MRI与CT检查对卵巢癌病理分期及复发转移的诊断价值对比研究

摘要 目的：对比磁共振成像（MRI）与计算机断层扫描（CT）检查对卵巢癌病理分期及复发转移的诊断价值。方法：纳入2017年1月～2019年1月于我院接受诊治的卵巢癌患者100例进行研究。所有患者术前均进行MRI与CT检查,并以术后病理组织活检结果为金标准,对比MRI与CT诊断卵巢癌与卵巢癌病理分期的准确率。所有患者均于首次检查6个月后进行复诊,对比MRI与CT诊断卵巢癌复发转移的准确率。结果：MRI诊断卵巢癌的确诊率为94.00%（94/100）,高于CT诊断的81.00%（81/100）;漏诊率为2.00%（2/100）,低于CT诊断的10.00%（10/100）（均P＜0.05）。MRI诊断卵巢癌Ⅰ期、Ⅱ期、Ⅲ期的准确率分别为93.33%（14/15）、95.00%（19/20）、93.33%（28/30）,高于CT诊断的60.00%（9/15）、65.00%（13/20）、73.33%（22/30）（均P＜0.05）。MRI诊断肠管及周围、盆腔淋巴结、腹膜后淋巴结、肝脏等远处侵袭和转移中的准确率分别为100.00%（26/26）、88.89%（24/27）、75.00%（18/24）、95.00%（19/20）,高于CT诊断的76.92%（20/26）、48.15%（13/27）、41.67%（10/24）、45.00%（9/20）（均P＜0.05）。结论：相较于CT检查,MRI检查诊断卵巢癌的准确率更高,漏诊率更低,且在卵巢癌病理分期以及复发转移的诊断准确率更高,具有较好的临床应用价值。     

彩色多普勒超声评估卵巢癌周围血管受侵程度及可切除性的应用价值

摘要 目的：探讨彩色多普勒超声评估卵巢癌周围血管受侵程度及可切除性的应用价值。方法：选择2018年2月至2019年8月在本院诊治的卵巢癌患者548例作为研究对象,所有患者都给予彩色多普勒超声,评估患者的周围血管受侵程度及可切除性,记录患者的超声血流频谱。结果：超声诊断为卵巢癌周围血管受侵犯78例,占比14.2 %,诊断敏感性与特异性为97.5 %和100.0 %, ROC曲线面积为0.963。超声诊断为卵巢癌可切除450例,占比82.1 %,诊断敏感性与特异性为99.1 %和90.4 %,ROC曲线面积为0.897。手术切除患者的年龄、体重指数、病理类型、病程等与未手术切除患者对比差异无统计学意义(P>0.05)。手术切除患者的搏动指数(pulsation index,PI)和阻力指数(resistance index,RI)高于非手术切除患者,血管舒张末期流速(end-diastolic velocity,EDV)、峰值流速(peak systolic velocity,PSV)低于非手术切除患者,差异均有统计学意义(P<0.05)。结论：彩色多普勒超声评估卵巢癌周围血管受侵程度及可切除性具有很好的敏感性与特异性,有利于指导卵巢癌患者的病情评估与治疗。     

Rac Regulates Vascular Endothelial Growth Factor Stimulated Motility

During angiogenesis endothelial cells migrate towards a chemotactic stimulus. Understanding the mechanism of endothelial cell migration is critical to the therapeutic manipulation of angiogenesis and ultimately cancer prevention. Vascular endothelial growth factor (VEGF) is a potent chemotactic stimulus of endothelial cells during angiogenesis. The endothelial cell signal transduction pathway of VEGF represents a potential target for cancer therapy, but the mechanisms of post-receptor signal transduction including the roles of rho family GTPases in regulating the cytoskeletal effects of VEGF in endothelial cells are not understood.

Here we analyze the mechanisms of cell migration in the mouse brain endothelial cell line (bEND3). Stable transfectants containing a tetracycline repressible expression vector were used to induce expression of Rac mutants. Endothelial cell haptotaxis was stimulated by constitutively active V12Rac on collagen and vitronectin coated supports, and chemotaxis was further stimulated by VEGF. Osteopontin coated supports were the most stimulatory to bEND3 haptotaxis, but VEGF was not effective in further increasing migration on osteopontin coated supports. Haptotaxis on support coated with collagen, vitronectin, and to a lesser degree osteopontin was inhibited by N17 Rac. N17 Rac expression blocked stimulation of endothelial cell chemotaxis by VEGF. As part of the chemotactic stimulation, VEGF caused a loss of actin organization at areas of cell-cell contact and increased stress fiber expression in endothelial cells which were directed towards pores in the transwell membrane. N17 Rac prevented the stimulation of cell-cell contact disruption and the stress fiber stimulation by VEGF.

