Jiongbo Liao

Obstetrics and Gynecology Hospital of Fudan University

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Xiaojun Chen

Obstetrics and Gynecology Hospital of Fudan University

Wenyu Shao

Obstetrics and Gynecology Hospital of Fudan University

Zhiying Xu

Obstetrics and Gynecology Hospital of Fudan University

Weiwei Shan

Obstetrics and Gynecology Hospital of Fudan University

Chengcheng Ning

Obstetrics and Gynecology Hospital of Fudan University

Shuang Zhou

Chinese Academy of Medical Sciences & Peking Union Medical College

Qin Zhu

Obstetrics and Gynecology Hospital of Fudan University

Bingyi Yang

Obstetrics and Gynecology Hospital of Fudan University

Xuezhen Luo

Obstetrics and Gynecology Hospital of Fudan University

Jun Guan

Obstetrics and Gynecology Hospital of Fudan University

Cooperative Institutions

Obstetrics and Gynecology Hospital of Fudan University

Fudan University

Augusta University

Augusta University Health

Shanghai Medical College of Fudan University

Zhejiang University

Huazhong University of Science and Technology

Chinese Academy of Sciences

Ministry of Education of the People's Republic of China

Chinese University of Hong Kong

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Evaluation of Factors Influencing Lymph Node Metastasis in Grade 3 Endometrial Cancers: A Retrospective Study

Authorea (Authorea) (2020)

Bo Wang Qian Wang Yue Shi Wenyu Shao Jiongbo Liao

Objective: To evaluate the risk of lymph node metastasis and figure out necessity of lymphadenectomy in grade 3 endometroid endometrial cancer (EEC) patients. Methods: From 2009 to 2019, 3751 endometrial cancer (EC) patients were diagnosed at Gynecology Hospital of Fudan University, 1235 EEC patients were enrolled in multivariable analysis. 381 patients had survival analysis attributed to sufficient follow-up information. Kaplan-Meier curve and logrank test were used to analyze the survival rate. Results: Among 1235 EEC patients, multivariate analysis showed lymph-vascular invasion (LVSI), adnexal involvement (AI), cervical stroma involvement (CSI) were independent risk factors of lymph node metastasis (LNM) in grade 3 (G3) cohort (OR=3.45, 5.83, 8.93; 95% CI 1.12-10.64, 1.52-22.35, 2.85-28.00 respectively). LNM rates increased from 3.3% to 75% for EEC G3 cohort with the increase of risk factors from one to three. There were no differences between G3 and grade 1&2 (G1&2) in overall survival or progression free survival. Similarly, no survival advantage was found for EEC G3 patients at early stage with different plans of adjuvant treatment. Conclusion: When EEC G3 patients combine with one or more risk factors including LVSI, AI and CSI, lymphadenectomy is recommended. For those with only one factor of G3, it is recommended to evaluate the status of lymph nodes by considering other methods such as sentinel lymph node biopsy technology to avoid overtreatment. Survival analysis showed no difference in EEC G3 cohort compared with G1&2. Also, different plans of adjuvant treatment had no impact on overall survival for EEC G3 patients.

Lymphadenectomy

10.22541/au.159493024.42920545

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Comparison of the effect of levonorgestrel-intrauterine system with or without oral megestrol acetate on fertility-preserving treatment in patients with atypical endometrial hyperplasia: a prospective, open-label, randomized controlled phase II study

Authorea (Authorea) (2022)

