Chemokine axes CXCL12/CXCR4 and CXCL16/CXCR6 correlate with lymph node metastasis in epithelial ovarian carcinoma

Recent evidence suggests that the chemokine axis of CXC chemokine ligand-12 and its receptor CXC chemokine receptor-4(CXCL12/CXCR4) is highly expressed in gynecological tumors and the axis of CXC chemokine ligand-16 and CXC chemokine receptor-6(CXCL16/CXCR6) is overexpressed in inflammation-associated tumors.This study aimed to determine the relationship between CXCL12/CXCR4,CXCL16/CXCR6 and ovarian carcinoma's clinicopathologic features and prognosis.Accordingly,the expression of these proteins in ovarian tissues was detected by tissue microarray and immunohistochemistry.The expressions of CXCL12/CXCR4 and CXCL16/CXCR6 were significantly higher in epithelial ovarian carcinomas than in normal epithelial ovarian tissues or benign epithelial ovarian tumors.The expression of chemokines CXCL12 and CXCL16 were positively correlated with their receptors CXCR4 and CXCR6 in ovarian carcinoma,respectively(r = 0.300,P < 0.05;r = 0.395,P < 0.05).Moreover,the expression of CXCL12 was related to the occurrence of ascites(χ2 = 4.76,P < 0.05),the expression of CXCR4 was significantly related to lymph node metastasis(χ2 = 4.37,P < 0.05),the expression of CXCR6 was significantly related to lymph node metastasis(χ2 = 7.43,P < 0.05) and histological type(χ2 = 33.48,P < 0.05).In univariate analysis,the expression of CXCR4 and CXCL16 significantly correlated with reduced median survival(χ2 = 4.67,P < 0.05;χ2 = 4.48,P < 0.05).Therefore,we conclude that the chemokine axes CXCL12/CXCR4 and CXCL16/CXCR6 may play important roles in the growth,proliferation,invasion,and metastasis of epithelial ovarian carcinoma.

Surgery in platinum-resistant recurrent epithelial ovarian carcinoma

BACKGROUND Ovarian cancer is one of the three most common malignant tumors of the female reproductive tract and ranks first in terms of mortality among gynecological tumors.Epithelial ovarian carcinoma(EOC)is the most common ovarian malignancy,accounting for 90%of all primary ovarian tumors.The clinical value of cytoreductive surgery in patients with platinum-resistant recurrent EOC remains largely unclear.AIM To evaluate the feasibility of secondary cytoreductive surgery for treating platinum-resistant recurrent EOC.METHODS This was a retrospective study of the clinical data of patients with platinumresistant EOC admitted to the Cancer Hospital of the University of Chinese Academy of Sciences between September 2012 and June 2018.Patient baseline data were obtained from clinical records.Routine follow-up of disease progression was performed as follows.CA125 assessment and physical examination were performed every 3 wk during treatment,including gynecological examination.Imaging assessment was carried out every 12 wk by B-mode ultrasound,computed tomography,or magnetic resonance imaging.The primary outcome was progression-free survival(PFS).Secondary outcomes included overall survival(OS),chemotherapy-free interval(CFI),and complications.Follow-up ended on April 15,2019.RESULTS A total of 38 patients were included.R0 resection was achieved in 25(65.8%) patients and R1/2 in 13 (34.2%). Twenty-five (65.8%) patients required organ resection. Nine(23.7%) patients had operative complications, 36 (94.7%) received chemotherapy, and five (13.2%)had targeted therapy. Median PFS and OS were 10 (95%CI: 8.27-11.73) months and 28 (95%CI:12.75-43.25) months, respectively;median CFI was 9 (95%CI: 8.06-9.94) months. R0 resection andpostoperative chemotherapy significantly prolonged PFS and OS (all P < 0.05), and R0 resectionalso significantly prolonged CFI (P < 0.05). Grade ≥ 3 complications were observed, includingrectovaginal fistula (n = 1), intestinal and urinary fistulas (n = 1), and renal failure-associated death(n = 1). Except for the patient who died after surgery, all other patients with complications weresuccessfully managed. Two patients developed intestinal obstruction and showed improvementafter conservative treatment.CONCLUSIONSecondary cytoreductive surgery is feasible for treating platinum-resistant recurrent EOC. Thesefindings provide important references for the selection of clinical therapeutic regimens.

