Management of retroperitoneal high-grade serous carcinoma of unknown origin:A case report

BACKGROUND Retroperitoneal high-grade serous carcinoma(HGSC)of unknown origin is a sporadic tumor that can originate from ovarian cancer.Herein,we report the case of a woman with retroperitoneal HGSC of unknown origin and describe how she was diagnosed and treated.CASE SUMMARY A 71-year-old female presented with the tumor marker CA125 elevated to 1041.9 U/mL upon a regular health examination.Computed tomography revealed retroperitoneal lymph node enlargement.Subsequently,positron emission tomography scanning revealed lesions with increased F-18 fluorodeoxyglucose uptake at the nodes.As a result,she underwent laparoscopic lymph node resection,and pathology revealed metastatic adenocarcinoma with CK7(+),PAX8(+),WT1(+),PR(-),and p53 mutational loss of expression,indicating that the origin may be from the adnexa.The patient was admitted to our ward and underwent laparoscopic staging;however,the pathological results were negative.Under the suspicion of retroperitoneal HGSC of unknown origin,chemotherapy and targeted therapy were initiated.Tumor marker levels decreased after treatment.CONCLUSION We present a case of HGSC of unknown origin managed using retroperitoneal lymphadenectomy,staging surgery,chemotherapy,and targeted therapy.

High-grade serous carcinoma of the fallopian tube in a young woman with chromosomal 4q abnormality:A case report

BACKGROUND Few studies have reported an association between an increased risk of acquiring cancers and survival in patients with 4q deletion syndrome.This study presents a rare association between chromosome 4q abnormalities and fallopian tube highgrade serous carcinoma(HGSC)in a young woman.CASE SUMMARY A 35-year-old woman presented with acute dull abdominal pain and a known chromosomal abnormality involving 4q13.3 duplication and 4q23q24 deletion.Upon arrival at the emergency room,her abdomen appeared ovoid and distended with palpable shifting dullness.Ascites were identified through abdominal ultrasound,and computed tomography revealed an omentum cake and an enlarged bilateral adnexa.Blood tests showed elevated CA-125 levels.Paracentesis was conducted,and immunohistochemistry indicated that the cancer cells favored an ovarian origin,making us suspect ovarian cancer.The patient underwent debulking surgery,which led to a diagnosis of stage IIIC HGSC of the fallopian tube.Subsequently,the patient received adjuvant chemotherapy with carboplatin and paclitaxel,resulting in stable current condition.CONCLUSION This study demonstrates a rare correlation between a chromosome 4q abnormality and HGSC.UBE2D3 may affect crucial cancer-related pathways,including P53,BRCA,cyclin D,and tyrosine kinase receptors,thereby possibly contributing to cancer development.In addition,ADH1 and DDIT4 may be potential influencers of both carcinogenic and therapeutic responses.

Clinical Significance of Serum Galectin-1 and Its Tissue Immunohistochemical Expression in Serous Ovarian Carcinoma Patients

Objectives: Serous ovarian carcinoma (SOC) is the commonest ovarian carcinoma type with poor prognosis due to early metastasis and first presentation with advanced stage. In this work, we investigated serum level of Galactin-1 (Gal-1) and its tissue immunohistochemical expression in SOC patients at different stages trying to find out its significance as a diagnostic and prognostic marker. Patients and methods: The study included 95 females I-Control group: Twenty five healthy females;II-Patients group: Seventy females diagnosed as SOC at different stages;Stage I: 8 cases, Stage II: 12 cases, Stage III: 32 cases and Stage VI:18 cases. Serum Galectin-1 and CA-125 were measured by ELIZA and tissue Galectin-1 was assessed by immunohistochemistry. All patients were followed for up to 3 years after surgery. Results: Serum Gal-1 and CA-125 levels were significantly higehr in SOC patients compared to controls (p 0.001). We found a direct positive statistically significant correlation between serum Gal-1 and CA125 levels (p 0.001). Serum Gal-1 at cut off value > 135 ng/ml was superior to CA-125 a cut off value > 49 u/ml with sensitivity, specificity of 100%, vs 88.57, 96% for CA-125. Serum Gal-1 was significantly associated with tumor stage (p 0.001). Immunohistochemistry showed that patients with strong Gal-1 expression had higher serum level (p = 0.002). Stromal and tumor Gal-1 expression were significantly correlated with tumor grade (p 0.001) and stage (p = 0.001). Serum Gal-1, CA-125 and IHC Gal-1 expression were associated with poor survival (p 0.001, p = 0.009 and p = 0.002) respectively. Conclusion: Serum Gal-1 and its tissue IHC expression are useful diagnostic and prognostic markers for SOC patients.

