目的:本研究旨在评估子宫内膜不典型增生(EAH)患者行保留生育治疗后错配修复缺陷(MMR-d)和p53异常表达(p53abn)的预后能力。
方法:这项回顾性研究评估了51例接受保留生育力治疗的EAH患者。收集激素治疗前获得的子宫内膜活检标本,并用于MMR和p53蛋白的免疫组织化学染色。回应,复发,根据年龄评估进展率,身体质量指数,糖尿病,多囊卵巢综合征,生殖史,MMR状态,和p53状态。
结果:总体而言,11/51(21.6%)患者MMR蛋白缺失,6/51(11.8%)患者p53abn缺失。初始治疗后12个月,MMR-d患者的完全反应(CR)率低于正常染色患者(p=0.049)。在达到CR后的1年随访中,MMR-d患者的复发率明显高于MMR-p患者(p=0.035)。此外,MMR-d患者在保留生育功能治疗后2年,3年和4年的疾病进展发生率较高(分别为p=0.001,p=0.01和p=0.035).在达到CR后的1年和2年随访中,p53abn患者的复发率高于p53wt患者(分别为p=0.047和p=0.036)。此外,p53abn患者在保留生育功能治疗后3年和4年的疾病进展发生率较高(分别为p=0.02和p=0.049).
结论:患有MMR-d和p53abn的EAH患者疾病复发和进展的风险显著增高。因此,MMR-d和p53abn可用作EAH中孕激素抵抗和子宫内膜肿瘤发生的预测生物标志物。
This study aimed to evaluate the prognostic ability of mismatch repair deficiency (MMR-d) and abnormal p53 expression (p53abn) in patients with endometrial atypical hyperplasia (EAH) who underwent fertility-preserving treatment.
This retrospective study evaluated 51 patients with EAH who underwent fertility-sparing treatment. Endometrial biopsy specimens obtained before hormone therapy were collected and used for immunohistochemical staining for MMR and p53 proteins. Response, relapse, and progression rates were assessed based on age, body mass index, diabetes, polycystic ovary syndrome, reproductive history, MMR status, and p53 status.
Overall, 11/51 (21.6%) patients had loss of MMR proteins and 6/51 (11.8%) had p53abn. Patients with MMR-d had lower complete response (CR) rates than those with normal staining patients at 12 months after initial treatment (p = 0.049). Patients with MMR-d had significantly higher relapse rates than those with MMR-p at the 1-year follow-ups after achieving CR (p = 0.035). Moreover, patients with MMR-d had a higher incidence of disease progression at 2, 3, and 4 years after fertility-sparing treatment (p = 0.001, p = 0.01 and p = 0.035, respectively). Patients with p53abn had higher relapse rates than those with p53wt at the 1- and 2-year follow-ups after achieving CR (p = 0.047 and p = 0.036, respectively). Moreover, patients with p53abn had a higher incidence of disease progression at 3 and 4 years after fertility-sparing treatment (p = 0.02 and p = 0.049, respectively).
EAH patients with MMR-d and p53abn have a significantly higher risk of disease relapse and progression. Thus, MMR-d and p53abn may be used as predictive biomarkers of progestin resistance and endometrial tumorigenesis in EAH.