U1016 Institut Cochin, INSERM, CARPEM, Paris, Île-de-France, France.
Université Paris Descartes, Sorbonne Paris Cité, Paris, Île-de-France, France.
Int J Gynecol Cancer. 2020 May;30(5):640-647. doi: 10.1136/ijgc-2019-000871. Epub 2020 Mar 12.
Molecular classification of endometrial carcinoma has been proposed to predict survival. However, its role in patient management remains to be determined. We aimed to identify whether a molecular and immunohistochemical classification of endometrial carcinoma could improve decision-making for adjuvant therapy.
All consecutive patients treated for endometrial carcinoma between 2010 and 2017 at Cochin University Hospital were included. Clinical risk of relapse was based on European Society for Medical Oncology-European Society of Gynaecological Oncology-European SocieTy for Radiotherapy & Oncology (ESMO-ESGO-ESTRO) consensus. The clinical event of interest was event-free survival. Formalin-fixed paraffin-embedded tissue samples were processed for histopathological analysis and DNA extraction. The nuclear expression of mismatch repair and TP53 proteins was analyzed by immunohistochemistry. Next-generation sequencing of a panel of 15 genes including and was performed using Ampliseq panels on Ion Torrent PGM (ThermoFisher). Tumors were allocated into four molecular groups using a sequential method based on next-generation sequencing and immunohistochemistry data: (1) /ultramutated-like; (2) MSI/hypermutated-like (mismatch repair-deficient); (3) -mutated (without mutations or mismatch repair deficiency); (4) not otherwise specified (the remaining tumors).
159 patients were included; 125 tumors were available for molecular characterization and distributed as follows: (1) /ultramutated-like: n=4 (3%); (2) MSI/hypermutated-like: n=35 (30%); (3) -mutated: n=30 (25%); and (4) not otherwise specified: n=49 (42%). Assessing the TP53 status by immunohistochemistry only rather than next-generation sequencing would have misclassified 6 tumors (5%). -mutated tumors were associated with poor prognosis, independently of International Federation of Gynecology and Obstetrics (FIGO) stage and histological grade (Cox-based adjusted hazard ratio (aHR) 5.54, 95% CI 2.30 to 13.4), and independently of clinical risk of relapse (aHR 3.92, 95% CI 1.59 to 9.64). Among patients with FIGO stage I-II tumors, 6 (38%) -mutated tumors had low/intermediate clinical risk of relapse and did not receive adjuvant chemotherapy or radiotherapy.
Endometrial carcinoma molecular classification identified potentially under-treated patients with poor molecular prognosis despite being at low/intermediate clinical risk of relapse. Consideration of molecular classification in adjuvant therapeutic decisions should be evaluated in prospective trials.
子宫内膜癌的分子分类已被提出用于预测生存。然而，其在患者管理中的作用仍有待确定。我们旨在确定子宫内膜癌的分子和免疫组织化学分类是否可以改善辅助治疗的决策。
纳入 2010 年至 2017 年在 Cochin 大学医院接受治疗的所有连续子宫内膜癌患者。复发的临床风险基于欧洲医学肿瘤学会-欧洲妇科肿瘤学会-欧洲放射治疗与肿瘤学会（ESMO-ESGO-ESTRO）共识。感兴趣的临床事件是无事件生存。福尔马林固定石蜡包埋组织样本用于进行组织病理学分析和 DNA 提取。通过免疫组织化学分析错配修复和 TP53 蛋白的核表达。使用 Ion Torrent PGM（ThermoFisher）上的 Ampliseq 试剂盒对包括 和 在内的 15 个基因的 panel 进行下一代测序。使用基于下一代测序和免疫组织化学数据的序贯方法将肿瘤分为四个分子组：（1） /超突变样；（2）MSI/高突变样（错配修复缺陷）；（3）-突变（无 突变或错配修复缺陷）；（4）未另作说明（其余肿瘤）。
纳入 159 例患者；125 例肿瘤可进行分子特征分析，分布如下：（1） /超突变样：n=4（3%）；（2）MSI/高突变样：n=35（30%）；（3）-突变：n=30（25%）；和（4）未另作说明：n=49（42%）。仅通过免疫组织化学而非下一代测序评估 TP53 状态会错误分类 6 个肿瘤（5%）。-突变肿瘤与预后不良独立相关，与国际妇产科联合会（FIGO）分期和组织学分级无关（基于 Cox 的调整危险比（aHR）5.54，95%CI 2.30 至 13.4），并且与临床复发风险无关（aHR 3.92，95%CI 1.59 至 9.64）。在 FIGO 分期 I-II 肿瘤患者中，6（38%）-突变肿瘤具有低/中临床复发风险，未接受辅助化疗或放疗。
尽管子宫内膜癌的分子分类处于低/中临床复发风险，但仍确定了具有不良分子预后的潜在治疗不足的患者。应在前瞻性试验中评估辅助治疗决策中考虑分子分类。