Rescue of p53 functions by in vitro-transcribed mRNA impedes the growth of high-grade serous ovarian cancer

Background:The cellular tumor protein p53(TP53)is a tumor suppressor gene that is frequently mutated in human cancers.Among various cancer types,the very aggressive high-grade serous ovarian carcinoma(HGSOC)exhibits the high-est prevalence of TP53 mutations,present in>96%of cases.Despite intensive efforts to reactivate p53,no clinical drug has been approved to rescue p53 func-tion.In this study,our primary objective was to administer in vitro-transcribed(IVT)wild-type(WT)p53-mRNA to HGSOC cell lines,primary cells,and ortho-topic mouse models,with the aim of exploring its impact on inhibiting tumor growth and dissemination,both in vitro and in vivo.Methods:To restore the activity of p53,WT p53 was exogenously expressed in HGSOC cell lines using a mammalian vector system.Moreover,IVT WT p53 mRNA was delivered into different HGSOC model systems(primary cells and patient-derived organoids)using liposomes and studied for proliferation,cell cycle progression,apoptosis,colony formation,and chromosomal instabil-ity.Transcriptomic alterations induced by p53 mRNA were analyzed using RNA sequencing in OVCAR-8 and primary HGSOC cells,followed by ingenuity path-way analysis.In vivo effects on tumor growth and metastasis were studied using orthotopic xenografts and metastatic intraperitoneal mouse models.Results:Reactivation of the TP53 tumor suppressor gene was explored in differ-ent HGSOC model systems using newly designed IVT mRNA-based methods.The introduction of WT p53 mRNA triggered dose-dependent apoptosis,cell cycle arrest,and potent long-lasting inhibition of HGSOC cell proliferation.Transcriptome analysis of OVCAR-8 cells upon mRNA-based p53 reactivation revealed significant alterations in gene expression related to p53 signaling,such as apoptosis,cell cycle regulation,and DNA damage.Restoring p53 function concurrently reduces chromosomal instability within the HGSOC cells,under-scoring its crucial contribution in safeguarding genomic integrity by moderating the baseline occurrence of double-strand breaks arising from replication stress.Furthermore,in various mouse models,treatment with p53 mRNA reduced tumor growth and inhibited tumor cell dissemination in the peritoneal cavity in a dose-dependent manner.Conclusions:The IVT mRNA-based reactivation of p53 holds promise as a potential therapeutic strategy for HGSOC,providing valuable insights into the molecular mechanisms underlying p53 function and its relevance in ovarian cancer treatment.

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.

Characterization of candidate factors associated with the metastasis and progression of high-grade serous ovarian cancer

Background:High-grade serous ovarian cancer(HGSOC)is the biggest cause of gynecological cancer-related mortality because of its extremely metastatic nature.This study aimed to explore and evaluate the characteristics of candidate factors associated with the metastasis and progression of HGSOC.Methods:Transcriptomic data of HGSOC patients’samples collected from primary tumors and matched omental metastatic tumors were obtained from three independent studies in the National Center for Biotechnology Information(NCBI)Gene Expression Omnibus(GEO)database.Differentially expressed genes(DEGs)were selected to evaluate the effects on the prognosis and progression of ovarian cancer using data from The Cancer Genome Atlas(TCGA)database.Hub genes’immune landscapes were estimated by the Tumor Immune Estimation Resource(TIMER)database.Finally,using 25 HGSOC patients'cancer tissues and 10 normal fallopian tube tissues,immunohistochemistry(IHC)was performed to quantify the expression levels of hub genes associated with International Federation of Gynecology and Obstetrics(FIGO)stages.Results:Fourteen DEGs,ADIPOQ,ALPK2,BARX1,CD37,CNR2,COL5A3,FABP4,FAP,GPR68,ITGBL1,MOXD1,PODNL1,SFRP2,and TRAF3IP3,were upregulated in metastatic tumors in every database while CADPS,GATA4,STAR,and TSPAN8 were downregulated.ALPK2,FAP,SFRP2,GATA4,STAR,and TSPAN8 were selected as hub genes significantly associated with survival and recurrence.All hub genes were correlated with tumor microenvironment infiltration,especially cancer-associated fibroblasts and natural killer(NK)cells.Furthermore,the expression of FAP and SFRP2 was positively correlated with the International Federation of Gynecology and Obstetrics(FIGO)stage,and their increased protein expression levels in metastatic samples compared with primary tumor samples and normal tissues were confirmed by IHC(P=0.0002 and P=0.0001,respectively).Conclusions:This study describes screening for DEGs in HGSOC primary tumors and matched metastasis tumors using integrated bioinformatics analyses.We identified six hub genes that were correlated with the progression of HGSOC,particularly FAP and SFRP2,which might provide effective targets to predict prognosis and provide novel insights into individual therapeutic strategies for HGSOC.