Zhiying Xu Bingyi Yang Weiwei Shan Jiongbo Liao Wenyu Shao

Objective To compare the effect of levonorgestrel-intrauterine system (LNG-IUS) with or without oral megestrol acetate (MA) versus MA alone on fertility preserving treatment in patients with atypical endometrial hyperplasia (AEH). Design Single-center phase II study with open-label, randomized and controlled trial conducted between July 2017 and June 2020. Setting Obstetrics & Gynecology Hospital of Fudan University, Shanghai, China Population A total of 180 patients (18-45 years) with primary AEH were randomly assigned (1:1:1) to MA group (N=60), LNG-IUS group (N=60), or MA+LNG-IUS group (N=60). Methods Patients received MA (160 mg orally daily), LNG-IUS, or MA+LNG-IUS (MA 160 mg orally daily plus LNG-IUS), respectively. Main outcomes and measures The primary endpoint was the complete response (CR) rate at 16 weeks of treatment. The secondary endpoints were the CR rate at 32 weeks of treatment, adverse events, recurrent rate, and pregnancy rate. Results LNG-IUS group yielded a higher 16-week CR rate than MA group (P=0.049; Odds ratio [OR], 2.44; 95% confidence interval [95%CI], 1.00-6.00). However, MA+LNG-IUS group did not yield better 16-week or 32-week CR rates than MA group (P=0.245; P=0.915) or LNG-IUS group (P=0.419; P=0.653). Meanwhile, less side-effects were found in LNG-IUS group compared with the other two groups. No significant difference was seen in recurrence rates and pregnancy rates among all three groups. Conclusions LNG-IUS might be considered as the first-line choice of fertility-sparing treatment in AEH patients with proper size of uterine cavity. LNG-IUS combined with MA might not provide better treatment effect than MA or LNG-IUS alone.

Levonorgestrel

Endometrial hyperplasia

Clinical endpoint

10.22541/au.165047406.69185815/v1

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2022-RA-170-ESGO Comparison of the effect of levonorgestrel-intrauterine system with or without oral megestrol acetate on fertility-preserving treatment in patients with atypical endometrial hyperplasia: a prospective, open-label, randomized controlled phaseIIstudy

Endometrial cancer (2022)

Zhiying Xu Bingyi Yang Weiwei Shan Jiongbo Liao Wenyu Shao

Introduction/Background

Objective

To compare the effect of levonorgestrel-intrauterine system (LNG-IUS) with or without oral megestrol acetate (MA) versus MA alone on fertility preserving treatment in patients with atypical endometrial hyperplasia (AEH).

Methodology

Design

Single-center phase II study with open-label, randomized and controlled trial conducted between July 2017 and June 2020.

Setting

Shanghai OBGYN Hospital of Fudan University, China

Population

A total of 132 patients (18–45 years) with primary AEH were randomly assigned (1:1:1) to MA group (N=60), LNG-IUS group (N=60), or MA+LNG-IUS group (N=60).

Methods

Patients received MA (160 mg orally daily), LNG-IUS, or MA+LNG-IUS (MA 160 mg orally daily plus LNG-IUS). Main outcomes and measures The primary endpoint was complete response (CR) rate at 16 weeks of treatment. The secondary endpoints were CR rate at 32 weeks of treatment, adverse events, recurrent rate, and pregnancy rate.

Results

LNG-IUS group yielded higher 16-week CR rate than MA group (P=0.048; Odds ratio [OR], 2.44; 95% confidence interval [95%CI], 1.00–6.00). MA+LNG-IUS group did not yield better 16-week or 32-week CR rates than MA group (P=0.245; P=0.915) or LNG-IUS group (P=0.419; P=0.653). LNG-IUS group achieved less weight gain, nocturnal urine, night sweats, insomnia, or edema face compared with the other two groups. Recurrence rates and pregnancy rates showed no difference among the three groups.

Conclusion

Our data support the usage of LNG-IUS as first line choice for fertility sparing treatment in AEH patients with proper uterine cavity size. LNG-IUS combined with MA did not provide better treatment effect than either LNG-IUS alone or MA alone. This study was supported by the National Key Research and Development Program of China (Grant No 2019YFC1005200 and 2019YFC1005204), Shanghai Medical Centre of Key Programs for Female Reproductive Diseases (Grant No. 2017ZZ010616) and sponsored by Shanghai sailing program (Grant No.19YF1404200).

