Gynecologic oncology最新文献_第6页

Exploring novel therapeutic targets in vulvar squamous cell carcinoma 探索外阴鳞状细胞癌的新治疗靶点

IF 4.1 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology

Pub Date : 2025-11-22 DOI: 10.1016/j.ygyno.2025.11.009

Madeline Rhind , Khadijah Abdulhaleem , Ryan Zhu , Kelly Wei , Jenny Yi , Amy Jamieson , Lars-Christian Horn , Lien Hoang , Yvette Drew

Objective

Vulvar squamous cell carcinoma (VSCC) is a rare malignancy with limited treatment options for advanced disease. This study investigates potential antibody drug conjugate (ADC) targets and explores the immune microenvironment in VSCC.

Methods

Immunohistochemistry (IHC) was performed on tissue microarrays (TMAs) with cores from patients with VSCC to evaluate 6 potential ADC targets: Human Epidermal Growth Factor Receptor 2 (HER2), Trophoblast Cell Surface Antigen 2 (TROP2), Tissue Factor (TF), NECTIN4, Folate Receptor Alpha (FOLR1) and Claudin-18.2 (CLDN18.2). Expression of TROP2, TF and NECTIN4 was quantified using H-score. Multiplex IHC assessed immune markers (CD3+, CD8+, CD68+, PD-1/PD-L1) and combined positive scores (CPS) for programmed death-ligand 1 (PD-L1) were calculated. Clinical data was collected, including p16 and p53 status.

Results

CLDN18.2 and FOLR1 were negative in all cases (n = 108) and HER2 expression was seen in only 2 cases. Intermediate to high H-score (100−300) was observed for TF in 73 % (n = 78), TROP2 in 74 % (n = 80), and NECTIN4 in 53 % (n = 57). All cases had a PD-L1 CPS ≥1 and median CPS was 66 (IQR 28–100) Exploratory analysis suggests ADC marker expression was not dependent on human papillomavirus (HPV) status. However, HPV-independent tumors appeared to have a higher infiltration of CD8+ and CD68+ cells and higher median CPS compared to HPV-associated tumors.

Conclusions

These findings are hypothesis generating and provide rationale for future clinical trials of ADCs and immune checkpoint inhibitors in VSCC. Results suggest HPV-independent tumors may be immunogenically active.

目的：宫颈鳞状细胞癌（VSCC）是一种罕见的恶性肿瘤，晚期治疗选择有限。本研究探讨了抗体药物偶联物（ADC）的潜在靶点，并探讨了VSCC的免疫微环境。方法利用VSCC患者的组织芯片（TMAs）进行免疫组化（IHC），评估6个潜在的ADC靶点：人表皮生长因子受体2 （HER2）、滋养细胞表面抗原2 （TROP2）、组织因子（TF）、NECTIN4、叶酸受体α (FOLR1)和CLDN18.2。H-score法定量检测TROP2、TF和NECTIN4的表达。计算多重免疫组化评估免疫标记物（CD3+、CD8+、CD68+、PD-1/PD-L1）和程序性死亡配体1 （PD-L1）的联合阳性评分（CPS）。结果cldn18.2和FOLR1均为阴性（n = 108）， HER2表达仅2例。有73%的TF （n = 78）、74%的TROP2 （n = 80）和53%的NECTIN4 （n = 57）出现中高h评分（100 ~ 300）。所有病例的PD-L1 CPS≥1，中位CPS为66 (IQR 28-100)，探索性分析提示ADC标志物的表达不依赖于人乳头瘤病毒（HPV）状态。然而，与hpv相关的肿瘤相比，与hpv无关的肿瘤似乎具有更高的CD8+和CD68+细胞浸润和更高的中位CPS。结论这些发现是假设，并为未来adc和免疫检查点抑制剂在VSCC中的临床试验提供了理论基础。结果提示hpv非依赖性肿瘤可能具有免疫原性活性。

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引用次数: 0

AXL inhibition improves the therapeutic efficacy of trastuzumab in high-risk endometrial cancer AXL抑制可提高曲妥珠单抗治疗高危子宫内膜癌的疗效。

IF 4.1 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology

Pub Date : 2025-11-20 DOI: 10.1016/j.ygyno.2025.11.001

Jo’an Tankou , Sofia Ruau , Anjali Walia , Michael Toboni , Hollie Noia , Maggie Mullen , Kevin Lu , David Mutch , Matthew A. Powell , Emanuel F. Petricoin , Katherine C. Fuh

Objective

Improved treatment options for HER2-expressing tumors are needed, particularly receptor targeted therapies. The receptor tyrosine kinase AXL, which is overexpressed in aggressive endometrial cancers, has been shown to heterodimerize with HER2 and drive resistance to anti-HER2 therapies in other cancers. We investigated this interaction in high-risk endometrial cancer and evaluated whether the AXL inhibitor batiraxcept could enhance the therapeutic effect of trastuzumab.