Usefulness of human epididymis protein 4 in predicting cytoreductive surgical outcomes for advanced ovarian tubal and peritoneal carcinoma

Objective： Human epididymis protein 4（HE4） is a promising biomarker of epithelial ovarian cancer（EOC）. But its role in assessing the primary optimal debulking（OD） of EOC remains unknown. The purpose of this study is to elucidate the ability of preoperative HE4 in predicting the primary cytoreductive outcomes in advanced EOC, tubal or peritoneal carcinoma.Methods： We reviewed the records of 90 patients with advanced ovarian, tubal or peritoneal carcinoma who underwent primary cytoreduction at the Department of Obstetrics and Gynecology of Peking University People＇s Hospital between November 2005 and October 2010. Preoperative serum HE4 and CA125 levels were detected with EIA kit. A receiver operating characteristic（ROC） curve was used to determine the most useful HE4 cut-off value. Logistic regression analysis was performed to identify significant preoperative clinical characteristics to predict optimal primary cytoreduction.Results： OD was achieved in 47.7%（43/48） of patients. The median preoperative HE4 level for patients with OD vs. suboptimal debulking was 423 and 820 pmol/L, respectively（P〈0.001）. The areas under the ROC curve for HE4 and CA125 were 0.716 and 0.599, respectively（P=0.080）. The most useful HE4 cut-off value was 473 pmol/L. Suboptimal cytoreduction was obtained in 66.7%（38/57） of cases with HE4 ≥473 pmol/L compared with only 27.3%（9/33） of cases with HE4 〈473 pmol/L. At this threshold, the sensitivity, specificity, positive predictive value（PPV） and negative predictive value（NPV） for diagnosing suboptimal debulking were 81%, 56%, 67%, and 73%, respectively. Logistic regression analysis showed that the patients with HE4 ≥473 pmol/L were less likely to achieve OD（odds ratio =5.044, P=0.002）.Conclusions： Preoperative serum HE4 may be helpful to predict whether optimal cytoreductive surgery could be obtained or whether extended cytoreduction would be needed by an interdisciplinary team.

Clinical characteristics and survival of patients with normal-sized ovarian carcinoma syndrome: Retrospective analysis of a single institution 10-year experiment

BACKGROUND Normal size ovarian cancer syndrome(NOCS)is a challenge for clinicians regarding timely diagnosis and management due to atypical clinical and imaging features.It is extremely rare with only a few cases reported in the literature.More data are needed to clarify its biological behavior and compare the differences with abnormal size ovarian cancer.AIM To assess the clinical and pathological features of NOCS patients treated in our institution in the last 10 years and to explore risk factors for relapse and survival.METHODS Patients who were pathologically diagnosed with NOCS between 2008 and 2018 were included.Papillary serous ovarian carcinoma(PSOC)patients were initially randomly recruited as the control group.Demographics,tumor characteristics,treatment procedures,and clinical follow-up were retrospectively collected.Risk factors for progression-free survival and overall survival were assessed.RESULTS A total of 110 NOCS patients were included;80(72.7%)had primary adnexal carcinoma,two(1.8%)had mesotheliomas,18(16.4%)had extraovarian peritoneal serous papillary carcinoma,and eight(7.3%)had metastatic tumors.Carbohydrate antigen(CA)125 and ascites quantity were lower in the NOCS cohort than in the PSOC group.The only statistically significant risk factors for worse overall survival(P<0.05)were the levels of CA199 and having fewer than six chemotherapy cycles.The 1-year,3-year,and 5-year survival rates were 75.5%,27.7%,and 13.8%,respectively.CONCLUSION The clinical symptoms of the NOCS group are atypical,and the misdiagnosis rate is high.Ascites cytology and laparoscopic exploration are valuable in the early diagnosis to avoid a misdiagnosis.The level of CA199 is the most important predictor of overall survival,and more than six cycles of chemotherapy contributes to the increased survival rates of NOCS patients.