Levonorgestrel

10.1136/ijgc-2022-esgo.199

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Menopausal Status Combined with Serum CA125 Level Significantly Predicted Concurrent Endometrial Cancer in Women Diagnosed with Atypical Endometrial Hyperplasia before Surgery †

Diagnostics (2021)

Yaochen Lou Jiongbo Liao Weiwei Shan Zhiying Xu Xiaojun Chen

About 10-66% of patients with atypical endometrial hyperplasia diagnosed before surgery (preoperative-AEH) are found to have concurrent endometrial cancer (EC) at definitive hysterectomy, leading to incomplete primary surgery and delayed adjuvant treatment. This study aims to investigate the potential risk factors of concurrent EC in preoperative-AEH patients in a clinical setting with a gynecological pathology review. All patients diagnosed with AEH by endometrial biopsy or curettage that then underwent definitive hysterectomy from January 2016 to December 2019 in a tertiary hospital were retrospectively analyzed. All diagnoses were reviewed by gynecological pathologists. A total of 624 preoperative-AEH patients were included, 30.4% of whom had concurrent EC. In multivariate analysis, postmenopausal status and CA125 ≥ 35 U/mL significantly correlated with concurrent EC (OR = 3.57; 95% CI = 1.80-7.06; OR = 2.15; 95% CI = 1.15-4.03). This risk was remarkably increased in patients with both postmenopausal status and CA125 ≥ 35 U/mL (OR = 16.20; 95% CI = 1.73-151.44). Notably, concurrent EC seemed to occur more frequently in women with postmenopausal time ≥ 5 years (OR = 4.04, 95% CI = 1.80-5.85). In addition, CA125 ≥ 35 U/mL seemed to be an independent risk factor (OR = 5.74; 95% CI = 1.80-18.27) for concurrent intermediate-high-risk EC. Intermediate-high-risk EC was also more commonly seen in preoperative-AEH women with postmenopausal time ≥ 5 years (OR = 5.52, 95% CI = 1.21-25.19, p = 0.027). In conclusion, preoperative-AEH patients with postmenopausal status or elevated level of CA125 might have a high risk of concurrent EC. Adequate pre-surgical evaluation might be suggested for such patients.

Endometrial biopsy

Endometrial hyperplasia

10.3390/diagnostics12010006

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Single-cell RNA sequencing highlights the unique tumor microenvironment of small cell neuroendocrine cervical carcinoma

Journal of Translational Medicine (2025)

Tianyou Wang Li Zhang Song Mei Bo Wang Jiaqi Liu

Small cell neuroendocrine cervical carcinoma is a highly aggressive tumor characterized by early metastasis, a high recurrence rate, and poor prognosis. This study represents the first instance of single-cell sequencing conducted on small cell neuroendocrine carcinoma of the cervix worldwide. Analysis of gene expression regulatory networks revealed that the transcription factor TFF3 drived up-regulation of ELF3. Furthermore, our findings indicated that the neuroendocrine marker genes and gene regulatory networks associated with small cell neuroendocrine cervical carcinoma differed from those observed in lung, small intestine, and liver neuroendocrine carcinoma within the GEO database, suggesting tissue-specific origins for these malignancies. Overall, this study addresses a significant research in understanding small cell neuroendocrine cervical carcinoma in vivo and provides valuable insights for guiding radiotherapy, chemotherapy, and targeted therapy.

Targeted Therapy

Neuroendocrine cell

10.1186/s12967-024-05977-z

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Comparison of the effect of levonorgestrel-intrauterine system with or without oral megestrol acetate on fertility-preserving treatment in patients with atypical endometrial hyperplasia: A prospective, open-label, randomized controlled phase II study

Gynecologic Oncology (2023)

Zhiying Xu Bingyi Yang Weiwei Shan Jiongbo Liao Wenyu Shao

Levonorgestrel

Clinical endpoint

Endometrial hyperplasia

Intention-to-treat analysis

10.1016/j.ygyno.2023.05.001

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Citations (2)

[Fertility-preserving treatment outcomes in endometrial cancer and atypical hyperplasia patients with different molecular profiles].

PubMed (2023)

W Y Shao Yang‐Ting Dong Q Y Lyu Jiongbo Liao Yu Xue

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。.

