Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Stanford University School of Medicine, Stanford, CA, USA.
Histopathology. 2024 Oct;85(4):614-626. doi: 10.1111/his.15232. Epub 2024 Jun 11.
Molecular classification according to The Cancer Genome Atlas (TCGA) improves endometrial endometrioid carcinoma (EEC) prognostication and has specific treatment implications; however, original data were skewed towards low-grade and low-stage tumours. Herein, we molecularly classify EECs metastatic at the time of diagnosis or with subsequently documented recurrent/metastatic disease to examine correlation with clinical outcomes.
TCGA categories include POLE-mutated, microsatellite instability (MSI), p53 abnormal (p53 abnl) and no specific molecular profile (NSMP). POLE targeted sequencing at exons 9, 11, 13 and 14 and immunohistochemistry (IHC) for PMS2, MSH6 and p53 were performed to establish molecular classification.
The distribution in our cohort of 141 EECs was similar to that generally reported in EEC, with nine POLE-mutated (6%), 45 MSI (32%), 16 p53 abnl (11%) and 71 NSMP (50%), with similar distributions between low- and high-stage cohorts. We demonstrate that when stratified by molecular subtype, disease-specific survival from the time of high-stage (stages III-IV) presentation or time of recurrence in low-stage (stages I-II) disease among metastatic and/or recurrent EEC is strongly associated with TCGA classification (high-stage P = 0.02, low-stage P = 0.017). Discordant molecular classification between primary and metastatic/recurrent tumours occurred in four of 105 (3.8%) patients, two related to PMS2/MSH6 IHC and two related to p53 IHC.
We demonstrate that molecular classification is prognostically relevant not only at the time of diagnosis, but also at the time of recurrence and in the metastatic setting. Rare subclonal alterations occur and suggest a role for confirming TCGA classification in recurrent/metastatic tumours.
根据癌症基因组图谱 (TCGA) 进行分子分类可改善子宫内膜样癌 (EEC) 的预后，并具有特定的治疗意义；然而，原始数据偏向于低级别和低分期的肿瘤。在此，我们对诊断时转移性或随后有记录的复发性/转移性疾病的 EEC 进行分子分类，以检查与临床结局的相关性。
TCGA 类别包括 POLE 突变型、微卫星不稳定 (MSI)、p53 异常 (p53 abnl) 和无特定分子谱 (NSMP)。进行 POLE 靶向测序外显子 9、11、13 和 14 以及 PMS2、MSH6 和 p53 的免疫组化 (IHC) 以建立分子分类。
在我们的 141 例 EEC 队列中，分布与 EEC 通常报道的分布相似，其中 9 例 POLE 突变型 (6%)、45 例 MSI (32%)、16 例 p53 abnl (11%) 和 71 例 NSMP (50%)，低分期和高分期队列之间的分布相似。我们证明，当按分子亚型分层时，高分期 (III-IV 期) 表现时或低分期 (I-II 期) 疾病复发时的疾病特异性生存与 TCGA 分类密切相关 (高分期 P=0.02，低分期 P=0.017)。在 105 例中有 4 例 (3.8%) 患者的原发性和转移性/复发性肿瘤之间的分子分类不一致，其中 2 例与 PMS2/MSH6 IHC 相关，2 例与 p53 IHC 相关。
我们证明分子分类不仅在诊断时，而且在复发时和转移时都具有预后相关性。罕见的亚克隆改变发生，并提示在复发性/转移性肿瘤中确认 TCGA 分类的作用。