朊蛋白与p53突变在卵巢浆液性癌组织中表达的相关性及预后意义

目的:探讨卵巢浆液性癌组织中朊蛋白表达水平及其与p53突变的相关性。方法:选取2012年11月10日至2019年10月30日北京大学第三医院妇产科收治的Ⅰ~Ⅳ期卵巢浆液性癌139例,同时选取20例正常卵巢组织、20例卵巢良性肿瘤组织作为对照。免疫组化、p53突变测序法检测朊蛋白表达水平及p53突变类型。结果:朊蛋白在卵巢浆液性癌组织中阳性表达率明显高于卵巢良性肿瘤组织和正常卵巢组织,差异均有统计学意义(59%vs 30%、20%,P分别为0.034、0.003)。卵巢浆液性癌中p53突变率高达84.89%(118/139),主要位于第5外显子(29.66%,35/118)以及DNA结合域的热点突变位点(50.84%,60/118);朊蛋白高表达组中p53构象突变率为71.93%(41/57),显著高于朊蛋白低表达组(45.90%,28/61),差异有统计学意义(P=0.004)。p53构象突变与卵巢浆液性癌淋巴结转移(P=0.005)及耐药(P=0.009)密切相关。p53构象突变患者的平均疾病无进展生存期[(34.99±2.72)月vs(43.01±2.35)月,P=0.036]及平均总生存期[(47.94±3.40)月vs(56.00±2.89)月,P=0.049]均低于p53接触突变患者。结论:卵巢浆液性癌组织中朊蛋白呈高表达,并与p53构象突变相关。p53构象突变与卵巢浆液性癌不良预后相关。

MCM5在卵巢癌中的作用及机制分析

目的探讨MCM5在卵巢癌中的表达、作用机制和临床意义。方法利用GEO、TCGA等数据库分析MCM5 mRNA在卵巢癌中的表达与预后关系;采用免疫组化SP两步法染色分析卵巢癌中MCM5的表达;应用CCK-8法、EDU、平板克隆、Transwell小室和流式细胞术检测MCM5对细胞增殖、迁移侵袭和凋亡的影响。结果生物信息学分析发现MCM5在卵巢癌中mRNA水平明显升高,且高表达者无进展生存期短(P<0.01)。免疫表型:MCM5在输卵管上皮中不表达(0/6),在卵巢癌中阳性率为48.3%(57/118),MCM5在卵巢癌中的表达显著高于输卵管上皮,在高级别浆液性癌中呈弥漫强表达,MCM5^(+)与ER-、Ki67增殖指数高相关。敲低MCM5的表达,抑制卵巢癌细胞增殖(P<0.05)、克隆形成(P<0.05)、侵袭和迁移(P<0.05),促进凋亡。结论MCM5在卵巢癌细胞和组织中表达升高,与预后不良相关,有望成为治疗卵巢癌的新靶标。