These data demonstrate two pathways of regulating endothelial cell motility, one in which Rac is activated by matrix/integrin stimulation and is a crucial modulator of endothelial cell haptotaxis. The other pathway, in the presence of osteopontin, is Rac independent. VEGF stimulated chemotaxis, is critically dependent on Rac activation. Osteopontin was a potent matrix activator of motility, and perhaps one explanation for the absence of a VEGF plus osteopontin effect is that osteopontin stimulated motility was inhibitory to the Rac pathway.     

Improved Cellular Response of Osteoblast Cells Using Recombinant Human Osteopontin Protein Produced by <Emphasis Type="Italic">Escherichia coli</Emphasis>

Osteopontin is a major non-collagenous bone matrix protein secreted into the mineralizing extracellular matrix by osteoblasts during bone development. Recombinant human osteopontin (hOPN) that includes the Arg-Gly-Asp (RGD) cell recognition site was expressed in Escherichia coli and the purified osteopontin increased cell adhesion, proliferation and differentiation of osteoblast cells (p<0.05). Revisions requested 26 July 2005; Revisions received 31 August 2005     

Tissue specificity and developmental expression of rat osteopontin

Osteopontin is a 44 kd phosphoprotein abundant in bone matrix. We isolated a partial length cDNA for rat osteopontin and used it to examine its tissue specificity, its expression during bone development and its hormonal regulation. Osteopontin mRNA is most abundant in bone but is also found in considerable amounts in kidney. Osteopontin mRNA is regulated by the osteotropic hormones dexamethasone and 1,25(OH)2D3. Estimates of osteopontin mRNA levels indicate that the osteopontin gene is turned on relatively late in calvarial development.     

Ultrastructural localization of osteopontin immunoreactivity in phagolys osomes and secretory granules of cells in human intestine

A post-embedding ultrastructural immunogold method was used to detect osteopontin in human intestinal biopsies with special emphasis on secretory and phagocytic organelles. Osteopontin immunoreactivity was localized to phagolysosomes of macrophages, fibroblasts, absorptive epithelial cells of the small intestine and Paneth cells. The mucigen secretory granules and Golgi structures of mucous epithelial cells of the small intestinal epithelium contained osteopontin, but secretory granules of numerous other cells, including Paneth cells, did not. Extracellular and phagocytosed Tropheryma whippelii within macrophage phagolysosomes also bound osteopontin. These localizations are supportive of a role for osteopontin in phagocytic and some secretory cell functions in human intestine     

Suppressive activities of mangiferin on human epithelial ovarian cancer

BackgroundEpithelial carcinoma is a subtype of ovarian cancers, with the highest lethality among all ovarian cancer subtypes. Hitherto surgical excision combined with chemotherapy has been the most extensively employed method in clinical treatment. However, the disease relapses very frequently, calling for more effective therapies. Mangiferin, a natural xanthone glucoside, has displayed promising anti-cancer activities by in vitro studies, but its therapeutic value in epithelial ovarian cancer treatment, either by in vivo or in vitro studies, remained to be known.PurposeThis study aimed to determine the suppressive activities of mangiferin on human epithelial ovarian cancer and elucidate the underlying molecular mechanisms.Study design and methodsWe employed the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the crystal violet assay to determine the half maximal inhibitory concentration (IC₅₀) values of mangiferin with paclitaxel as a positive control and the inhibitory effects of mangiferin on the proliferation of two human epithelial ovarian cancer cell lines. Wound healing and Transwell assays were used to determine anti-metastastic activities of mangiferin. ES-2 xenograft nude mouse model was used for the in vivo experiments. Western blotting, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) assays were carried out for evaluating the expression level of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9).ResultsIn the present study, we demonstrated by both in vitro and in vivo assays that mangiferin suppressed the progress of epithelial ovarian cancer in a dose-dependent manner. In the animals treated with mangiferin, the tumor volume and weight were reduced significantly. Analyses of involved molecular events demonstrated that mangiferin down-regulated the expression of metastasis-associated proteins MMP2 and MMP9.ConclusionMangiferin strongly inhibited the progression of human epithelial ovarian cancer by down-regulating MMP2 and MMP9.     