Methods

We utilized three high-risk primary endometrial cancer cell lines (ARK1 and ARK2, uterine serous carcinoma; PUC198, grade 3 endometrioid adenocarcinoma). Immunofluorescence and proximity ligation assays were performed on an ARK2 tumor, and proximity ligation assay was performed on PUC198 cells to assess the physical interaction of HER2 and AXL. Cells were treated with vehicle, batiraxcept, trastuzumab, or both, and colony formation, cell viability, and Matrigel invasion assays were used to assess cell proliferation and invasion. Expression levels of 214 proteins implicated in carcinogenesis were measured via reverse phase protein array. Treatments were also administered to mice injected with ARK1 and ARK2, and tumor burden evaluated via dissection.

Results

Our results demonstrate that AXL and HER2 co-localize and interact in high-risk endometrial cancer cells. We also showed that batiraxcept addition to trastuzumab decreased cell viability and worked synergistically to reduce cell proliferation and invasion in vitro and tumor burden in vivo. Reverse phase protein array analysis revealed that the proteins HER2, phosphorylated HSP-27, Ki-67, LRG1, and LDH-A were downregulated by trastuzumab, and further downregulated by the combination therapy.

Conclusions

Our findings support the combination of batiraxcept and trastuzumab as a promising therapeutic strategy for aggressive HER2+ endometrial cancer.

目的：需要改进her2表达肿瘤的治疗选择，特别是受体靶向治疗。在侵袭性子宫内膜癌中过度表达的受体酪氨酸激酶AXL已被证明与HER2异源二聚化，并在其他癌症中驱动抗HER2治疗的耐药性。我们在高危子宫内膜癌中研究了这种相互作用，并评估了AXL抑制剂batiraexept是否可以增强曲妥珠单抗的治疗效果。方法：选用3种高危原发性子宫内膜癌细胞系（子宫浆液性癌ARK1和ARK2； 3级子宫内膜样腺癌PUC198）。在ARK2肿瘤上进行免疫荧光和接近结扎实验，在PUC198细胞上进行接近结扎实验以评估HER2和AXL的物理相互作用。细胞分别用载体、batiraxept、曲妥珠单抗或两者处理，使用集落形成、细胞活力和Matrigel侵袭试验来评估细胞增殖和侵袭。通过逆相蛋白阵列检测214种致癌相关蛋白的表达水平。对注射了ARK1和ARK2的小鼠进行治疗，并通过解剖评估肿瘤负荷。结果：我们的研究结果表明，AXL和HER2在高危子宫内膜癌细胞中共定位并相互作用。我们还发现，除曲妥珠单抗外，巴替拉还能降低细胞活力，并协同作用，减少体外细胞增殖和侵袭以及体内肿瘤负荷。反相蛋白阵列分析显示，HER2、磷酸化的HSP-27、Ki-67、LRG1和LDH-A蛋白在曲妥珠单抗下下调，在联合治疗下进一步下调。结论：我们的研究结果支持batiraexept和曲妥珠单抗联合治疗侵袭性HER2+子宫内膜癌是一种有希望的治疗策略。

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引用次数: 0

Human fallopian tube epithelial organoids with TP53 mutation recapitulate features of serous tubal intraepithelial carcinoma (STIC) TP53突变的人输卵管上皮类器官与浆液性输卵管上皮内癌（STIC）的概括特征

IF 4.1 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology

Pub Date : 2025-11-20 DOI: 10.1016/j.ygyno.2025.10.038

Judith Kraiczy , Bo Yu

Objective

Serous tubal intraepithelial carcinoma (STIC) is the immediate precursor lesion for high-grade serous ovarian carcinoma (HGSOC) and harbors universal TP53 mutations. The lack of an appropriate in vitro model for STIC presents a major challenge in studying its pathogenesis. We aimed to develop a human in vitro model that mimics STIC lesions.

Methods

Using CRISPR-Cas9 gene editing, we generated human fallopian tube epithelial organoids with TP53 loss-of-function mutations (TP53^-/- FTOs). We characterized TP53^-/- FTOs on a cellular and molecular level using immunofluorescence confocal imaging, copy number variation (CNV) analysis, and RNA sequencing.

Results

TP53^-/- FTOs recapitulated key features of STIC lesions. They exhibited increased proliferation and nuclear abnormalities, including nuclear enlargement and atypical mitotic figures. Copy number variation analysis revealed aneuploidy in some TP53^-/- FTOs. Compared to unedited controls, TP53^-/- FTOs demonstrated significant transcriptomic changes, including the downregulation of DNA repair genes and upregulation of epithelial-mesenchymal transition (EMT) pathways. Similar to STIC lesions, TP53^-/- FTOs showed a marked reduction in ciliated cells and ciliogenesis-associated gene expression.

Conclusions

These findings suggest that p53 loss in FTOs promotes a proliferative and genomically unstable state that is conducive to carcinogenesis. The TP53^-/- FTO model we have generated provides a valuable tool for studying early events in ovarian carcinogenesis and for developing new strategies for the early detection and prevention of ovarian cancer.