卵巢浆液性癌中miR-182和E-cadherin的表达及意义

目的检测卵巢浆液性癌中微小RNA-182(microRNA-182,miR-182)和上皮型粘附素(E-cadherin)的表达,探讨其相关性及临床意义。方法选择行卵巢浆液性癌根治性手术的患者59例作为研究组,选择行手术治疗的卵巢浆液性囊腺瘤患者59例作为对照组,应用实时荧光定量PCR法检测组织中miR-182的表达,应用免疫组化法检测组织E-cadherin的表达。结果研究组中miR-182的表达量(1.83±0.32)明显高于对照组(1.31±0.31)(t=4.59,P=0.012),研究组中E-cadherin表达阳性率(47.46%)明显低于对照组(84.75%)(X~2=18.31,P=0.000)。miR-182和E-cadherin在卵巢浆液性癌不同级别(2.01±0.29 vs.1.66±0.22)(27.59%vs.66.67%)、不同肿瘤最大径(1.93±0.22 vs.1.64±0.39)(28.21%vs.85.00%)及有无脉管癌栓(1.80±0.15 vs.2.03±0.20)(20.00%vs.53.06%)的比较中差异有统计学意义(P<0.05),而在不同年龄、有无淋巴结转移分组的比较中差别无统计学意义(P>0.05)。线性相关分析显示研究组中miR-182与E-cadherin呈负相关性(r=-0.57,P=0.008)。生存分析显示miR-182的表达与患者生存时间有关(P<0.05)。结论miR-182和E-cadherin在卵巢浆液性癌中异常表达且具有相关性,组织中miR-182高表达提示不良预后。

血清CA125和HE4的动态变化在预测卵巢高级别浆液性腺癌无进展生存期方面的价值研究

目的:研究血清糖类抗原125(carbohydrate antigen 125,CA125)和人附睾蛋白4(human epididymal protein 4,HE4)在术前以及术后化疗过程中的动态变化与卵巢癌患者无进展生存期(progression-free survival,PFS)及铂敏感性之间的关系。方法:回顾性分析上海交通大学医学院附属第一人民医院妇科肿瘤病房收治的经过规范化治疗的卵巢癌患者术前、术后化疗前,以及化疗中至少2次血清CA125及HE4水平,并收集对铂类药物敏感性、PFS等数据。主要统计学方法包括卡方检验、t检验、方差分析和Logistic回归分析及Cox比例风险回归分析等。结果:对117例卵巢高级别浆液性腺癌患者的分析结果提示,CA125和HE4阳性与肿瘤较高期别、多腹水量、不满意减灭、腹水细胞学阳性相关。通过Cox回归分析验证得出CA125和HE4均是预后的危险因素(OR=4.29,P=0.010;OR=1.77,P=0.049)。CA125、HE4均阳性患者组与仅CA125阳性的患者组比较,预后差异无统计学意义(P>0.05)。根据公式t_(1/2)=t_(1)/[2×lg(c_(1)/c_(2))]计算CA125和HE4半衰期,截取术前CA125和HE4、术后CA125和HE4最低值、CA125和HE4半衰期的最优cut-off值,分别为436 U/L和400 pmol/L、12 U/L和35 pmol/L、21 d和25 d,预后分析提示除了HE4最低值与预后无关,其余均和预后相关,其中CA125半衰期>21 d的HR值最高为3.28,中位PFS下降57.5%(P<0.001)。通过绘制受试者工作特征曲线计算曲线下面积(area under the curve,AUC),CA125半衰期>21 d(AUC=0.76)、CA125最低值>12 U/L(AUC=0.70)及第3程化疗后CA125未回归正常(AUC=0.71)这3项指标对于预测存在3年内复发有一定的临床价值,其灵敏度分别为71.8%、68.3%、68.2%,特异度分别为79.6%、71.7%、72.6%。结论:CA125半衰期、CA125化疗过程中最低值、第3程化疗后CA125未回归正常及6项指标中≥2项阳性这4个指标对于预测存在3年内复发有一定的临床价值,而对于预测铂敏感性的价值有待进一步探索。