Osteopontin modulates prostate carcinoma invasive capacity through RGD-dependent upregulation of plasminogen activators

Osteopontin, a non-collageneous bone matrix protein, is produced in several human tumors but its role in cancer progression has been only partially elucidated. In this study we investigated the potential role of osteopontin in the malignancy of prostate cancer cells. Chemotaxis and chemoinvasion analyses revealed a dose-dependent increase in PC3 cell movement induced by osteopontin and a strict dependence of cell invasion on alphavbeta3 integrin function. The pattern of protease expression was modified by osteopontin and was characterized by an upregulation of plasminogen activators. Our findings suggest that osteopontin may confer selective malignant potential to prostate cancer cells through the enhancement of their invasive and proteolytic capability.     

Lysophosphatidic acid signaling in ovarian cancer

Abstract

Lysophosphatidic acid (LPA) is a bioactive phospholipid that is involved in signal transduction between cells. Plasma and ascites levels of LPA are increased in ovarian cancer patients even in the early stages and thus LPA is considered as a potential diagnostic marker for this disease. This review presents the current knowledge regarding LPA signaling in epithelial ovarian cancer. LPA stimulates proliferation, migration and invasion of ovarian cancer cells through regulation of vascular endothelial growth factor, matrix metalloproteinases, urokinase plasminogen activator, interleukin-6, interleukin-8, CXC motif chemokine ligand 12/CXC receptor 4, COX2, cyclin D1, Hippo-Yap and growth-regulated oncogene α concentrations. In this article, all of these targets and signal pathways involved in LPA influence are described.     

SLC2A1-AS1在卵巢癌中的表达及临床意义

摘要 目的：探究lncRNA SLC2A1反义RNA 1（SLC2A1 antisense RNA 1,SLC2A1-AS1）在卵巢癌中的表达情况及与卵巢癌患者预后之间的关系,为卵巢癌的诊断和预后提供一种新的生物标志物。方法：通过多个数据库中的卵巢癌样本信息及其实时荧光定量PCR（Real Time Quantitative PCR,RT-qPCR）分别探究SLC2A1-AS1在卵巢癌中的表达情况及其与卵巢癌患者预后之间的关系,通过免疫荧光实验和划痕实验探究SLC2A1-AS1的表达对卵巢癌细胞的增殖和迁移的影响。通过基因本体(Gene ontology,GO)和京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes,KEGG）分析寻找SLC2A1-AS1影响卵巢癌恶性进程的可能机制。结果：基于多个数据库中的生物信息学分析和RT-qPCR验证发现SLC2A1-AS1在卵巢癌中异常低表达,且SLC2A1-AS1低表达与卵巢癌患者的不良预后密切相关。SLC2A1-AS1过表达可明显抑制卵巢癌细胞的增殖和迁移能力。基于GO和KEGG分析,发现SLC2A1-AS1可能通过调控细胞外基质（extracellular matrix,ECM）组分以及ECM受体的相互作用通路抑制卵巢癌的恶性进程。结论：SLC2A1-AS1可能作为一种关键的潜在的生物标志物抑制着卵巢癌的恶性进展。     

WT-1、Smac蛋白在上皮性卵巢癌中的表达和临床意义研究

目的:探讨WT-1和Smac蛋白在上皮性卵巢癌中的表达及其临床意义。方法:应用免疫组织化学染色方法检测40例正常卵巢组织,40例卵巢上皮性良性肿瘤组织,60例全面分期手术治疗的上皮性卵巢癌组织中WT-1、Smac蛋白的表达,并分析WT-1、Smac蛋白的表达与上皮性卵巢癌临床病理特征的相关性及二者之间的相关性。结果:WT-1蛋白在上皮性卵巢癌组织中的表达明显高于正常卵巢组织或卵巢上皮性良性肿瘤组织(P0.05);Smac蛋白在上皮性卵巢癌组织中表达明显低于正常卵巢组织或卵巢上皮性良性肿瘤组织(P0.05)。上皮性卵巢癌组织中WT-1、Smac蛋白的表达与肿瘤临床分期、组织分化程度、淋巴结有无转移均显著相关(P0.05)。且上皮性卵巢癌中WT-1、Smac蛋白的表达呈明显负相关性(r=-0.35,P0.05)。结论:WT-1蛋白高表达或Smac蛋白低表达可能在上皮性卵巢癌的发生、发展中发挥重要作用,检测WT-1、Smac蛋白的表达有助于上皮性卵巢癌恶性程度的判断和预后评估。     