目的：输卵管上皮内癌（STIC）是高级别浆液性卵巢癌（HGSOC）的直接前体病变，具有普遍的TP53突变。缺乏合适的STIC体外模型是研究其发病机制的主要挑战。我们的目标是建立一个模拟STIC病变的人体体外模型。方法利用CRISPR-Cas9基因编辑技术，制备了TP53功能缺失突变（TP53-/- FTOs）人输卵管上皮类器官。我们利用免疫荧光共聚焦成像、拷贝数变异（CNV）分析和RNA测序在细胞和分子水平上表征了TP53-/- FTOs。结果stp53 -/- FTOs反映了STIC病变的主要特征。它们表现出增殖增加和核异常，包括核增大和非典型有丝分裂象。拷贝数变异分析显示部分TP53-/- FTOs存在非整倍性。与未编辑的对照组相比，TP53-/- FTOs表现出显著的转录组变化，包括DNA修复基因的下调和上皮-间质转化（EMT）途径的上调。与STIC病变相似，TP53-/- FTOs显示纤毛细胞和纤毛发生相关基因表达显著减少。结论FTOs中p53的缺失促进了增殖和基因组不稳定状态，有利于癌变。我们建立的TP53-/- FTO模型为研究卵巢癌发生的早期事件和开发卵巢癌的早期发现和预防的新策略提供了有价值的工具。

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引用次数: 0

Obstetric and perinatal outcomes following a diagnosis of gynecologic cancer during pregnancy 妊娠期诊断妇科癌症后的产科和围产期结局。

IF 4.1 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology

Pub Date : 2025-11-19 DOI: 10.1016/j.ygyno.2025.11.007

Yiran Shi , Leo Gkekos , Kenny A. Rodriguez-Wallberg , Irma Fredriksson , Magnus Frödin , Frida E. Lundberg , Anna L.V. Johansson

Introduction

Around 5 in 100,000 pregnancies are affected by maternal gynecologic cancer, and the incidence is increasing. We investigated if gynecologic cancer diagnosed during pregnancy influences the risk of adverse obstetric and perinatal outcomes.

Material and methods

This population-based matched study included singleton births registered between 1973 and 2017 in the Swedish Medical Birth Register to women without previous cancer (N = 4,481,808). Births where maternal cancer of the genital organs were diagnosed during pregnancy (n = 269) were identified, and 26,900 cancer-free comparators were matched on maternal age and year of delivery, and birth order. Adjusted conditional logistic and multinomial logistic regression were used to estimate odds ratios (OR) and relative risk ratios (RRR).

Results

Among the 269 women diagnosed with cancer, 196 were cervical cancer, 64 ovarian cancer and 9 other gynecologic cancer types. Maternal gynecologic cancer was associated with higher risks of preterm birth (34–36 weeks: RRR 8.7, 95 % CI 6.2–12.1; 32–33 weeks: 41.0, 26.5–63.5; <32 weeks: 34.8, 22.9–53.0) and cesarean delivery (OR 11.6, 95 % CI 9.0–15.0). Planned preterm delivery was significantly (p < 0.001) more common in cases (36.6 %) than comparator births (0.4 %), as was spontaneous preterm delivery (9.7 % vs 4.4 %, p < 0.001). A higher risk of stillbirth was observed (OR 4.4, 95 % CI 1.6–12.1) based on 4 events among cases, who were all delivered preterm.

Conclusions

Gynecologic cancer during pregnancy was associated with higher risks of preterm birth and adverse preterm-related outcomes. The risks of maternal pregnancy complications and low birth weight for gestational age were similar to those of cancer-free births.

导读：每10万名孕妇中约有5人患有妇科癌症，且发病率呈上升趋势。我们调查了怀孕期间诊断的妇科癌症是否会影响不良产科和围产期结局的风险。材料和方法：这项以人群为基础的匹配研究包括1973年至2017年在瑞典医学出生登记处登记的未患癌症的单胎出生妇女（N = 4,481,808）。确定了在怀孕期间被诊断出患有生殖器官癌症的产妇（n = 269），并根据产妇的年龄、分娩年份和出生顺序匹配26900名无癌症的比较者。采用调整条件逻辑回归和多项逻辑回归估计优势比（OR）和相对风险比（RRR）。结果：269名确诊为癌症的女性中，196名为宫颈癌，64名为卵巢癌，9名为其他妇科癌症。产妇妇科癌症与早产的高风险相关(34-36周：RRR 8.7, 95% CI 6.2-12.1； 32-33周：41.0,26.5-63.5；结论：妊娠期妇科癌症与早产的高风险和不良的早产相关结局相关。孕妇妊娠并发症和低胎龄出生体重的风险与无癌症分娩的风险相似。

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引用次数: 0

Circulating tumor DNA monitoring in ovarian cancer patients receiving PARPi maintenance therapy: Can we further personalize treatment? 接受PARPi维持治疗的卵巢癌患者循环肿瘤DNA监测：我们能进一步个性化治疗吗？