长链非编码RNA LINC00641调控卵巢浆液性癌细胞增殖的探究

目的探讨长链非编码RNA LINC00641(long noncoding RNA LINC00641,LINC00641)在卵巢浆液性癌中的表达,探讨其对细胞增殖的调控作用。方法应用GEPIA数据库预测LINC00641在卵巢癌中表达的趋势。选择57例卵巢浆液性癌组织作为观察组,选择57卵巢浆液性囊腺瘤组织作为对照组,应用实时荧光定量PCR(quantitative real time PCR,qRT-PCR)法检测LINC00641的表达,应用免疫组化法检测Ki67的表达。选择人卵巢浆液性癌SKOV3细胞系和人卵巢表面上皮细胞HOSEpiC细胞系,应用qRT-PCR检测LINC00641的表达,转染过表达LINC00641质粒建立SKOV3细胞的OE-LINC00641组,并设立未行任何转染的空白对照组(NC)。应用CCK-8检测细胞增殖活性。结果GEPIA数据库显示LINC00641在卵巢癌中的表达有下调趋势(P<0.05)。组织学实验显示卵巢浆液性癌组织中LINC00641的表达量(1.325±0.115)明显低于对照组(1.665±0.147)(t=6.24,P<0.05),LINC00641在不同病变分级(1.31±0.11 vs 1.43±0.09)和肿瘤最大径(1.25±0.11 vs 1.36±0.10)的比较中差异有统计学意义(P<0.05),卵巢浆液性癌中LINC00641和Ki67增殖指数具有负相关性(P<0.05)。体外细胞培养实验显示SKOV3中LINC00641的表达量(1.33±0.13)明显低于HOSEpiC(1.89±0.24)(P<0.05)。OE-LINC00641组细胞增殖活性明显低于NC组(P<0.05)。结论LINC00641在卵巢浆液性癌中低表达,对肿瘤细胞增殖有抑制作用。

P2RX1对浆液性卵巢癌患者的预后判断价值及其在免疫浸润机制中的作用

目的:探讨嘌呤能受体X1(P2RX1)与浆液性卵巢癌(OV)患者的临床病理指标及肿瘤微环境免疫细胞浸润的关系,为OV免疫治疗提供新的线索。方法:以OV患者的血清和卵巢癌组织为研究对象,分别以健康成年人和非癌症患者为对照,采用免疫组织化学(IHC)、逆转录荧光定量PCR(RT-qPCR)、酶联免疫吸附试验(ELISA)及生物信息学方法研究OV中P2RX1的表达模式。利用TCGA数据库分析P2RX1 mRNA的表达水平与OV患者不同临床病理指标的相关性;筛选差异基因,分析OV中P2RX1参与的信号通路及其生物学功能;分析P2RX1与免疫细胞浸润丰度、肿瘤免疫相关基因、免疫检查点等的相关性。结果:IHC检测结果显示,P2RX1主要表达于正常卵巢上皮中;RT-qPCR检测结果显示,与非癌组织相比,P2RX1 mRNA在OV中低表达(P<0.05);ELISA分析结果显示,与正常对照血清相比,P2RX1蛋白在OV患者血清中低表达(P<0.05)。检索TCGA数据库,结果显示高表达P2RX1的OV患者总生存期较长,预后较好(P<0.05)。P2RX1与OV患者的肿瘤纯度和年龄有关(P<0.05)。富集分析结果显示不同P2RX1表达水平的OV患者其差异表达基因主要富集于免疫细胞分化、发育等生物学进程。P2RX1与OV中TGFB1、SLAMF7、CD27等多个免疫检查点有关。P2RX1与B细胞标记包括CD79A、CD79B、CD19明显正相关(均为r>0.4,P<0.05)。结论:在OV中P2RX1的低表达与患者预后不良有关,P2RX1可能参与OV肿瘤微环境免疫细胞浸润、分化等进程。

卵巢子宫内膜样癌与高级别浆液性癌的MRI鉴别诊断

目的:比较卵巢子宫内膜样癌(OEC)与高级别浆液性癌(HGSC)的MRI特征,为两者的术前鉴别诊断提供依据。方法:回顾性选取2017年1月—2023年11月来宾市人民医院收治的24例OEC和49例HGSC患者,术前已行MRI影像检查并经临床手术病理证实,比较其临床特征及MRI特征并总结分析。结果:2种癌症的肿瘤标志物水平、有无贫血、肿瘤最大径差异均无统计学意义(P>0.05);而2种癌症的患者发病年龄、FIGO分期、单双侧发病、边界、实性部分最大径、肿瘤囊实性分布特点、囊性T_(1)WI信号、实性部分强化特点、实性成分DWI高b值信号特点、大量腹水发生率、淋巴结转移及腹膜种植转移、合并子宫内膜病变,差异均有统计学意义(P<0.05)。结论:OEC典型表现为大单囊伴“梳妆”乳头样偏心附壁肿块为主、囊内伴或不伴纤维分隔;HGSC表现以实性占比为主的多房囊实性肿块伴多发纤维分隔并可能双侧癌。