Ultrastructural localization of osteopontin immunoreactivity in phagolys osomes and secretory granules of cells in human intestine

A post-embedding ultrastructural immunogold method was used to detect osteopontin in human intestinal biopsies with special emphasis on secretory and phagocytic organelles. Osteopontin immunoreactivity was localized to phagolysosomes of macrophages, fibroblasts, absorptive epithelial cells of the small intestine and Paneth cells. The mucigen secretory granules and Golgi structures of mucous epithelial cells of the small intestinal epithelium contained osteopontin, but secretory granules of numerous other cells, including Paneth cells, did not. Extracellular and phagocytosed Tropheryma whippelii within macrophage phagolysosomes also bound osteopontin. These localizations are supportive of a role for osteopontin in phagocytic and some secretory cell functions in human intestine This revised version was published online in November 2006 with corrections to the Cover Date.     

卵巢高/低级别浆液性癌的定量蛋白质组学比较研究

目的:探讨卵巢高级别浆液性癌和低级别浆液性癌的差异表达蛋白,为阐明卵巢癌发生机制及寻找诊断和预后标志物的提供线索。方法:收集卵巢癌新鲜组织标本冻存于液氮中,经病理学确诊为高级别浆液性癌和低级别浆液性癌,两种类型各收集15例。应用i TRAQ定量蛋白质组学技术筛选及鉴定高/低级别浆液性癌的差异表达蛋白,并进行生物信息学分析。结果:卵巢高级别和低级别浆液性癌组织的定量蛋白质组学比较研究鉴定出差异表达蛋白314个,其中与低级别浆液性癌组比较,高级别浆液性癌组上调蛋白有97种,下调蛋白有217种。GO分析显示这些差异蛋白在分子功能、生物学功能、细胞成分方面均具有一定分布特点。KEGG分析显示这些差异蛋白涉及复杂的信号通路。结论:高/低级别浆液性癌之间存在差异表达蛋白,这些蛋白涉及复杂的功能和信号通路可能在两型卵巢癌发生机制及肿瘤生物学行为差异中具有重要意义。     

TRPM3表达上调通过调控Beclin1的表达促进卵巢癌细胞自噬

目的:探讨瞬时受体电位离子通道3(TRPM3)和Beclin1在卵巢癌中的表达和对卵巢癌细胞自噬的影响。方法:收集6例正常卵巢组织标本和20例卵巢癌组织标本,应用免疫组织化学染色法检测TRPM3和Beclin1在卵巢癌组织中的表达,采用western blotting法检测TRPM3和Beclin1在正常卵巢上皮细胞Moody和卵巢癌细胞Hey、ES-2中的表达差异。用TRPM3-siRNA瞬时转染细胞Hey和ES-2,通过western blotting法检测TRPM3基因沉默情况及Beclin1、p62和LC3的蛋白表达变化。结果:在正常卵巢组织和卵巢癌组织中,TRPM3的阳性表达率分别为33.3%、80.0%(P0.05),而Beclin1的阳性表达率分别为33.3%、65.0%(P0.05)。与正常卵巢上皮细胞Moody相比,卵巢癌细胞Hey和ES-2中TRPM3、Beclin1蛋白表达水平明显较高(P0.05)。沉默TRPM3基因表达的卵巢癌细胞中Beclin1和LC3蛋白表达与对照组相比明显降低,而p62表达升高(P0.05)。结论:卵巢癌组织和细胞中TRPM3蛋白呈高表达,可能通过调控Beclin1促进卵巢癌细胞的自噬。     

Human omental adipose-derived mesenchymal stem cells enhance autophagy in ovarian carcinoma cells through the STAT3 signalling pathway

BackgroundOur previous study showed that human omental adipose-derived stem cells (ADSCs) promote ovarian cancer growth and metastasis. In this study, the role of autophagy in the ovarian cancer-promoting effects of omental ADSCs was further determined.MethodsThe growth and invasion of ovarian cancer cells were detected by CCK-8 and Transwell assays, respectively. The autophagy of ovarian cancer cells transfected with MRFP-GFP-LC3 adenoviral vectors was evaluated by confocal microscopy and western blot assay. Transfection of STAT3 siRNA was used to inhibit the expression of STAT3.ResultsOur results show that autophagy plays a vital role in ovarian cancer and is promoted by ADSCs. Specifically, we show that proliferation and invasion are correlated with autophagy induction by ADSCs in two ovarian cancer cell lines under hypoxic conditions. Mechanistically, ADSCs activate the STAT3 signalling pathway, thereby promoting autophagy. Knockdown of STAT3 expression using siRNA decreased hypoxia-induced autophagy and decreased the proliferation and metastasis of ovarian cancer cells.ConclusionTaken together, our data indicate that STAT3-mediated autophagy induced by ADSCs promotes ovarian cancer growth and metastasis.     