IF 4.1 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology

Pub Date : 2025-11-17 DOI: 10.1016/j.ygyno.2025.11.005

Michael D. Toboni , Elizabeth T. Evans , Carly Bess Scalise , Melissa Hardesty , Tara Berman , Kaitlyn Dinkins , Fibiana Oladipo , Nicole Hook , Jenifer Ferguson , Punashi Dutta , Jennah Moore , Bailee Oliver , Minetta C. Liu , Adam C. ElNaggar , Charles A. Leath III , Rebecca C. Arend

Objectives

Recommendations for the length of maintenance therapy with poly (ADP-ribose) polymerase inhibitors (PARPi) in patients with ovarian cancer (OC) are derived from clinical trials with various durations of therapy. Here, we evaluated whether circulating tumor DNA (ctDNA) predicted recurrence/progression in OC patients receiving PARPi maintenance.

Methods

This was a multi-center retrospective cohort study of real-world data from commercial ctDNA testing (Signatera™, Natera, Inc.) in patients with OC on PARPi maintenance following response to penultimate platinum-based therapy. Clinical data were collected on stage, setting, pathologic subtype, and biomarker status.

Results

Fifty-three patients with OC were analyzed, with samples collected: i) prior to starting PARPi (pre-PARPi; N = 12), ii) during the first 12 months on PARPi (early; N = 34), and iii) beyond 12 months of PARPi therapy (late; N = 26). ctDNA was detected prior to PARPi initiation in 58 % (7/12) of patients, and none experienced sustained ctDNA clearance on PARPi therapy. Notably, none of the ctDNA-negative patients recurred at the last known clinical follow-up. Persistent/conversion to ctDNA positivity within the first 3 months of therapy was associated with significantly shorter progression-free survival (PFS) (p = 0.01). Patients who were serially ctDNA-negative/cleared ctDNA within 6 months on therapy had significantly improved PFS compared to those who were persistently positive/converted to positive (p = 0.003). Correlation with CA-125 and BRCA/HR status was not significant.

Conclusions

ctDNA status on-PARPi was a stronger predictor of disease progression compared to CA-125 or BRCA/HR status. While additional analyses are warranted, our data suggest that ctDNA is a promising biomarker for therapeutic decision-making.

目的：卵巢癌（OC）患者使用聚（adp -核糖）聚合酶抑制剂（PARPi）维持治疗时间的建议来自不同治疗时间的临床试验。在这里，我们评估循环肿瘤DNA （ctDNA）是否预测接受PARPi维持的OC患者的复发/进展。方法：这是一项多中心回顾性队列研究，来自商业ctDNA检测（Signatera™，Natera, Inc.）的真实世界数据，用于接受第二轮铂类治疗后PARPi维持的OC患者。收集临床资料，包括分期、环境、病理亚型和生物标志物状态。结果：分析了53例OC患者，收集的样本：i)开始PARPi之前（PARPi前，N = 12）， ii) PARPi治疗的前12个月（早期，N = 34）， iii) PARPi治疗12个月后（晚期，N = 26）。58%（7/12）的患者在PARPi开始前检测到ctDNA，没有人在PARPi治疗后持续清除ctDNA。值得注意的是，在最后一次已知的临床随访中，没有ctdna阴性的患者复发。在治疗的前3个月内持续/转化为ctDNA阳性与显著缩短的无进展生存期（PFS）相关（p = 0.01）。在治疗6个月内连续ctDNA阴性/清除ctDNA的患者与持续阳性/转化为阳性的患者相比，PFS显著改善（p = 0.003）。CA-125与BRCA/HR状态相关性不显著。结论：与CA-125或BRCA/HR状态相比，parpi上的ctDNA状态更能预测疾病进展。虽然需要进一步的分析，但我们的数据表明，ctDNA是一种有前景的治疗决策生物标志物。

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引用次数: 0

Effect of uterine manipulator on stage IB1 to IIA1 cervical cancer: A retrospective cohort study 子宫操纵器对IB1 ~ IIA1期宫颈癌的影响：一项回顾性队列研究。

IF 4.1 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology

Pub Date : 2025-11-14 DOI: 10.1016/j.ygyno.2025.10.037

Wanying Bao , Xinlin He , Yue Huang , Aoshuang Xing , Zhengyu Li

Objective

This study aimed to evaluate the survival and surgical safety of using a uterine manipulator during laparoscopic radical hysterectomy (LRH) for early-stage cervical cancer.

Methods

We retrospectively analyzed 673 patients with FIGO stage IB1 – IIA1 cervical cancer who underwent LRH between 2019 and 2022. Patients were divided into the uterine manipulator group (n = 395) and the uterine manipulator-free group (n = 278). Propensity score matching (PSM) was performed to minimize confounding effects. Statistical analysis was conducted on perioperative characteristics, pathological results, and follow-up data.

