[Fertility-preserving treatment outcomes in endometrial cancer and atypical hyperplasia patients with different molecular profiles].
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Objective: To investigate the impact of molecular classification and key oncogenes on the oncologic outcomes in patients with endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) receiving fertility-preserving treatment. Methods: Patients with EC and AEH undergoing progestin-based fertility-preserving treatment and receiving molecular classification as well as key oncogenes test at Obstetrics and Gynecology Hospital, Fudan University from January 2021 to March 2023 were reviewed. Hysteroscopic lesion resection and endometrial biopsy were performed before initiating hormone therapy and every 3 months during the treatment to evaluate the efficacy. The risk factors which had impact on the treatment outcomes in EC and AEH patients were further analyzed. Results: Of the 171 patients analyzed, the median age was 32 years, including 86 patients with EC and 85 patients with AEH. The distribution of molecular classification was as follows: 157 cases (91.8%) were classified as having no specific molecular profile (NSMP); 9 cases (5.3%), mismatch repair deficient (MMR-d); 3 cases (1.8%), POLE-mutated; 2 cases (1.2%), p53 abnormal. No difference was found in the cumulative 40-week complete response (CR) rate between the patients having NSMP or MMR-d (61.6% vs 60.0%; P=0.593), while the patients having MMR-d had increased risk than those having NSMP to have recurrence after CR (50.0% vs 14.4%; P=0.005). Multi-variant analysis showed PTEN gene multi-loci mutation (HR=0.413, 95%CI: 0.259-0.658; P<0.001) and PIK3CA gene mutation (HR=0.499, 95%CI: 0.310-0.804; P=0.004) were associated with a lower cumulative 40-week CR rate, and progestin-insensitivity (HR=3.825, 95%CI: 1.570-9.317; P=0.003) and MMR-d (HR=9.014, 95%CI: 1.734-46.873; P=0.009) were independent risk factors of recurrence in EC and AEH patients. Conclusions: No difference in cumulative 40-week CR rate is found in the patients having NSMP or MMR-d who received progestin-based fertility-preserving treatment, where the use of hysteroscopy during the treatment might be the reason, while those having MMR-d have a higher risk of recurrence after CR. Oncogene mutation of PTEN or PIK3CA gene might be associated with a lower response to progestin treatment. The molecular profiles help predict the fertility-preserving treatment outcomes in EC and AEH patients.目的： 探讨分子分型及关键致癌基因突变对子宫内膜癌（EC）和子宫内膜非典型增生（AEH）患者保留生育功能治疗结局的影响。 方法： 收集2021年1月至2023年3月在复旦大学附属妇产科医院接受高效孕激素保留生育功能治疗并进行分子分型及关键致癌基因检测的171例EC和AEH患者进行回顾性分析；所有患者在开始孕激素治疗前及治疗后约每3个月进行1次宫腔镜病灶切除及子宫内膜活检病理检查，用于评估疗效；进一步对影响EC和AEH患者治疗结局的相关因素进行分析。 结果： 171例EC和AEH患者的中位年龄为32岁；EC 86例，AEH 85例；分子分型：无特殊分子改变（NSMP）型157例（91.8%），错配修复缺陷（MMR-d）型9例（5.3%），POLE突变型3例（1.8%），p53异常型2例（1.2%）。NSMP型与MMR-d型患者治疗40周累积完全缓解（CR）率比较，差异无统计学意义（分别为61.6%、60.0%；P=0.593）；但与NSMP型患者相比，MMR-d型患者CR后的1年累积复发率显著升高（分别为14.4%、50.0%；P=0.015）。多因素分析显示，子宫内膜病变组织中存在PTEN基因多个位点突变（HR=0.413，95%CI为0.259~0.658；P<0.001）、PIK3CA基因突变（HR=0.499，95%CI为0.310~0.804；P=0.004）均为影响40周累积CR率的独立危险因素，难治性（HR=3.825，95%CI为1.570~9.317；P=0.003）和MMR-d型（HR=9.014，95%CI为1.734~46.873；P=0.009）均为影响EC和AEH患者复发的独立危险因素。 结论： 在采用高效孕激素保留生育功能治疗的EC和AEH患者中，分子分型为NSMP型与MMR-d型患者的40周累积CR率比较无显著差异，可能与患者均接受宫腔镜评估有关；但MMR-d型患者CR后的复发风险更高。PTEN或PIK3CA基因突变可能与子宫内膜病变组织更低的孕激素反应有关。分子特征有助于预测EC和AEH患者孕激素保留生育功能治疗的疗效。.Keywords:
Endometrial biopsy
Lynch Syndrome
Lynch Syndrome
Cancer syndrome
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Lynch Syndrome
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Objective: To explore the expression of PTEN and MTA1 and their correlation in the endometrial cancer.Methods: In 130 cases of endometrial cancer and 40 cases of normal endometrial,the expression of PTEN and MTA1 was examined with immunohis-tochemistry SP method and their correlation.Results: The expression of PTEN and MTA1 in endometrial cancer was higher than that in normal endometrial.(P0.01).PTEN expression levels in endometrial cancer were inversely correlated with MTA1 protein.(r=-0.35,P0.05).Conclusion: Expression of PTEN expression and MTA1 is inversely correlated with the development and progression of en-dometrial cancer.