Effects of adiponectin,plasma D-dimer,inflammation and tumor markers on clinical characteristics and prognosis of patients with ovarian cancer

BackgroundTo investigate the effects of adiponectin (ADPN), plasma D-dimer (D-D), inflammation, and tumour markers on clinical characteristics and prognosis of patients with ovarian cancer.MethodsA total of 80 patients with ovarian cancer treated in our hospital from April 2017 to November 2019 were enrolled as study subjects and evenly divided into an observation group (patients with ovarian cancer) and a control group (patients with the benign ovarian tumour) based on the results of the postoperative pathological biopsy. The levels of ADPN, plasma D-D, inflammatory factors, and serum tumour markers carbohydrate antigen 125 (CA125), human epididymis protein 4 (HE4), and risk of ovarian malignancy algorithm (ROMA) were compared between the two groups. The diagnostic value of serum tumour markers CA125, HE4, and ROMA in ovarian cancer was explored. The correlations of ROMA changes with the changes in the levels of ADPN, plasma D-D, high-sensitivity C-reactive protein (hs-CRP), CA125, and HE4 were analysed. Additionally, the related risk factors affecting the development of ovarian cancer were subjected to univariate and multivariate logistic regression analyses.ResultsIn comparison with the control group, the observation group exhibited a lowered ADPN level (p<0.05), notably raised levels of plasma D-D, inflammatory factors hs-CRP and interleukin-6 (IL-6) and serum tumour markers CA125 and HE4 and an evidently increased ROMA (p<0.05). Besides, the detection of serum ROMA showed the highest specificity and sensitivity and low false-positive rate and false-negative rate. The changes of ROMA were positively correlated with the changes in the levels of plasma D-D, hs-CRP, CA125, and HE4 (p<0.05) and negatively associated with the changes in ADPN level (p<0.05). The results of the univariate analysis showed that abnormal ADPN, D-D, hs-CRP, IL-6, CA125, and HE4 levels were related to risk factors affecting the development of ovarian cancer. It was found through multivariate logistic regression analysis that decreased ADPN level and increased D-D, hsCRP, IL-6, CA125, and HE4 levels were independent risk factors affecting the development of ovarian cancer.ConclusionsIn the case of ovarian cancer, the ADPN level declines, while the levels of plasma D-D, inflammatory factors, and serum tumour markers CA125, HE4, and ROMA rise obviously. Besides, the ROMA level displays a positive relation to the content of CA125, HE4, plasma D-D, and inflammatory factors and a negative association with the ADPN level.     

Intraperitoneal delivery of human natural killer cells for treatment of ovarian cancer in a mouse xenograft model

Background aimsThere is an urgent need for novel therapeutic strategies for relapsed ovarian cancer. Dramatic clinical anti-tumor effects have been observed with interleukin (IL)-2 activated natural killer (NK) cells; however, intravenous delivery of NK cells in patients with ovarian cancer has not been successful in ameliorating disease. We investigated in vivo engraftment of intraperitoneally (IP) delivered NK cells in an ovarian cancer xenograft model to determine if delivery mode can affect tumor cell killing and circumvent lack of NK cell expansion.MethodsAn ovarian cancer xenograft mouse model was established to evaluate efficacy of IP-delivered NK cells. Tumor burden was monitored by bioluminescent imaging of luciferase-expressing ovarian cancer cells. NK cell persistence, tumor burden and NK cell trafficking were evaluated. Transplanted NK cells were evaluated by flow cytometry and cytotoxicity assays.ResultsIP delivery of human NK cells plus cytokines led to high levels of circulating NK and was effective in clearing intraperitoneal ovarian cancer burden in xenografted mice. NK cells remained within the peritoneal cavity 54 days after injection and had markers of maturation. Additionally, surviving NK cells were able to kill ovarian cancer cells at a rate similar to pre-infusion levels, supporting that in vivo functionality of human NK cells can be maintained after IP infusion.ConclusionsIP delivery of NK cells leads to stable engraftment and antitumor response in an ovarian cancer xenograft model. These data support further pre-clinical and clinical evaluation of IP delivery of allogeneic NK cells in ovarian cancer.     