Results

In the unmatched cohort, no significant differences were observed between the uterine manipulator and uterine manipulator-free groups in 3-year disease-free survival (DFS) rates (94.43 % [95 % CI, 92.20 % – 96.72 %] vs. 93.88 % [95 % CI, 91.11% – 96.74 %]; P = 0.88) or overall survival (OS) rates (98.47 % [95 % CI, 97.27 % – 99.69 %] vs. 96.76 % [95 % CI, 94.70 % – 98.86 %]; P = 0.72). In the PSM-matched cohort, 3-year DFS (P = 0.53) and OS (P = 0.94) also showed no significant difference. Five-year survival rates were consistent with these findings. After PSM, multivariate Cox regression analysis identified FIGO stage (2018) IIA1 (HR, 5.82; 95 % CI, 1.11–30.69; P = 0.038) and ovarian invasion (HR, 26.82; 95 % CI, 1.22–589.87; P = 0.037) as the independent risk factors for 3-year DFS. No significant differences were found in major intraoperative complications.

Conclusion

In patients with FIGO stage IB1 – IIA1 cervical cancer, uterine manipulator use during laparoscopic radical hysterectomy does not impact survival and safety.

目的：本研究旨在评价腹腔镜下早期宫颈癌根治性子宫切除术（LRH）中使用子宫机械手的生存率和手术安全性。方法：我们回顾性分析了673例FIGO分期IB1 - IIA1宫颈癌患者在2019年至2022年期间接受了LRH。将患者分为子宫操纵器组（395例）和不使用子宫操纵器组（278例）。采用倾向评分匹配（PSM）来减少混杂效应。对围手术期特征、病理结果及随访资料进行统计分析。结果：在未匹配队列中，子宫操纵器组与无子宫操纵器组3年无病生存率（DFS）（94.43% [95% CI, 92.20% - 96.72%]比93.88% [95% CI, 91.11% - 96.74%], P = 0.88）或总生存率（OS）（98.47% [95% CI, 97.27% - 99.69%]比96.76% [95% CI, 94.70% - 98.86%], P = 0.72）无显著差异。在psm匹配的队列中，3年DFS （P = 0.53）和OS （P = 0.94）也无显著差异。5年生存率与这些发现一致。PSM后，多因素Cox回归分析确定FIGO分期（2018）IIA1 （HR, 5.82; 95% CI, 1.11-30.69; P = 0.038）和卵巢侵犯（HR, 26.82; 95% CI, 1.22-589.87; P = 0.037）为3年DFS的独立危险因素。术中主要并发症无显著性差异。结论：FIGO期IB1 - IIA1宫颈癌患者在腹腔镜根治性子宫切除术中使用子宫机械手不影响生存率和安全性。

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引用次数: 0

The impact of cervical diameter on success of sentinel lymph node mapping in endometrial carcinoma: A retrospective cohort study 宫颈直径对子宫内膜癌前哨淋巴结定位成功的影响：一项回顾性队列研究。

IF 4.1 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology

Pub Date : 2025-11-14 DOI: 10.1016/j.ygyno.2025.11.002

Ashton B. Ariola , Birx Nolan , Lynette Johnson , Mary J. Cunningham

Objective

This study aimed to evaluate the effects of anatomical variation in cervical diameter and length on bilateral sentinel lymph node (SLN) mapping outcomes in endometrial carcinoma.

Methods

A retrospective cohort study was conducted including 341 patients with endometrial carcinoma who underwent SLN mapping from 2016 to 2019, via superficial and deep intracervical injection of indocyanine green at the 3′ and 9′ o'clock positions. Preoperative characteristics abstracted from chart review include BMI, age, and prior abdominal surgery. Peri- and postoperative collected characteristics included number of sentinel lymph nodes detected, cervix diameter and length, uterine weight and diameter, FIGO grade, estimated blood loss, operation length, and the American Society of Anesthesiologists (ASA) physical status classification.

Results

Increased cervical diameter was independently associated with mapping failure (OR 2.13; 95 % CI, 1.27–3.58; p = 0.004) while variations in cervical length were not. Higher BMI and older age were also significantly associated with unsuccessful mapping.

Conclusions

Cervical diameter is an important variable predicting failure to map bilateral sentinel lymph nodes during surgical staging of endometrial carcinoma. Modification of injection techniques based on cervical diameter should be considered for investigation to improve SLN mapping outcomes.