Three Weeks Carboplatin/Paclitaxel versus Weekly Regimen in Egyptian Women Cohort Treated for Ovarian Carcinoma

Introduction: Epithelial Ovarian Carcinoma (EOC) comprises the vast majority (almost 90%) of ovarian carcinomas. Chemotherapy is the main treatment in ovarian cancers. The standard of care in the chemotherapeutic is the combination of a platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel). Studies were done to determine whether this combination to be given weekly or every 3 weeks. Patient and Method: Inclusion criteria: 1) Female patients between the ages of 17 - 78 years. 2) Baseline hematological, renal and liver laboratory profiles were within accepted ranges. 3) Performance status of the patients was 0-II. 4) Patients were pathologically proven ovarian cancer. 5) A follow-up period for at least 6 months was required. Exclusion criteria: 1) Patients who had double malignancy were excluded. 2) Performance status more than II. 3) Other comorbidity. Results: We reviewed 69 female patients with EOC, with 60% received every three weeks regimen. Mean age was 53.22 years. At a median follow up of 45.9 months, there was no significant different between the two protocols in terms of mean PFS, 62.35 months (95% CI: 50.08 - 74.63 months) for the three-weekly cohort, and 69.25 months (95% CI: 55.24 - 83.26 months) for weekly protocol (p = 0.613). The three weekly regimen patients had a higher incidence of hospital admission (40% vs 18.5% for the weekly protocol patients), but it didn’t reach a statistical significance (p = 0.063). The three weekly protocol had a significantly higher incidence of causing a neutropenic fever (p = 0.003). Conclusion: In our cohort of Egyptian women with EOC, no significant difference in PFS was found when compared the weekly Carboplatin/paclitaxel when compared to the classic three weeks, although the weekly protocol may be causing less febrile neutropenia and fewer hospital admissions.

A retrospective clinical study of neoadjuvant chemotherapy for advanced epithelial ovarian cancer

Objective The aim of this study was to investigate the clinical efficacy of neoadjuvant chemotherapy(NACT) and the prognostic factors for advanced epithelial ovarian cancer(EOC).Methods We enrolled 241 patients with stage III and IV EOC who were diagnosed at the Yunnan Cancer Hospital between October 2006 and December 2015.The observation(NACT-IDS) group(n = 119) received 1–3 courses of platinum-based NACT,followed by interval debulking surgery(IDS) and 6–8 courses of postoperative chemotherapy.The control group underwent primary debulking surgery(PDS)(n = 122) followed by 6–8 courses of postoperative chemotherapy.We analyzed the general conditions of the operations and the survival of both groups.Results Operating time,intraoperative blood loss and postoperative hospitalization were significantly lower in the NACT-IDS group(P < 0.05).The rate of optimal cytoreductive surgery was significantly higher in the NACT-IDS group(P < 0.05).A visible residual lesion was observed in 49(41.18%) and 48(40%) cases in the NACT-IDS and PDS groups,respectively,which were not significantly different(P > 0.05).The percentage of International Federation of Gynecology and Obstetrics(FIGO) stage IV tumors and the recurrence rates were significantly higher in the NACT-IDS group(P < 0.05).The mortality rates were 45.19%(47/104) and 35.19%(38/108) in the NACT-IDS and PDS groups,respectively(P > 0.05).Progression-free survival was 23.75 ± 9.98 and 23.57 ± 12.25 months in the NACT-IDS and PDS groups,respectively(P > 0.05).Overall survival(OS) was 31.11 ± 15.66 and 29.63 ± 18.00 months in the NACTIDS and PDS groups,respectively(P > 0.05).Optimal cytoreductive surgery with or without residual lesion was an independent influencing factor for advanced EOC in multivariate analysis.OS of patients treated with ≥8 courses of chemotherapy was significantly longer than those treated with < 8 courses.Conclusion NACT could improve the intra-and postoperative conditions in advanced EOC patients.Although the percentage of FIGO stage IV cancer was significantly higher in the NACT-IDS group,the prognosis was similar in both the NACT-IDS and PDS groups,suggesting that NACT improves the clinical outcome of advanced EOC.Optimal cytoreductive surgery with no residual lesion is a long-term protective factor in advanced EOC.At least 8 courses of chemotherapy overall or ≥ 6 courses postoperatively improves the OS.

