Mismatch repair status influences response to fertility-sparing treatment of endometrial cancer
Mismatch repair status influences response to fertility-sparing treatment of endometrial cancer
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DOI：
10.1016/j.ajog.2020.10.003
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发表时间：
2021-03-26
影响因子：
9.8
通讯作者：
Kim, Young Tae
中科院分区：
文献类型：
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作者：
Chung, Young Shin;Woo, Ha Young;Kim, Young Tae
背景：年龄小于40岁的患者通常表现为早期子宫内膜癌，预后良好。然而，这些患者通常处于育龄期，可能需要保留生育能力的选择。生物标志物的鉴定可能会改善这些患者的临床结局，并有助于生育保留管理;然而，迄今为止还没有关于生物标志物分析的报道。目的：本研究旨在评估子宫内膜癌前摄分子风险分类器在子宫内膜癌生育保留管理中的预后意义。共对57例激素治疗前获得的子宫内膜活检标本进行了评估，并根据子宫内膜癌分子亚型的主动分子风险分类器对患者进行了分类（错配修复缺陷、DNA聚合酶突变、野生型p53和异常p53）。主要终点是激素治疗后的反应率。次要终点是完全缓解后的复发率、治疗失败的子宫切除率和子宫切除术后的分期诊断率。结果：57例患者中，9例（15.8%）存在错配修复缺陷，2例（3.5%）存在DNA聚合酶epsilon突变，45例（78.9%）存在野生型p53，1例（1.8%）存在异常p53。总体而言，激素治疗后的完全缓解率为75.4%。就最佳总体缓解而言，错配修复缺陷患者的完全缓解或部分缓解率显著低于野生型p53患者（44.4% [95%可信区间，4.0-85.0] vs 82.2% [95%可信区间，71.0-94.0]; P= 0.018）和6个月时的完全缓解率（11.1% [95%置信区间，0.2-37.0] vs 53.3% [95%置信区间，38.0-68.0]; P= 0.010）。在错配修复缺陷的患者中，4例因治疗失败而接受了立即子宫切除术，3例在子宫切除术后出现了前期诊断。结论：子宫内膜癌的主动分子风险分类分子分类在子宫内膜癌的生育保留管理中具有预后意义，从而使早期分层和风险分配直接护理。错配修复状态可以作为一种预测性生物标志物，用于选择可能受益于激素治疗的患者。这些发现需要在更大规模的研究中得到验证。
BACKGROUND: Patients younger than 40 years usually present with early-stage endometrial cancer with favorable prognosis. However, such patients are usually in their childbearing age and may desire fertility-sparing options. The identification of biomarkers may improve the clinical outcomes in these patients and aid in fertility-sparing management; however, there has been no reports on biomarker analysis so far.OBJECTIVE: This study aimed to evaluate the prognostic significance of Proactive Molecular Risk Classifier for Endometrial Cancer in the fertility-sparing management of endometrial cancer.STUDY DESIGN: A total of 57 endometrial biopsy specimens obtained before hormone therapy were evaluated, and patients were classified according to the Proactive Molecular Risk Classifier for Endometrial Cancer molecular subtypes (mismatch repair deficiency, DNA polymerase epsilon mutation, wild-type p53, and abnormal p53). The primary endpoint was the response rate after hormone therapy. The secondary endpoint was the recurrence rate after the complete response, hysterectomy rate owing to treatment failure, and upstaged diagnosis rate after hysterectomy.RESULTS: Of 57 patients, 9 (15.8%) had mismatch repair deficiency, 2 (3.5%) had DNA polymerase epsilon mutation, 45 (78.9%) had wild-type p53, and 1 (1.8%) had abnormal p53. Overall, the complete response rate was 75.4% after hormone therapy. Patients with mismatch repair deficiency had a significantly lower complete response or partial response rate than those with wild-type p53 in terms of the best overall response (44.4% [95% confidence interval, 4.0-85.0] vs 82.2% [95% confidence interval, 71.0-94.0]; P=.018) and complete response rate at 6 months (11.1% [95% confidence interval, 0.2-37.0] vs 53.3% [95% confidence interval, 38.0-68.0]; P=.010). Among patients with mismatch repair deficiency, 4 underwent immediate hysterectomy because of treatment failure and 3 presented upstaged diagnosis after hysterectomy.CONCLUSION: The Proactive Molecular Risk Classifier for Endometrial Cancer molecular classification has prognostic significance in the fertility-sparing management of endometrial cancer, thereby enabling early stratification and risk assignment to direct care. Mismatch repair status could be used as a predictive biomarker for selecting patients who could benefit from hormone therapy. These findings need to be validated in larger studies.