目的：探讨宫颈直径和长度的解剖变化对子宫内膜癌双侧前哨淋巴结（SLN）定位结果的影响。方法：对2016 - 2019年341例子宫内膜癌患者进行回顾性队列研究，在3′和9′位置进行宫颈浅表和深部注射吲哚菁绿。从图表回顾中提取的术前特征包括BMI、年龄和既往腹部手术。围手术期和术后收集的特征包括检测到的前哨淋巴结数量、宫颈直径和长度、子宫重量和直径、FIGO分级、估计失血量、手术时长以及美国麻醉医师协会（ASA）的身体状态分类。结果：宫颈直径增加与定位失败独立相关（OR 2.13; 95% CI, 1.27-3.58; p = 0.004），而宫颈长度变化与定位失败无关。较高的BMI和年龄也与不成功的定位显著相关。结论：宫颈直径是子宫内膜癌手术分期中预测双侧前哨淋巴结定位失败的重要变量。应考虑根据颈椎直径修改注射技术，以改善SLN制图结果。

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引用次数: 0

Comparison of breast and gastric HER2 immunohistochemistry (IHC) scoring criteria in the assessment of endometrial carcinoma 乳腺和胃HER2免疫组织化学（IHC）评分标准在子宫内膜癌评估中的比较。

IF 4.1 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology

Pub Date : 2025-11-13 DOI: 10.1016/j.ygyno.2025.10.034

Rachel L. Furuya , Whitney Grither , Mark G. Evans , Sharon Wu , Jaclyn F. Hechtman , Harris B. Krause , Andrew Elliott , Cara Mathews , Matthew T. Oliver , Katherine Miller , Shuanzeng Wei , Rouba Ali-Fehmi , David A. Bryant , Matthew J. Oberley , Matthew A. Powell , Premal H. Thaker

Background

Immunohistochemistry (IHC) testing is the primary method to determine HER2 status at many institutions, often with reflex to in situ hybridization (ISH). DNA- and RNA- based platforms are emerging for HER-2 assessment. While approved IHC algorithms exist for HER2 scoring in breast and gastric carcinomas, neither has been validated in endometrial cancer. This study seeks to compare them and evaluate patterns of DNA and RNA expression.

Methods

263 endometrioid endometrial adenocarcinoma (EEA), 275 serous endometrial carcinoma (SEC), and 214 uterine carcinosarcoma (UCS) specimens were randomly selected. Previously stained HER2 IHC slides underwent blinded review by two board-certified pathologists and were scored utilizing gastric and breast criteria. Tumors were analyzed for ERBB2 copy number amplification by DNA sequencing and ERBB2 RNA expression by RNA sequencing. Statistical significance was determined using unpaired t-test.

Results

Concordance between scoring algorithms was high for HER2-positive (95 %) and HER2-negative (88 %) cases. Of discordant tumors, the majority (89.7 % of EEA, 68.8 % of SEC, and 81.8 % of UCS) were negative by breast but equivocal by gastric criteria. RNA expression levels were significantly different between discordant cases and negative cases and between negative and equivocal cases. HER2-positivity was associated with worse survival in EEC, improved in SEC, and no difference in UCS.

Conclusions

Breast and gastric scoring criteria show high concordance in endometrial carcinoma, with discordance primarily in equivocal tumors. RNA expression may help stratify equivocal from negative cases. Further study is needed to determine whether HER2 alterations at the DNA, RNA, or protein level predict response to newer generation HER2-targeted therapies.

背景：免疫组织化学（IHC）检测是许多机构确定HER2状态的主要方法，通常采用反射原位杂交（ISH）。基于DNA和RNA的HER-2评估平台正在出现。虽然已批准的IHC算法用于乳腺癌和胃癌的HER2评分，但均未在子宫内膜癌中得到验证。本研究旨在比较它们并评估DNA和RNA的表达模式。方法：随机选取子宫内膜样子宫内膜腺癌（EEA） 263例，浆液性子宫内膜癌（SEC） 275例，子宫癌肉瘤（UCS） 214例。先前染色的HER2 IHC切片由两名委员会认证的病理学家进行盲法审查，并使用胃和乳房标准进行评分。用DNA测序分析肿瘤ERBB2拷贝数扩增，用RNA测序分析肿瘤ERBB2 RNA表达。采用非配对t检验确定统计学显著性。结果：在her2阳性（95%）和her2阴性（88%）病例中，评分算法之间的一致性很高。在不一致的肿瘤中，大多数（89.7%的EEA， 68.8%的SEC和81.8%的UCS）乳房检查为阴性，但胃检查标准不明确。RNA表达水平在不一致病例与阴性病例、阴性病例与模棱两可病例之间存在显著差异。her2阳性与EEC中较差的生存相关，在SEC中改善，在UCS中无差异。结论：乳腺和胃的评分标准在子宫内膜癌中显示出高度的一致性，主要在模棱两可的肿瘤中不一致。RNA表达可能有助于从阴性病例中区分模棱两可的病例。需要进一步的研究来确定HER2在DNA、RNA或蛋白质水平上的改变是否能预测对新一代HER2靶向治疗的反应。

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引用次数: 0

Comparison of oncologic outcomes between completion hysterectomy and no completion hysterectomy in patients who achieved complete response and completed childbearing after fertility-sparing treatment for early-stage endometrial cancer: Gynecologic Oncology Research Investigators coLLaborAtion study (GORILLA-3001) 早期子宫内膜癌保留生育治疗后达到完全缓解并完成生育的患者完成子宫切除术与未完成子宫切除术的肿瘤预后比较：妇科肿瘤学研究研究者合作研究（GORILLA-3001）

IF 4.1 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology

Pub Date : 2025-11-13 DOI: 10.1016/j.ygyno.2025.10.036

A Jin Lee , Eun Bi Jang , Dong Hoon Suh , Suk-Joon Chang , Hee Seung Kim , Ji Geun Yoo , Sung Jong Lee , Yoo-Young Lee , Eun Ji Nam , Seung-Hyuk Shim

Objective

This study evaluated oncological outcomes of completion hysterectomy versus no completion hysterectomy in patients who completed childbearing after achieving complete response (CR) with fertility-sparing treatment (FST) for early-stage endometrial cancer (EC).