Primary ovarian cancer combined with primary fallopian tube cancer:A case report

BACKGROUND Low grade serous carcinoma of the ovary(LGSOC)is a rare type of epithelial ovarian cancer with a low incidence rate.The origin of ovarian cancer has always been a hot topic in gynecological oncology research,and some scholars believe that the origin of ovarian malignant tumors is the fallopian tubes.Primary fallopian tube cancer is the lowest incidence of malignant tumors in the female reproductive system.There are only a few reports in the literature,but the mortality rate is very high.But in clinical practice,fallopian tube cancer is very common,but in most cases,it is classified as ovarian cancer.CASE SUMMARY We report a 54 years old postmenopausal woman who was hospitalized with a lower abdominal mass and underwent surgical treatment.The final pathological confirmation was low-grade serous carcinoma of the right ovary and low-grade serous carcinoma of the left fallopian tube.No special treatment was performed after the surgery,and the patient was instructed to undergo regular follow-up without any signs of disease progression.CONCLUSION The prognosis of LGSOC is relatively good,over 80%of patients still experience disease recurrence.

miR-338-3p和MACC1基因在卵巢上皮性癌(EOC)组织中的表达及其意义

目的探讨微RNA-338-3p(miR-338-3p)和MET转录调剂因子MACC1在卵巢上皮性癌(epithelial ovariancancer,EOC)组织中的表达及其临床意义。方法采用实时荧光定量PCR技术检测20例正常卵巢组织、20例卵巢良性上皮性肿瘤组织和65例EOC组织中miR-338-3p和 MACC1 基因的表达情况,分析二者表达的相关性及其与EOC临床病理指标的关系,Log-rank和Cox回归分析影响EOC患者复发和死亡的危险因素,Kaplan-Meier法分析miR-338-3p和MACC1表达对EOC患者生存的影响。结果 EOC组织中miR-338-3p和 MACC1 基因的表达分别为0.331±0.038和0.774± 0.025 ,与正常卵巢组织和良性卵巢肿瘤组织中的表达差异有统计学意义( F=77.916,P<0.001;F=77.945,P <0.001),不同性质卵巢组织中miR-338-3p和MACC1的表达呈明显负相关( r=-0.968,P <0.001)。在EOC中,临床分期越晚、组织级别越高、有淋巴结转移的癌组织中miR-338-3p表达越低、MACC1表达越高。Log-rank单因素分析显示miR-338-3p低表达与EOC患者的复发( P =0.038,HR=4.139,95%CI:1.271~8.078)和死亡( P =0.008,HR=3.007,95%CI:1.217~7.431)相关。与其他患者相比,miR-338-3p低表达且MACC1高表达的EOC患者的总体生存率和无进展生存率最低(χ 2= 16.960,P=0.001;χ 2=18.930,P =0.000)。结论 miR-338-3p低表达和MACC1高表达可能与EOC患者预后不良相关,二者可能共同参与EOC的进展和复发。

PD-1基因多态性与EOC易感性及预后的关系

目的探讨程序性细胞凋亡蛋白1(PD-1)基因PD-1.1(rs36084323)与PD-1.5(rs2227981)多态性与卵巢上皮癌(EOC)易感性及预后的关系。方法收集2009年4月至2012年5月在山东省日照市中医医院接受治疗的116例卵巢上皮癌患者(Case组),另选取同期110例健康体检人员作为对照(Control组),收集两组对象的血液标本,采用RT-PCR法分析卵巢上皮癌患者PD-1基因PD-1.1和PD-1.5的多态性及其与预后的关系。结果 Case组PD-1.1基因型分布及等位基因频率与Control组比较差异均有统计学意义(χ~2值分别为7.785、7.970,P值分别为0.020、0.005)。Case组PD-1.5等位基因频率与Control组比较差异有统计学意义(χ~2=4.939,P=0.045)。PD-1.1基因分型与卵巢上皮癌患者临床分期、肿瘤分化程度均有关联(χ~2值分别为7.744、10.229,P值分别为0.021、0.006)。PD-1.1基因AA型、AG型及GG型3年和5年的复发率分别为70.27%、68.42%、36.36%和86.49%、80.70%、63.64%,三种基因型3年和5年的复发率差异均有统计学意义(χ~2值分别为11.634、8.218,P值分别为0.003、0.011)。PD-1.1基因AA型、AG型及GG型5年总生存率分别为18.92%、43.86%、54.55%,经Kaplan-Meier分析,三者差异有统计学意义(χ~2=9.111,P=0.011)。经Cox回归多因素分析显示,PD-1.1基因分型为卵巢上皮癌患者5年复发率和死亡率的危险因素(HR=2.709,95%CI:1.127~4.892,P=0.004)。结论 PD-1.1多态性位点中的G基因携带者可能明显降低卵巢上皮癌的患病风险。PD-1.5多态位点的C和T基因可能与卵巢上皮癌发病无关。PD-1.1多态位点可能与卵巢上皮癌患者临床预后有关。