卵巢子宫内膜样癌与高级别浆液性癌临床及MRI特征的对照分析

目的:探讨卵巢子宫内膜样癌(OEC)与高级别浆液性癌(HGSC)的临床及MRI特征表现,评价MRI对OEC与HGSC的鉴别诊断价值。方法:回顾性分析经手术病理证实的12例OEC患者(OEC组)及22例HGSC患者(HGSC组)的临床资料及MRI特征表现。临床资料包括患者年龄、体征、绝经状态、实验室检查、有无合并子宫内膜异位症等。MRI特征表现包括肿瘤形态、偏侧性、壁结节形态、囊性灶多寡特点、囊性成分信号特征、实性成分强化方式、肿瘤有无包膜、双发癌灶(合并子宫内膜癌)、腹膜种植、淋巴结转移及腹水情况等。结果:OEC与HGSC在肿瘤偏侧性、囊性灶多寡特点、部分囊性成分T1WI高信号、壁结节形态、双发癌及腹膜种植转移的组间差异均有统计学意义(均P<0.05)。相较于HGSC,OEC形态较规则,大多单侧发病,单囊为主,部分囊性成分T1WI高信号,壁结节较光滑,双发癌相对多见,腹膜种植转移相对少。结论:OEC与HGSC的病灶偏侧性、囊性灶多寡特点、部分囊性成分T1WI高信号、壁结节形态及双发癌等MRI特征表现存在差异,有助于两者的鉴别诊断。

昼夜节律基因Bmal1在卵巢浆液性癌发生发展中的作用

目的 探讨节律基因Bmal1在卵巢癌发生、发展的作用。方法 收集2020年9月至2022年2月经山西医科大学第一医院病理确诊的卵巢浆液性癌病例,分为节律异常组和节律正常组,各30例。检测Bmal1、p53(突变型)、Vimentin在卵巢浆液性癌中的表达,采用实时荧光定量PCR技术(real-time quantitative PCR, RT-qPCR)和蛋白印迹法(Western blot)分别检测两组患者肿瘤组织中Bmal1 mRNA和蛋白的表达,用免疫组织化学法(immunohistochemistry, IHC)检测患者肿瘤组织中p53(突变型)蛋白、Vimentin蛋白的表达,并运用Image-ProPlus软件分析表达强度。运用χ2检验分析节律和临床病理特征的关系。运用Spearman相关性分析Bmal1蛋白和p53(突变型)蛋白、Bmal1蛋白和Vimentin蛋白的表达相关性。结果 节律异常组患者肿瘤组织中Bmal1 mRNA和蛋白的表达低于节律正常组(P<0.000 1),p53(突变型)MOD值和Vimentin MOD值高于节律正常组(P<0.001)。节律异常组高级别卵巢浆液性癌(high grade serous ovarian carcinoma, HGSOC)所占比例、Ⅲ+Ⅳ期者所占比例、有淋巴结转移者所占比例均高于节律正常组(P<0.05);两组<55岁人数所占比例差异无统计学意义。Bmal1 mRNA和蛋白在HGSOC、Ⅲ+Ⅳ期、有淋巴结转移患者中表达分别低于在低级别卵巢浆液性癌(low grade serous ovarian carcinoma, LGSOC)、Ⅰ+Ⅱ期、无淋巴结转移患者中表达(P<0.001);Bmal1 mRNA和蛋白在<55岁和≥55岁患者中表达量差异无统计学意义。Spearman相关性分析显示:Bmal1蛋白和p53(突变型)蛋白表达呈负相关;Bmal1蛋白和Vimentin蛋白表达呈负相关。结论 生物钟节律可以影响Bmal1的表达,Bmal1与卵巢癌患者预后相关。