Methods

Multicenter data were retrospectively reviewed for patients with presumed stage IA, grade 1 endometrioid EC who gave birth after achieving CR with FST using progestin from 2005 to 2022. Oncologic outcomes were compared between patients who underwent completion hysterectomy and those who did not.

Results

Of 338 patients who achieved CR with FST, including those with second or third CR after relapses, 79 (52.7 %, 79/150) became pregnant (seven miscarriages, 72 live births). Completion hysterectomy was performed in 14 of 72 patients after delivery. During a median follow-up time of 61.0 months (range, 13–144) for the entire cohort, recurrence rates were 0 % (0/14) in the hysterectomy group and 22.4 % (13/58) in the non-hysterectomy group (P = 0.055). Progestin re-treatment was administered to 8 of 13 patients who relapsed, and CR was achieved in all. One patient, after a second live birth following re-treatment, was diagnosed with stage IVB extra-uterine disease during follow-up without completion hysterectomy. Five patients underwent hysterectomy immediately after recurrence, and none had extra-uterine disease. In multivariate analysis, recurrence before childbirth (HR 3.8, 95 % CI 1.0–13.3; p < 0.05) was significantly associated with recurrence after pregnancy.

Conclusion

Completion hysterectomy is associated with improved oncologic outcomes in patients who deliver after FST. Therefore, hysterectomy should be considered for patients who have completed childbearing after FST.

目的：本研究评估早期子宫内膜癌（EC）患者在完全缓解（CR）和保留生育能力治疗（FST）后完成生育的完全子宫切除术与未完成子宫切除术的肿瘤学结果。方法回顾性分析2005年至2022年孕激素FST达到CR后分娩的推定IA期1级子宫内膜样EC患者的多中心数据。肿瘤预后比较了完成子宫切除术的患者和未完成子宫切除术的患者。结果在338例FST患者（包括复发后第二次或第三次CR）中，79例（52.7%,79/150）成功妊娠（7例流产，72例活产）。72例患者中有14例在分娩后进行了完全子宫切除术。在整个队列的中位随访时间为61.0个月（范围13-144），子宫切除术组的复发率为0%(0/14)，非子宫切除术组的复发率为22.4% (13/58)（P = 0.055）。13例复发患者中8例接受黄体酮再治疗，全部达到CR。1例患者，在再次治疗后的第二次活产后，在未完成子宫切除术的随访期间被诊断为IVB期子宫外疾病。5例患者复发后立即行子宫切除术，无一例有子宫外疾病。在多因素分析中，产前复发率（HR 3.8, 95% CI 1.0-13.3; p < 0.05）与妊娠后复发率显著相关。结论完全性子宫切除术可改善FST术后分娩患者的肿瘤预后。因此，FST后完成生育的患者应考虑子宫切除术。

{"title":"Comparison of oncologic outcomes between completion hysterectomy and no completion hysterectomy in patients who achieved complete response and completed childbearing after fertility-sparing treatment for early-stage endometrial cancer: Gynecologic Oncology Research Investigators coLLaborAtion study (GORILLA-3001)","authors":"A Jin Lee , Eun Bi Jang , Dong Hoon Suh , Suk-Joon Chang , Hee Seung Kim , Ji Geun Yoo , Sung Jong Lee , Yoo-Young Lee , Eun Ji Nam , Seung-Hyuk Shim","doi":"10.1016/j.ygyno.2025.10.036","DOIUrl":"10.1016/j.ygyno.2025.10.036","url":null,"abstract":"<div><h3>Objective</h3><div>This study evaluated oncological outcomes of completion hysterectomy versus no completion hysterectomy in patients who completed childbearing after achieving complete response (CR) with fertility-sparing treatment (FST) for early-stage endometrial cancer (EC).</div></div><div><h3>Methods</h3><div>Multicenter data were retrospectively reviewed for patients with presumed stage IA, grade 1 endometrioid EC who gave birth after achieving CR with FST using progestin from 2005 to 2022. Oncologic outcomes were compared between patients who underwent completion hysterectomy and those who did not.</div></div><div><h3>Results</h3><div>Of 338 patients who achieved CR with FST, including those with second or third CR after relapses, 79 (52.7 %, 79/150) became pregnant (seven miscarriages, 72 live births). Completion hysterectomy was performed in 14 of 72 patients after delivery. During a median follow-up time of 61.0 months (range, 13–144) for the entire cohort, recurrence rates were 0 % (0/14) in the hysterectomy group and 22.4 % (13/58) in the non-hysterectomy group (<em>P</em> = 0.055). Progestin re-treatment was administered to 8 of 13 patients who relapsed, and CR was achieved in all. One patient, after a second live birth following re-treatment, was diagnosed with stage IVB extra-uterine disease during follow-up without completion hysterectomy. Five patients underwent hysterectomy immediately after recurrence, and none had extra-uterine disease. In multivariate analysis, recurrence before childbirth (HR 3.8, 95 % CI 1.0–13.3; <em>p</em> < 0.05) was significantly associated with recurrence after pregnancy.</div></div><div><h3>Conclusion</h3><div>Completion hysterectomy is associated with improved oncologic outcomes in patients who deliver after FST. Therefore, hysterectomy should be considered for patients who have completed childbearing after FST.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"203 ","pages":"Pages 191-197"},"PeriodicalIF":4.1,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pathogenic germline variants among patients with ovarian cancer by self-reported ancestry: A commercial laboratory collaborative research registry study 卵巢癌患者中自我报告血统的致病种系变异：一项商业实验室合作研究登记研究

