Table2_Molecular Evaluation of Endometrial Dedifferentiated Carcinoma, Endometrioid Carcinoma, Carcinosarcoma, and Serous Carcinoma Using a Custom-Made Small Cancer Panel.XLSX

It is often difficult to histologically differentiate among endometrial dedifferentiated carcinoma (DC), endometrioid carcinoma (EC), serous carcinoma (SC), and carcinosarcoma (CS) due to the presence of solid components. In this study, we aimed to categorize these carcinomas according to The Cancer Genome Atlas (TCGA) classification using a small custom-made cancer genome panel (56 genes and 17 microsatellite regions) for integrated molecular diagnosis. A total of 36 endometrial cancer cases with solid components were assessed using IHC, next-generation sequencing (NGS), and the custom-made panel. Among 19 EC cases, six were categorized as MMR-deficient (MMR-d) and eight were classified as having a nonspecific molecular profile. Three EC cases were classified as POLE mutation (POLEmut)-type, which had a very high tumor mutation burden (TMB) and low microsatellite instability (MSI). Increased TMB and MSI were observed in all three DC cases, classified as MMR-d with mutations in MLH1 and POLD1. Except for one case classified as MMR-d, all SC cases exhibited TP53 mutations and were classified as p53 mutation-type. SC cases also exhibited amplification of CCND1, CCNE1, and MYC. CS cases were classified as three TCGA types other than the POLEmut-type. The IHC results for p53 and ARID1A were almost consistent with their mutation status. NGS analysis using a small panel enables categorization of endometrial cancers with solid proliferation according to TCGA classification. As TCGA molecular classification does not consider histological findings, an integrated analytical procedure including IHC and NGS may be a practical diagnostic tool for endometrial cancers.

由于存在实性成分，子宫内膜去分化癌（endometrial dedifferentiated carcinoma, DC）、子宫内膜样癌（endometrioid carcinoma, EC）、浆液性癌（serous carcinoma, SC）与癌肉瘤（carcinosarcoma, CS）的组织学鉴别往往较为困难。本研究旨在利用一款定制小型癌症基因组检测面板（涵盖56个基因与17个微卫星区域）开展整合分子诊断，依据肿瘤基因组图谱（The Cancer Genome Atlas, TCGA）分类标准对上述癌种进行分型。本研究共纳入36例伴实性成分的子宫内膜癌病例，采用免疫组化（IHC）、下一代测序（NGS）及该定制检测面板进行评估。在19例EC病例中，6例被归类为错配修复缺陷（MMR-deficient, MMR-d）型，8例被划分为分子特征非特异性类型。3例EC病例被归类为POLE突变（POLEmut）型，此类病例具有极高的肿瘤突变负荷（TMB）与极低的微卫星不稳定（MSI）水平。3例DC病例均表现为TMB升高与MSI增高，且被归类为携带MLH1与POLD1突变的MMR-d型。除1例MMR-d型病例外，所有SC病例均存在TP53突变，被归类为p53突变型。SC病例同时存在CCND1、CCNE1及MYC基因扩增。CS病例被划分为POLEmut型以外的3种TCGA分子亚型。p53与ARID1A的IHC结果与其突变状态基本一致。采用小型检测面板开展的NGS分析，可依据TCGA分类标准对伴实性增殖成分的子宫内膜癌进行分型。由于TCGA分子分类未纳入组织学特征，结合IHC与NGS的整合分析流程有望成为子宫内膜癌实用的诊断工具。