JAK/STAT信号通路在卵巢高级别浆液性癌中的激活及预后意义

目的:Janus激酶(Janus kinase,JAK)、信号转导和转录活化因子(signal transducers and activators of transcription,STAT)构成的JAK/STAT信号通路的活化与卵巢高级别浆液性癌(high-grade serous carcinoma,HGSC)的预后和靶向治疗密切相关。本研究力求通过简单易行的检测手段,评估JAK/STAT信号通路的活化在卵巢HGSC中的预后意义。方法:运用免疫组织化学染色方法,对73例卵巢HGSC的病理切片进行磷酸化STAT3(pSTAT3)和磷酸化STAT5(pSTAT5)染色,并对二者的染色强度及染色范围进行定量评估。以此为标准,将HGSC病例分为pSTAT3低/高表达组以及pSTAT5低/高表达组,并对不同分组的患者预后情况进行分析,探究pSTAT3和pSTAT5的表达与HGSC预后的关系。结果:部分卵巢HGSC存在pSTAT3和pSTAT5蛋白的高表达,且二者的表达与HGSC的预后相关。pSTAT3和pSTAT5蛋白的表达水平在预后较好组(生存期≥3年)和预后较差组(生存期<3年)中的差异有统计学意义,伴有pSTAT3高表达、或pSTAT5高表达、或pSTAT3和pSTAT5皆高表达的HGSC病例预后更差,表现为疾病无进展生存期以及总生存期均显著低于对应的低表达组(P<0.001)。结论:通过pSTAT3、pSTAT5蛋白的免疫组织化学染色,可以实现对卵巢HGSC患者进行风险评估,可协助判断预后同时筛选高危人群,为STAT抑制剂及抗血管生成药物的适用人群提供有益的参考指标。

卵巢低级别浆液性癌患者的临床特点分析

目的:探讨卵巢低级别浆液性癌患者的临床和治疗特点。方法:回顾分析2010年1月至2020年6月在北京大学人民医院妇科接受治疗的44例卵巢低级别浆液性癌患者的病历资料,包括发病年龄、肿瘤分期、初始手术、一线化疗、新辅助化疗、内分泌治疗、复发治疗等数据。使用Kaplan-Meier生存曲线分析患者的无进展生存时间和总生存时间。结果:患者中位诊断年龄38岁,初诊时Ⅲ期最常见(52.3%)。初始治疗以手术联合含铂辅助化疗为主,晚期患者初次肿瘤细胞减灭术的无肉眼残留率为63.2%,79.0%达到满意减瘤术;6例行新辅助化疗,客观缓解率为83.3%(5/6),5例行间歇性肿瘤细胞减灭术,均无残留病灶。初始治疗后42例病情完全或部分缓解。14例(33.3%)出现至少1次复发,第1次复发以手术为主,辅以铂类化疗和内分泌治疗。中位随访时间73.0个月,初治后中位无进展生存时间83.0个月,5年生存率85.2%,中位总生存时间未达到。结论:卵巢低级别浆液性癌多在中青年发病,Ⅲ期最常见。无论初治和复发患者,手术治疗最重要,应以无残留病灶为目标。一线化疗方案仍是铂类为基础的联合方案,尽管化疗相对耐药,晚期患者也可考虑新辅助化疗,内分泌治疗有重要地位,总体预后好于卵巢高级别浆液性癌。

液基细胞学联合细胞蜡块免疫组化技术在卵巢浆液性癌腹腔积液诊断中的应用

目的:分析液基细胞学联合细胞蜡块免疫组化技术对卵巢浆液性癌腹腔积液的诊断价值。方法:120例卵巢浆液性癌患者腹腔积液标本,均行传统细胞学涂片、液基细胞学制片技术、细胞蜡块免疫组化技术以及液基细胞学联合细胞蜡块免疫组化技术检测浆液性癌细胞,比较各种检测方法的诊断结果。结果:液基细胞学联合细胞蜡块免疫组化技术浆液性癌细胞检出率93.3%,高于传统细胞学涂片技术(55.0%)、液基细胞学涂片技术(76.7%)及细胞蜡块免疫组化技术(87.5%),差异均具有统计学意义(P<0.001)。结论:液基细胞学联合细胞蜡块免疫组化技术简单、易行,可以极大提高腹腔积液中卵巢浆液性癌细胞的检出率,有助于临床判断肿瘤恶性程度,制定治疗方案,值得临床推广应用。