IF 4.1 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology

Pub Date : 2025-11-12 DOI: 10.1016/j.ygyno.2025.11.003

Chinmayi Aryasomayajula , Caitlin R. Johnson , Alex A. Francoeur , Tiffany Y. Sia , Kathleen M. Darcy , Chunqiao Tian , Daniel S. Kapp , John K. Chan , Ying L. Liu

Objective

Ovarian cancer (OC) is highly lethal, and ∼15–20 % of cases occur in patients with germline pathogenic variants (gPVs) in BRCA1/2 and other genes related to homologous recombination (HR) and mismatch repair. We sought to characterize the germline landscape of patients with OC by self-identified ancestry.

Methods

Patients with epithelial OC who received germline testing were identified from the publicly available Myriad Collaborative Research Registry. Rates of gPVs were calculated, overall and by self-reported ancestry, with a focus on HR-related and Lynch syndrome (LS)-associated genes.

Results

Among 84,396 patients with OC, 55,984 (66.3 %) identified as White, 6099 (7.2 %) as Hispanic, 4440 as Black (5.3 %), 3628 (4.3 %) as Ashkenazi Jewish (AJ), 2900 (3.4 %) as Asian, and 19,706 (23.3 %) as Other. Overall, 13,554 (16.1 %) patients had a gPV, with highest rates among AJ (24.4 %), followed by Hispanic (18.8 %), Asian (17.4 %), and White (15.6 %) patients, p < 0.0001. Most gPVs were in HR genes, specifically BRCA1/2, and occurred in 11,661 (13.8 %) patients with significant differences by ancestry, p < 0.001. The highest gPV rates in HR- related genes were in those of AJ ancestry (23.7 %) with similar rates in Hispanic (16.8 %), Asian (15.6 %), Black (14.9 %), and White (13.1 %) populations. Lynch syndrome gPVs were found in 778 (0.92 %) patients with highest rates in Asians (1.3 %).

Conclusions

Among >84,000 patients with OC, 16.1 % had a gPV, supporting recommendations for universal germline testing. Although those of AJ ancestry had the highest prevalence of gPV, Hispanic and Asian patients also had high gPV rates, supporting inclusive testing strategies given universal recommendations.

目的卵巢癌（OC）具有高致死率，约15 - 20%的病例发生在BRCA1/2和其他同源重组（HR）和错配修复相关基因的种系致病变异（gPVs）患者中。我们试图通过自我鉴定的祖先来描述OC患者的种系景观。方法接受生殖系检测的上皮性OC患者来自Myriad协作研究注册中心。通过总体和自我报告的祖先计算gpv的发生率，重点关注hr相关和Lynch综合征（LS）相关基因。结果84,396例OC患者中，白人55,984例（66.3%），西班牙裔6099例（7.2%），黑人4440例（5.3%），德系犹太人（AJ） 3628例（4.3%），亚洲人2900例（3.4%），其他19,706例（23.3%）。总体而言，13554例（16.1%）患者有gPV，其中AJ患者发生率最高（24.4%），其次是西班牙裔（18.8%）、亚洲（17.4%）和白人（15.6%）患者，p < 0.0001。大多数gpv位于HR基因，特别是BRCA1/2基因，发生在11,661例（13.8%）患者中，与祖先有显著差异，p < 0.001。HR相关基因的gPV率最高的是AJ血统（23.7%），西班牙裔（16.8%）、亚洲人（15.6%）、黑人（14.9%）和白人（13.1%）人群的gPV率相似。Lynch综合征gpv在778例（0.92%）患者中被发现，其中亚洲人的发生率最高（1.3%）。结论：在84,000例OC患者中，16.1%的患者有gPV，支持普遍种系检测的建议。尽管AJ血统的患者gPV患病率最高，但西班牙裔和亚洲患者的gPV患病率也很高，这支持了普遍推荐的包容性检测策略。

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引用次数: 0