Department of Biochemistry, Penn State College of Medicine, Penn State Health, Hershey, Pennsylvania.
Institute for Personalized Medicine, Penn State College of Medicine, Penn State Health, Hershey, Pennsylvania.
Cancer. 2020 Jun 15;126(12):2775-2783. doi: 10.1002/cncr.32822. Epub 2020 Mar 18.
Endometrial hyperplasia is a precursor to endometrioid adenocarcinoma (EMC), the most common uterine cancer. The likelihood of progression to carcinoma may be evaluated by histologic subclassification of endometrial hyperplasia, although these subclasses are subjective and only modestly reproducible among pathologists. Patient care would be improved by a more objective test to predict the risk of cancer progression.
Next-generation sequencing was performed on archived endometrial biopsy specimens from a retrospective cohort of women with endometrial hyperplasia. Cases were considered to be either progressing if the patient subsequently developed EMC or resolving if the patient had a subsequent negative tissue sampling or no cancer during medium-term follow-up (32 patients: 15 progressing and 17 resolving). Somatic mutations in endometrial hyperplasia were assessed for enrichment in progressing cases versus resolving cases, with an emphasis on genes commonly mutated in EMC.
Several mutations were more common in progressing hyperplasia than resolving hyperplasia, although significant overlap was observed between progressing and resolving cases. Mutations included those in PTEN, PIK3CA, and FGFR2, genes commonly mutated in EMC. Mutations in ARID1A and MYC were seen only in progressing hyperplasia, although these were uncommon; this limited diagnostic sensitivity. Progressing hyperplasia demonstrated an accumulation of mutations in oncogenic signaling pathways similarly to endometrial carcinoma.
Because of mutational differences between progressing and nonprogressing hyperplasia, mutational analysis may predict the risk of progression from endometrial hyperplasia to EMC.
子宫内膜增生是子宫内膜样腺癌（EMC）的前身，EMC 是最常见的子宫癌。子宫内膜增生的组织学亚分类可以评估进展为癌的可能性，尽管这些亚类在病理学家中是主观的，并且只是适度可重复的。如果有一种更客观的测试来预测癌症进展的风险，将会改善患者的护理。
对来自子宫内膜增生回顾性队列的存档子宫内膜活检标本进行了下一代测序。如果患者随后发展为 EMC，则认为病例进展，如果患者随后的组织取样为阴性或在中期随访（32 例患者：15 例进展和 17 例缓解）期间没有癌症，则认为病例缓解。评估了子宫内膜增生中的体细胞突变在进展病例与缓解病例中的富集情况，重点是 EMC 中常见的突变基因。
与缓解性增生相比，进展性增生中存在几种更常见的突变，尽管在进展性和缓解性病例之间观察到明显的重叠。突变包括 PTEN、PIK3CA 和 FGFR2 等基因的突变，这些基因在 EMC 中经常发生突变。ARID1A 和 MYC 的突变仅在进展性增生中可见，尽管这些突变并不常见；这限制了诊断的敏感性。进展性增生表现出与子宫内膜癌相似的致癌信号通路中突变的积累。
由于进展性和非进展性增生之间存在突变差异，因此突变分析可能可以预测从子宫内膜增生到 EMC 的进展风险。