CT纹理分析在卵巢透明细胞癌与高级别浆液性囊腺癌鉴别诊断中的价值

目的探讨CT纹理分析在鉴别卵巢透明细胞癌(ovarian clear cell carcinoma,OCCC)与高级别卵巢浆液性囊腺癌(high-grade ovarian serous cystadenocarcinoma,HGSC)中的价值。方法回顾性分析2020年1月-2022年4月在潍坊市人民医院住院治疗且经病理证实、临床资料完整的卵巢透明细胞癌患者23例及高级别浆液性囊腺癌患者35例。利用Image J软件测量并记录CT平扫期、动脉期、静脉期、延迟期四个时期的纹理参数,包括直方图参数(均值、标准差、偏度、峰度)及灰度共生矩阵参数(能量、对比、相关、逆差距、熵),比较两组间纹理参数的差异。采用两独立样本t检验或Mann-Whitney U检验对各参数统计分析,对差异有统计学意义的纹理参数进行ROC曲线分析,以判断其鉴别诊断效能。结果平扫期均值、标准差、偏度在两组间比较差异有统计学意义(P<0.05),且OCCC组均值、标准差小于HGSC组,OCCC组偏度大于HGSC组;峰度、能量、对比、相关、逆差距、熵差异无统计学意义(P>0.05)。动脉期均值、标准差在两组间比较差异有统计学意义(P<0.05),且OCCC组均值、标准差小于HGSC组;偏度、峰度、能量、对比、相关、逆差距、熵差异无统计学意义(P>0.05)。静脉期均值、偏度在两组间比较差异有统计学意义(P<0.05),且OCCC组均值小于HGSC组,OCCC组偏度大于HGSC组;标准差、峰度、能量、对比、相关、逆差距、熵差异无统计学意义(P>0.05)。延迟期均值、偏度在两组间比较差异有统计学意义(P<0.05),且OCCC组均值小于HGSC组,OCCC偏度大于HGSC组;标准差、峰度、能量、对比、相关、逆差距、熵差异无统计学意义(P>0.05)。其中诊断效能最佳者是平扫期均值,AUC=0.881(P<0.001),敏感度为65.22%,特异度为97.14%。结论CT纹理分析有助于鉴别卵巢透明细胞癌与高级别浆液性囊腺癌,可以为临床及影像诊断提供重要参考价值。

国际妇产科联盟Ⅳ期卵巢高级别浆液性癌患者远期生存情况及相关影响因素分析

目的探讨国际妇产科联盟(FIGO)Ⅳ期卵巢高级别浆液性癌患者的远期生存情况和相关影响因素。方法回顾性分析2010年1月至2020年12月于北京大学肿瘤医院接受初治Ⅳ期卵巢高级别浆液性癌患者的临床资料。根据治疗方式不同,将患者分为初始肿瘤细胞减灭术(PDS)组、中间型肿瘤细胞减灭术(IDS)组和单纯化疗组。分析患者的总生存期以及相关影响因素。结果本研究共纳入125例患者,其中PDS组21例、IDS组91例、单纯化疗组13例。3组年龄、糖类抗原125水平比较差异均有统计学意义(均P<0.05);PDS组与IDS组手术复杂性评分、上腹部手术比例比较差异均有统计学意义(均P<0.05)。PDS组中位总生存期70个月、IDS组中位总生存期56个月、单纯化疗组中位总生存期25个月,3组总生存期比较差异有统计学意义(P<0.001)。基于FIGO分期的分层分析结果显示,ⅣA期患者中位总生存期短于ⅣB期患者(49个月比59个月,P=0.013)。多因素Cox分析结果显示,初始治疗方式、应用聚腺苷二磷酸核糖聚合酶(PARP)抑制剂及术后肿瘤残留是Ⅳ期卵巢高级别浆液性癌患者总生存期的独立影响因素(均P<0.05)。结论肿瘤细胞减灭术可改善Ⅳ期卵巢高级别浆液性癌患者的预后,初始治疗方式、应用PARP抑制剂及术后肿瘤残留是总生存期的独立影响因素。