紫杉醇+铂类新辅助化疗方案治疗EOC的疗效及其对ERCC1与BRCA1表达的影响

目的观察紫杉醇+铂类(TP/TC)新辅助化疗方案对原发性上皮性卵巢癌(EOC)患者的治疗效果及其对切除修复交叉互补基因1(ERCC1)与Bcl-2结合抗凋亡基因1(BRCA1)表达的影响。方法将我院2012年1月至2013年1月收治的32例肿瘤细胞减灭术前行TP/TC新辅助化疗的EOC患者作为观察组,41例肿瘤细胞减灭术前未化疗的EOC患者作为对照组,采用免疫组化技术检测两组患者病理组织中的ERCC1与BRCA1基因表达,并进行比较。结果观察组和对照组缓解(RR)率分别为65.63%(21/32)、60.98%(25/41),2年存活率分别为81.25%(26/32)、80.49%(33/41),差异均无统计学意义(P>0.05);观察组患者的ERCC1阳性率为100.00%(32/32),其中阳性高表达率为68.75%(22/32);BRCA1阳性率为81.25%(26/32),其中阳性高表达率为21.88%(7/32),两种基因阳性率和阳性高表达率均高于对照组[82.93%(34/41)、31.71%(13/41);53.66%(22/41)、2.44%(1/41)],差异均有统计学意义(P<0.05)。结论 TP/TC新辅助化疗方案对EOC患者ERCC1与BRCA1表达有明显影响,新辅助化疗可导致患者耐药率升高,因此建议新辅助化疗应有选择性。

KIAA1199 induces advanced biological behavior and development of ovarian cancer through activation of the IL-6/STAT3 pathway

Recently,abnormal expression of KIAA1199 has been detected in Epithelial Ovarian Cancer(EOC).However,the underlined anti-ovarian cancer mechanism of KIAA1199 remains to be enlightened.In our study,we performed to elucidate the effects of KIAA1199 on the advanced biological behavior of EOC cells through activation of the IL-6/STAT3 pathway.Confirmed by immunohistochemistry,KIAA1199 was highly expressed in ovarian borderline and malignant epithelial tumors.A retrospective analysis found that EOC patients with low expression of KIAA1199 had a significantly higher 5-year survival rate than those with high expression.Mechanistically,IL-6 was used to stimulate EOC cells,and the expression of KIAA1199,STAT3 and p-STAT3 increased after IL-6 stimulation.These results could show that KIAA1199 is transcriptionally activated by IL6/STAT3 pathway,thereby accelerating the deterioration of EOC.KIAA1199 could also be used as a poor prognosis factor and potential target in treatment.