TRPC3对上皮性卵巢癌细胞株迁移和侵袭的影响

目的:探讨瞬时受体电位通道C3(TRPC3)对人卵巢癌细胞迁移、侵袭能力的影响。方法:采用蛋白免疫印迹法和实时荧光定量PCR法分别检测卵巢癌细胞株SKOV3、ES-2和HEY-T30中TRPC3蛋白和m RNA的表达水平。通过Transwell迁移实验(不含Matrigel胶的Transwell小室)和Transwell侵袭实验分别检测卵巢癌细胞株SKOV3、ES-2和HEY-T30的迁移、侵袭能力。结果:在SKOV3、ES-2和HEY-T30三种卵巢癌细胞株中,ES-2中TRPC3的蛋白和m RNA表达均显著高于其他两株(P0.05)。Transwell迁移实验和Transwell侵袭实验显示卵巢癌细胞株ES-2的迁移、侵袭能力均显著高于其他两种细胞株(P0.05)。结论:瞬时受体电位通道C3(TRPC3)在ES-2人卵巢癌细胞中高表达,并可能促进人卵巢癌细胞的迁移、侵袭。     

EGFR和KRAS在上皮性卵巢癌组织中的表达及临床意义

目的:探讨表皮生长因子受体(EGFR)和鼠Kirsten肉瘤病毒致癌基因(KRAS)蛋白在上皮性卵巢癌组织中的表达水平及临床意义。方法:利用免疫组化SP法对上皮性卵巢癌组织(病例组,n=57)、卵巢良性肿瘤组织(良性组,n=50)以及正常卵巢组织(对照组,n=50)中的EGFR、KRAS蛋白水平进行检测,并分析其在上皮性卵巢癌发生发展中的作用。结果:病例组的EGFR、KRAS蛋白阳性率高于良性组和对照组(P0.05),良性组和对照组的EGFR、KRAS蛋白阳性率差异无统计学意义(P0.05)。浆液性腺癌组EGFR、KRAS蛋白的阳性表达率高于非浆液性腺癌组,Ⅲ~Ⅳ期的上皮性卵巢癌组织中EGFR、KRAS蛋白阳性表达率高于Ⅰ~Ⅱ期,中、低分化组中EGFR、KRAS蛋白阳性表达率高于高分化组,差异均具有统计学意义(P0.05)。上皮性卵巢癌组织中EGFR与KRAS的蛋白的阳性表达率呈正相关关系(r=0.469,P0.05)。结论:EGFR及KRAS蛋白在上皮性卵巢癌组织中的表达水平明显升高,可能参与了上皮性卵巢癌的发生发展过程,且两者之间呈正相关关系,联合检测可作为早期诊断上皮性卵巢癌的重要指标。     

Hysterectomy and risk of epithelial ovarian cancer by histologic type,endometriosis, and menopausal hormone therapy

BackgroundThis nationwide, register-based case-control study investigated the association between hysterectomy and risk of epithelial ovarian cancer according to histology and by history of endometriosis and menopausal hormone therapy (MHT) use.MethodsFrom the Danish Cancer Registry, all women registered with epithelial ovarian cancer at age 40–79 years during 1998–2016 were identified (n = 6738). Each case was sex- and age-matched to 15 population controls using risk-set sampling. Information on previous hysterectomy on benign indication and potential confounders was retrieved from nationwide registers. Conditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for the association between hysterectomy and ovarian cancer according to histology, endometriosis, and use of MHT.ResultsHysterectomy was not associated with risk of epithelial ovarian cancer overall (OR=0.99; 95% CI 0.91 –1.09) but was associated with reduced risk of clear cell ovarian cancer (OR=0.46; 95% CI 0.28–0.78). In stratified analyses, decreased ORs associated with hysterectomy were seen in women with endometriosis (OR=0.74; 95% CI 0.50–1.10) and in non-users of MHT (OR=0.87; 95% CI 0.76–1.01). In contrast, among long-term MHT users, hysterectomy was associated with increased odds for ovarian cancer (OR=1.20; 95% CI 1.03–1.39).ConclusionHysterectomy was not associated with epithelial ovarian cancer overall but with reduced risk of clear cell ovarian cancer. Our findings may suggest a reduced risk of ovarian cancer after hysterectomy in women with endometriosis and in MHT non-users. Interestingly our data pointed to an increased ovarian cancer risk associated with hysterectomy among long-term users of MHT.