcomes, with mut patients exhibiting a better prognosis (93.8% OS, at 24 months), whereas the p53abn having a worse survival time (68.9% of OS, at 24 months).
We reported for the first time the Brazilian profile of the ProMisE classification of endometrial cancer and demonstrated the prognostic impact of the traditional and molecular ProMisE classification on patient outcomes.
子宫内膜癌（EC）的分子分类已成为实现个体化治疗和确定预后结果的关键方法。本研究旨在在巴西人群中应用传统的ProMisE分类，与ProMisE生物标志物的分子背景进行比较，并评估其对患者预后的影响。
对2020年10月至2022年12月在巴雷托斯癌症医院（BCH）接受治疗的114例原发性EC患者进行前瞻性队列研究。收集病理诊断、分期、治疗及随访数据。传统的ProMisE方法通过热点测序和免疫组织化学（IHC）检测p53和错配修复（MMR）蛋白来进行。我们进一步通过分子方法评估MMR和状态，即基于聚合酶链反应（PCR）的微卫星不稳定性（MSI）和通过下一代测序（NGS）进行的突变分析。比较两种方法中4个分子组在一致性准确性和生存结果方面的情况。
在114例病例中，传统的ProMisE组分别为：突变型（mut）15.8%，错配修复缺陷型（MMRd）28.1%，p53异常型（p53abn）27.2%，无特定分子谱型（NSMP）28.9%。考虑分子分类方法，我们观察到突变型组、MSI组占23.7%、突变型占27.2%以及NSMP占33.3%。两种方法的一致性率为86.8%（99/114例），总体准确率为0.87。重要的是，传统和分子ProMisE方法均与显著不同的总生存期（OS）和无进展生存期（PFS）结果相关，突变型患者预后较好（24个月时OS为93.8%），而p53abn型患者生存时间较差（24个月时OS为68.9%）。
我们首次报告了巴西子宫内膜癌ProMisE分类的情况，并证明了传统和分子ProMisE分类对患者预后的影响。