YTHDF1和EIF3C在上皮性卵巢癌中的表达及临床意义

目的分析YTH结构域N6-甲基腺嘌呤RNA结合蛋白F1(YTHDF1)和真核翻译起始因子3C(EIF3C)在上皮性卵巢癌(EOC)中的表达及临床意义。方法回顾性分析2016年1月至2020年1月徐州医科大学附属医院初诊收治的130例EOC患者的临床资料,另选取同期因卵巢良性囊肿行手术治疗的70例患者的正常卵巢组织作为对照。采用实时荧光定量聚合酶链反应(RT-qPCR)检测组织中YTHDF1 mRNA和EIF3C mRNA表达水平。采用免疫组化染色检测组织中YTHDF1蛋白和EIF3C蛋白表达情况。采用Pearson相关分析探讨YTHDF1 mRNA与EIF3C mRNA表达水平的相关性。分析YTHDF1蛋白、EIF3C蛋白表达情况与EOC患者临床病理特征的关联性。采用Kaplan-Meier法绘制生存曲线。采用Cox回归分析EOC患者预后的影响因素。结果EOC组织中YTHDF1 mRNA、EIF3C mRNA表达水平高于正常卵巢组织,差异有统计学意义(P<0.05)。EOC组织中YTHDF1蛋白、EIF3C蛋白阳性表达率高于正常卵巢组织,差异有统计学意义(P<0.05)。Pearson相关分析结果显示,EOC组织中YTHDF1 mRNA与EIF3C mRNA表达呈正相关(r=0.802,P<0.001)。EOC组织中YTHDF1蛋白、EIF3C蛋白表达情况与肿瘤FIGO分期、病理分级、淋巴结转移情况具有显著关联性(P<0.05)。YTHDF1阴性患者的生存预后优于阳性患者(log-rank检验:χ^(2)=6.120,P=0.013)。EIF3C阴性患者的生存预后优于阳性患者(log-rank检验:χ^(2)=10.610,P=0.001)。Cox回归分析结果显示,FIGO分期Ⅲ期、病理分级Ⅲ级、淋巴结转移、较高的CA125水平以及YTHDF1蛋白、EIF3C蛋白阳性表达是EOC患者不良预后的独立危险因素。结论EOC组织中YTHDF1、EIF3C表达升高,与不良临床病理特征有关。YTHDF1和EIF3C是潜在的评估EOC预后的生物标志物。

脾脏联合胰尾切除在上皮性卵巢癌肿瘤细胞减灭术中的临床观察

目的探讨上皮性卵巢癌(epithelial ovarian cancer,EOC)肿瘤细胞减灭术中行脾脏联合胰尾切除的安全性和疗效。方法选取2015年12月至2022年9月在复旦大学附属中山医院和中国科学技术大学附属第一医院(安徽省立医院)EOC肿瘤细胞减灭术中接受脾脏联合胰尾切除的患者共17例,回顾性分析患者的临床特点、手术信息、术后并发症及生存随访。结果17例患者包括13例初治和4例复发EOC患者。术前影像提示脾门转移的患者有11例(64.7%),术中发现6例脾门及胰尾肿瘤转移。术后脾窝放置负压引流管,监测引流液淀粉酶,引流管移除中位时间为8(3~12)天。术后4例患者发生生化漏(A级胰瘘),3例发生B级胰瘘,无C级胰瘘。2例行经皮穿刺引流后好转,其余持续引流、生长抑素、抗生素治疗后好转,无围手术期死亡,术后恢复至化疗中位时间为17.5(13~37)天。中位随访时间为14(4~64)个月,中位无进展生存期为10(5~32)个月。结论脾脏联合胰尾切除术在EOC肿瘤细胞减灭术中可行,通过适当的防治措施,术后并发症胰瘘可控。

PET-CT评估晚期上皮性卵巢癌肿瘤负荷与肿瘤标志物HE4及CA125的相关性研究

目的本研究旨在探讨晚期高级别上皮性卵巢癌患者血清HE4和CA125浓度与2-[^(18)F]FDG PET/CT参数评估肿瘤负荷的相关性。方法纳入66例初治前接受2-[^(18)F]FDG PET/CT和血清肿瘤标志物测定的患者,计算全身代谢肿瘤体积(wb_MTV)和总病变糖酵解(wb_TLG),求出各VOI的MTV值。SUVmax阈值设置为40%(MTV40和TLG40)和50%(MTV50和TLG50)。此外,还定义了四个VOI亚型:腹膜癌病、腹膜后结节、膈上结节和远处转移。通过将相应的MTV值相加,计算每组的MTV和TLG。TLG也进行了同样的计算。结果wb_MTV、wb_TLG与血清CA125、HE4浓度显著相关。HE4与WB_MTV40的相关性最强(r=0.62,P<0.001)。HE4和CA125腹膜癌MTV40与肿瘤标志物的皮尔逊相关系数分别为0.61(P<0.0001)和0.29(P=0.02)。这些肿瘤标志物均未显示出与通过体积参数评估的腹膜外肿瘤负荷呈正相关。结论2-[^(18)F]FDGPET/CT体积参数是客观评估肿瘤负荷及其解剖分布的可行工具,这些结果支持了HE4和PET/CT在临床实践中改善患者分层的有效性。