Endometrial biopsy

Lynch Syndrome

10.3760/cma.j.cn112141-20230719-00011

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Comparison of the effect of oral megestrol acetate with or without levonorgestrel-intrauterine system on fertility-preserving treatment in patients with early-stage endometrial cancer: a prospective, open-label, randomized controlled phase II trial (ClinicalTrials.gov NCT03241914)

Journal of Gynecologic Oncology (2022)

Zhiying Xu Bingyi Yang Jun Guan Weiwei Shan Jiongbo Liao

To evaluate the effect of levonorgestrel-releasing intrauterine system (LNG-IUS) plus oral megestrol acetate (MA) as fertility-preserving treatment in patients with early-stage endometrial cancer (EEC).In this single-center, phase II study with open-label, randomized and controlled design, young patients (18-45 years) diagnosed with primary EEC were screened, who strongly required fertility-preserving treatment. Patients were randomly assigned (1:1) into MA group (160 mg oral daily) or MA (160 mg oral daily) plus LNG-IUS group. Pathologic evaluation on endometrium retrieved by hysteroscopy was performed every 3 months. The primary endpoint was complete response (CR) rate within 16 weeks of treatment. The secondary endpoints were CR rate within 32 weeks of treatment, adverse events, recurrent and pregnancy rate.Between July 2017 and June 2020, 63 patients were enrolled and randomly assigned. Totally 56 patients (26 in MA group; 28 in MA + LNG-IUS group) were included into primary-endpoint analyses. The median follow-up was 31.6 months (range, 3.1-94.0). No significant difference in 16-week CR rate were found between MA and MA + LNG-IUS groups (19.2% vs. 25.0%, p=0.610; odds ratio=1.40; 95% confidence interval=0.38-5.12), while the 32-week CR rates were also similar (57.1% and 61.5%, p=0.743), accordingly. More women in MA + LNG-IUS group experienced vaginal hemorrhage (46.4% vs. 16.1%; p=0.012) compared with MA group. No intergroup difference was found regarding recurrence or pregnancy rate.Compared with MA alone, the addition of LNG-IUS may not improve the early CR rate for EEC, and may produce more adverse events instead.ClinicalTrials.gov Identifier: NCT03241914.

Clinical endpoint

Levonorgestrel

10.3802/jgo.2023.34.e32

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Verteporfin induced SUMOylation of YAP1 in endometrial cancer.

American Journal of Cancer Research (2020)

Bo Wang Wenyu Shao Yue Shi Jiongbo Liao Xiaojun Chen

Yes-associated protein (YAP or YAP1) has been proposed to function as an oncogene in most cancers, with nuclear localization of YAP1 correlating with poor prognosis. Photosensitizer Verteporfin has been proven as an inhibitor of YAP1 through preventing the combination of YAP1 with TEA domain transcription factor (TEAD). We showed previously that the total and phospho-levels of YAP1 were related to the clinical characteristics and outcomes in endometrial cancer (EC) patients, and that YAP1 promoted the proliferation and metastasis of EC cells in vitro cell line studies and in animal models. We also reported that Verteporfin inhibited cell growth and induced cell death through inhibiting YAP1 in EC in our previous study. However, the mechanism of how Verteporfin inhibits the function of YAP1 remains unclear. In this study, we analyzed the global effects of Verteporfin on cell function by using Reverse Phase Protein Arrays (RPPA) and Ingenuity Pathway Analysis (IPA). Furthermore, we demonstrated that Verteporfin induced the SUMOylation of YAP1 for the first time. Interestingly, we found that the SUMOylation of YAP1 was regulated by YAP1 phosphorylation. Together, our study revealed a novel mechanism by which Verteporfin inhibits the function of YAP1 through regulating YAP1 SUMOylation. Our study may provide a rationale for the clinical use of Verteporfin in endometrial cancer by targeting YAP1.

YAP1

Verteporfin

Hippo signaling pathway

Source

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Citations (18)

Clinical calculator predictive of chemotherapy benefit in stage 1A uterine papillary serous cancers

Gynecologic Oncology (2019)

David Mysona Lynn Tran Paul Tran Paola A. Gehrig Linda Van Le

Calculator

10.1016/j.ygyno.2019.10.017

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Citations (15)