Department of Gynecology, Istituto Europeo di Oncologia, Milan, Italy.
Department of Obstetrics and Gynecology, Division of Gynecologic Surgery, Mayo Clinic, Rochester, Minnesota, USA.
Int J Gynecol Cancer. 2024 Feb 5;34(2):229-238. doi: 10.1136/ijgc-2023-004864.
Endometrial cancers with more than one molecular feature- mutations (POLEmut), mismatch repair protein deficiency (MMRd), p53 abnormality (p53abn)-are called 'multiple classifiers'.
To describe our cohort of multiple classifiers and to report the results of a review on their incidence and the techniques used to identify them.
Multiple classifiers identified at the European Institute of Oncology, Milan, between April 2019 and Decmber 2022, were included. Clinicopathological, molecular characteristics, and oncologic outcomes were summarized and compared between single and multiple classifiers sharing common features. Studies on molecular classification of endometrial cancer were searched in the PubMed Database to collect data on the incidence of multiple classifiers and the techniques used for classification.
Among 422 patients, 48 (11.4%) were multiple classifiers: 15 (3.6%) POLEmut-p53abn, 2 (0.5%) POLEmut-MMRd, 28 (6.6%) MMRd-p53abn, and 3 (0.7%) POLEmut-MMRd-p53abn. MMRd-p53abn and MMRd differed in histotype (non-endometrioid: 14.8% vs 2.0%, p=0.006), grade (high-grade: 55.6% vs 22.2%, p=0.001), and MMR proteins expression, whereas they differed from p53abn in histotype (non-endometrioid: 14.8% vs 50.0%, p=0.006). POLEmut-p53abn and POLEmut differed only in grade (high-grade: 66.7% vs 22.7%, p=0.008), while they differed from p53abn in age (56.1 vs 66.7 years, p=0.003), stage (advanced: 6.7% vs 53.4%, p=0.001), and histotype (non-endometrioid: 6.7% vs 50.0%, p=0.002). Two (7.1%) patients with MMRd-p53abn, 4 (4.0%) with MMRd, and 25 (34.3%) with p53abn had a recurrence. No recurrences were observed in POLEmut-p53abn and POLEmut. sequencing allowed the detection of additional 7 (18.9%) multiple classifiers with normal p53 immunostaining. The incidence of multiple classifiers ranged from 1.8% to 9.8% in 10 published studies including >100 patients. When only p53 immunohistochemistry was performed, the highest incidence was 3.9%.
The characteristics of POLEmut-p53abn resembled those of POLEmut, whereas MMRd-p53abn appeared to be intermediate between MMRd and p53abn. The high proportion of multiple classifiers may be related to the methods used for molecular classification, which included both p53 immunohistochemistry and sequencing.
具有多种分子特征的子宫内膜癌——突变（POLEmut）、错配修复蛋白缺陷（MMRd）、p53 异常（p53abn）——被称为“多分类器”。
描述我们的多分类器队列，并报告关于其发生率以及用于识别它们的技术的研究结果。
纳入 2019 年 4 月至 2022 年 12 月在米兰欧洲肿瘤研究所鉴定的多分类器。总结了临床病理、分子特征和肿瘤学结局，并比较了具有共同特征的单分类器和多分类器之间的结果。在 PubMed 数据库中搜索了关于子宫内膜癌分子分类的研究，以收集多分类器发生率和分类所用技术的数据。
在 422 名患者中，48 名（11.4%）为多分类器：15 名（3.6%）POLEmut-p53abn、2 名（0.5%）POLEmut-MMRd、28 名（6.6%）MMRd-p53abn 和 3 名（0.7%）POLEmut-MMRd-p53abn。MMRd-p53abn 和 MMRd 在组织学类型（非子宫内膜样：14.8% vs 2.0%，p=0.006）、分级（高级别：55.6% vs 22.2%，p=0.001）和 MMR 蛋白表达方面存在差异，而与 p53abn 的差异在于组织学类型（非子宫内膜样：14.8% vs 50.0%，p=0.006）。POLEmut-p53abn 和 POLEmut 仅在分级（高级别：66.7% vs 22.7%，p=0.008）方面存在差异，而与 p53abn 的差异在于年龄（56.1 岁 vs 66.7 岁，p=0.003）、分期（晚期：6.7% vs 53.4%，p=0.001）和组织学类型（非子宫内膜样：6.7% vs 50.0%，p=0.002）。2 名（7.1%）MMRd-p53abn 患者、4 名（4.0%）MMRd 患者和 25 名（34.3%）p53abn 患者出现复发。POLEmut-p53abn 和 POLEmut 未观察到复发。测序允许检测到另外 7 名（18.9%）具有正常 p53 免疫染色的多分类器。10 项包括>100 名患者的研究中，多分类器的发生率为 1.8%至 9.8%。当仅进行 p53 免疫组化检查时，最高发生率为 3.9%。
POLEmut-p53abn 的特征与 POLEmut 相似，而 MMRd-p53abn 似乎介于 MMRd 和 p53abn 之间。多分类器的高比例可能与用于分子分类的方法有关，该方法包括 p53 免疫组化和测序。