上皮型钙黏蛋白在卵巢癌腹腔种植转移中的作用

卵巢癌是女性因癌症死亡的重要原因之一,其预后不良的主要原因是卵巢癌易短期内复发和转移。卵巢癌转移涉及细胞间连接、血管生成、肿瘤微环境等多个方面。研究发现,上皮型钙黏蛋白(E-cadherin)是卵巢癌转移过程中的重要影响因素,其可以通过改变细胞-细胞间黏附、促进血管生成、调节上皮-间质转化进程、促进肿瘤侵袭及浸润来参与卵巢癌的转移。详细阐述E-cadherin的结构及其在卵巢癌中的表达,并就卵巢癌的种植转移机制及Ecadherin在卵巢癌种植转移中的作用进行综述,以期为卵巢癌的复发监测及后续治疗提供新的思路。

Evaluation of whether serum tumor markers in patients with epithelial ovarian carcinoma change following chemotherapy

Background Phenotypic and genotypic heterogeneity is a known feature of many cancers.Whether serum tumor marker kinds vary and change following chemotherapy is still unclear.The aim of this study was to investigate whether there is a change in the expression of serum tumor markers following chemotherapy,and the potential clinical significance in patients with epithelial ovarian carcinoma （EOC） or primary serous peritoneal carcinoma （PSPC）.Methods Samples were collected before surgery,during chemotherapy and during follow-up for enzyme-linked immunosorbent assay （ELISA）-based evaluation of serum CA-125,CA19-9 and CP2 levels in patients with EOC or PSPC who had received primary debulking surgery followed by adjuvant chemotherapy.In total,72 patients were examined,including 37 patients with recurrent lesions and 35 patients receiving first-line chemotherapy.Results In 35 de novo patients,20% （7/35） demonstrated a significant changed serum tumor marker kinds among whom the patients with mucinous carcinoma （57.1%,4/7） showed resistance to chemotherapy.In the 37 recurrent patients,51.4% （19/37） had changed serum tumor markers,of whom 57.9% （11/19） presented with serous carcinoma.There was no significant difference in median progression-free survival or overall survival in patients with drug-sensitive or drug-resistant recurrence in patients with changed tumor marker kinds relative to those with unchanged markers.However,for patients with changed serum tumor markers there was a trend towards prolonged survival compared with the unchanged serum tumor marker group.In the 17 patients with secondary recurrence,37.5% （6/17） had changed tumor marker levels.The ratios of CA-125/CP2 and CA-125/CA19-9 were significantly different after either chemotherapy or recurrence.Conclusions Serum tumor marker expression in patients with EOC or PSPC may change after chemotherapy or recurrence,indicating that in addition to the markers that are abnormal before surgery,those markers that are normalshould also be monitored during chemotherapy and follow-up.

Clinical outcomes of fertility-sparing treatments in young patients with epithelial ovarian carcinoma

Objective:To assess the clinical outcomes of fertility-sparing treatments in young patients with epithelial ovarian carcinoma (EOC).Methods:A retrospective study of young EOC inpatients (≤40 years old) was performed during January 1994 and December 2010 in eight institutions.Results:Data were analyzed from 94 patients treated with fertility-sparing surgery with a median follow-up time of 58.7 months.As histologic grade increased,overall survival (OS) and disease-free survival (DFS) of patients receiving fertility-sparing surgery declined.Neither staging surgery nor laparoscopy of early stage EOC with conservative surgery had a significant effect on OS or DFS.Normal menstruation recommenced after chemotherapy in 89% of the fertility-sparing group.Seventeen pregnancies among twelve patients were achieved by the end of the follow-ups.Conclusions:Fertility-sparing treatment for patients with EOC Stage I Grade 1 could be cautiously considered for young patients.The surgical procedure and surgical route might not significantly influence the prognosis.Standard chemotherapy is not likely to have an evident impact on ovarian function or fertility in young patients.