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Background Approximately 2% to 5% of endometrial cancers may be due to an inherited susceptibility. Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, an autosomal-dominant inherited cancer susceptibility syndrome caused by a germline mutation in one of the DNA mismatch repair genes, accounts for the majority of inherited cases. Lynch syndrome is associated with early onset of cancer and the development of multiple cancer types, particularly colon and endometrial cancer. Methods The current status of knowledge regarding Lynch syndrome-associated endometrial cancer and methods for diagnosis, screening, and prevention of cancers is reviewed. Results The lifetime cumulative risk of endometrial cancer for women with Lynch syndrome is 40% to 60%, which equals or exceeds their risk of colorectal cancer. No current evidence suggests either a survival advantage or disadvantage to endometrial cancer that is associated with Lynch syndrome when these cases are compared with sporadic cases. A combination of family and personal medical history and tumor testing provides an efficient basis for diagnosing Lynch syndrome in women with endometrial cancer. Current gynecologic cancer screening guidelines for women with Lynch syndrome include annual endometrial sampling and transvaginal ultrasonography beginning at age 30 to 35 years. Conclusions Diagnosing endometrial cancer patients with Lynch syndrome has important clinical implications for the individual and family members. Screening and prevention practices can decrease the likelihood of developing additional cancers.
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<div>Abstract<p>Lynch syndrome is one of the most common hereditary cancer syndromes. Although Lynch syndrome is associated with increased risk for developing colorectal, endometrial, and other cancers specialized screening, risk-reducing surgery, and chemoprevention offer promise for reducing morbidity and mortality. Frequent colonoscopic surveillance has proven effective for early detection and prevention of Lynch syndrome-associated colorectal cancer; however, the optimal strategy for managing endometrial cancer risks in women with germline mutations in DNA mismatch repair genes has yet to be determined. In this issue of <i>Cancer Prevention Research</i>, Lu and colleagues report their findings of a phase II prospective, multicenter randomized trial comparing the effects of oral contraceptive pills and Depo-Provera on endometrial proliferation in women with Lynch syndrome. Although short-term hormonal treatment with either modality altered endometrial proliferation indices, it remains unknown whether hormonal suppression actually reduces endometrial cancer risk in women with Lynch syndrome. This trial represents the first of its kind in evaluating agents which might offer protection against Lynch syndrome-associated endometrial cancer and provides preliminary data regarding potential biomarkers for early detection of endometrial neoplasia. The investigators' experience with this trial also offers insights regarding the various technical and scientific challenges inherent in chemoprevention research. <i>Cancer Prev Res; 6(8); 755–9. ©2013 AACR</i>.</p></div>
Lynch Syndrome
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Lynch Syndrome
Uterine cancer
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Lynch Syndrome
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Women with Lynch syndrome have a risk up to 40-60% of developing endometrial cancer, which is higher than their risk of developing colorectal or ovarian cancer. To date, no data on the outcomes of patients with Lynch syndrome diagnosed with non-endometrioid endometrial cancer are available. The goal of this study was to evaluate the outcome of patients with Lynch syndrome diagnosed with non-endometrioid endometrial cancer.Data from consecutive patients diagnosed with Lynch syndrome and with a histological diagnosis of non-endometrioid endometrial cancer were retrospectively collected in two referral institutes in Italy. A case-control comparison (applying a propensity matching algorithm) was performed in order to compare patients with proven Lynch syndrome and controls. Inclusion criteria were: (a) histologically-proven endometrial cancer; (b) detection of a germline pathogenic variant in one of the MMR genes; (c) adequate follow-up. Only carriers of pathogenic or likely pathogenic variants (ie, class 5 and 4 according to the InSiGHT classification) were included in the study. Survival outcomes were assessed using KaplanMeier and Cox models.Overall, 137 patients with Lynch syndrome were collected. Mean patient age was 49.2 (10.9) years. Genes involved in the Lynch syndrome included MLH1, MSH2, and MSH6 in 43%, 39%, and 18% of cases, respectively. The study population included 27 patients with non-endometrioid endometrial cancer, who were matched 1:2 with patients with sporadic cancers using a propensity matching algorithm. After a median follow-up of 134 months (range 1-295), 2 (7.4%) of the 27 patients developed recurrent disease (3 and 36 months) and subsequently died of disease (7 and 91 months). Patients diagnosed with Lynch syndrome experienced better disease-free survival (HR 7.86 (95% CI 1.79 to 34.5); p=0.006) and overall survival (HR 5.33 (95% CI 1.18 to 23.9); p=0.029) than controls.Non-endometrioid endometrial cancer occurring in patients with Lynch syndrome might be associated with improved oncologic outcomes compared with controls. Genetic/molecular profiling should be investigated in order to better understand the mechanism underlying the prognosis.
Lynch Syndrome
MSH6
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Lynch syndrome is one of the most common hereditary cancer syndromes. Although Lynch syndrome is associated with increased risk for developing colorectal, endometrial, and other cancers specialized screening, risk-reducing surgery, and chemoprevention offer promise for reducing morbidity and mortality. Frequent colonoscopic surveillance has proven effective for early detection and prevention of Lynch syndrome-associated colorectal cancer; however, the optimal strategy for managing endometrial cancer risks in women with germline mutations in DNA mismatch repair genes has yet to be determined. In this issue of Cancer Prevention Research, Lu and colleagues report their findings of a phase II prospective, multicenter randomized trial comparing the effects of oral contraceptive pills and Depo-Provera on endometrial proliferation in women with Lynch syndrome. Although short-term hormonal treatment with either modality altered endometrial proliferation indices, it remains unknown whether hormonal suppression actually reduces endometrial cancer risk in women with Lynch syndrome. This trial represents the first of its kind in evaluating agents which might offer protection against Lynch syndrome-associated endometrial cancer and provides preliminary data regarding potential biomarkers for early detection of endometrial neoplasia. The investigators' experience with this trial also offers insights regarding the various technical and scientific challenges inherent in chemoprevention research.
Lynch Syndrome
Cancer Prevention
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