辅助化疗对早期卵巢透明细胞癌生存的影响

目的:探讨术后辅助化疗对早期卵巢透明细胞癌(OCCC)生存的影响,确定影响早期OCCC生存预后的因素。方法:从SEER数据库中筛选2000年至2019年组织学诊断为早期OCCC的患者,使用倾向评分匹配控制化疗组及未化疗组间的混杂因素,使用Kaplan-Meier法及log-rank检验比较化疗组及未化疗组癌症特异性生存(CSS)的差异,Cox比例风险模型评估临床病理因素与CSS的相关性。结果:根据纳排标准筛选出2446例患者,中位年龄55岁(18~91岁),1772例(72.4%)患者接受术后化疗,674例(27.5%)患者未接受术后化疗。PSM后共有860例患者纳入分析,未化疗组5年CSS率为89.7%,化疗组5年CSS率为88.9%,差异无统计学意义(P=0.480)。分层分析显示,对于Ia/b期患者,化疗组5年CSS率为90.2%,未化疗组5年CSS率为92.1%,差异无统计学意义(P=0.638)。对于Ic期患者,化疗组5年CSS率为85.4%,未化疗组5年CSS率为87.1%,差异均无统计学意义(P=0.689)。单因素及多因素Cox回归分析显示,年龄>48岁、Ic期是影响CSS的危险因素,而术中淋巴结切除数>10枚为保护性因素。结论:I期OCCC患者术后是否辅助化疗,其生存结果相似,Ic期和年龄>48岁患者死亡风险增加,术中淋巴结清扫数量>10枚可降低患者死亡风险。

卵巢上皮性癌组织miR-143-3p、TIMELESS mRNA表达与患者临床病理特征及预后的关系

目的探讨卵巢上皮性癌(EOC)组织微小核糖核酸-143-3p(miR-143-3p)、永恒昼夜节律调节器(TIME⁃LESS)mRNA表达与患者临床病理特征、预后的关系。方法选取EOC患者106例,术中收集EOC组织及对应癌旁组织,用实时荧光定量聚合酶链反应检测miR-143-3p、TIMELESS mRNA。通过TargetScan、StarBase、miRWalk等在线数据库预测miR-143-3p与TIMELESS的结合位点,Pearson相关法分析miR-143-3p与TIMELESS mRNA表达的相关性。分析miR-143-3p、TIMELESS mRNA表达与EOC患者临床病理特征的关系。对EOC患者随访3年,统计累积生存率,根据miR-143-3p、TIMELESS mRNA相对表达量均值,将患者分为miR-143-3p、TIMELESS mRNA高/低表达者,Kaplan-Meier法绘制生存曲线,进行生存分析;多因素Cox回归分析miR-143-3p、TIMELESS表达对EOC患者预后的影响。结果与癌旁组织比较,EOC组织中miR-143-3p相对表达量低,TIMELESS mRNA相对表达量高(P均<0.05)。miR-143-3p与TIMELESS在3′-非翻译区1453~1460处存在结合位点。EOC组织中miR-143-3p表达与TIMELESS mRNA表达呈负相关(r=-0.748,P<0.05)。miR-143-3p、TIMELESS mRNA表达与肿瘤国际妇产科联盟(FIGO)分期、分化程度、淋巴结转移和远处转移有关(P均<0.05)。随访3年,106例EOC患者3年累积生存率为69.81%(74/106)。miR-143-3p高表达者3年累积生存率高于miR-143-3p低表达者(P<0.05),TIMELESS mRNA高表达者3年累积生存率低于TIMELESS mRNA低表达者(P<0.05)。影响EOC患者预后的独立危险因素为FIGO分期Ⅲ~Ⅳ期、低分化、淋巴结转移、远处转移、TIMELESS mRNA≥1.11(P均<0.05),独立保护因素为miR-143-3p≥0.97(P<0.05)。结论EOC组织miR-143-3p低表达、TIMELESS mRNA高表达,二者表达变化与EOC的FIGO分期、分化程度、淋巴结转移、远处转移和预后密切相关。

微卫星不稳定性在泌尿系统及妇科肿瘤中的研究进展

随着在越来越多的肿瘤中发现微卫星不稳定性(MSI)/错配修复缺陷存在,以及针对MSI阳性肿瘤患者的一类特殊免疫治疗药物——抗程序性死亡受体1或程序性死亡受体配体1免疫检查点抑制剂的使用,MSI已经成为预测肿瘤预后以及指导免疫治疗的一个非常重要的指标。本文主要综述MSI的发生机制、检测方法及其在泌尿系统、妇科常见肿瘤中的研究进展,为后续MSI的进一步研究提供参考。