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.

Incidental Serous Tubal Intraepithelial Carcinoma Detected by a Surgery for Ectopic Pregnancy

Serous tubal intraepithelial carcinoma is a putative precursor of high-grade serous carcinoma, which is the most common histological type of ovarian or pelvic peritoneal cancer. Serous tubal intraepithelial carcinoma is commonly found in patients with breast cancer susceptibility gene mutations who undergo risk-reducing salpingo-oophorectomy. Incidental serous tubal intraepithelial carcinoma found by a non-prophylactic surgery is rare. A 33-year-old woman referred to our hospital for a diagnosis of ectopic pregnancy. She underwent a laparoscopic right salpingectomy. Pathologically, ectopic pregnancy in the ampulla of the right fallopian tube was confirmed and serous tubal intraepithelial carcinoma was observed in the fallopian tube. Subsequently, she underwent a laparoscopic hysterectomy, bilateral oophorectomy, and left salpingectomy as additional treatment. She has experienced no recurrence thus far for 37 months since the surgery.

Papillary serous carcinoma of the uterine cervix:a clinicopathological analysis of 4 cases and a literature review

Objective To investigate the clinicopathological characteristics and clinical treatment outcomes of patients with papillary serous carcinoma of the uterine cervix(PSCC).Methods In this study, 4 patients with histologically confirmed papillary serous carcinoma of the uterine cervix were retrospectively investigated. Pap smears, human papillomavirus(HPV) screening, tumor marker status, biopsy analysis, and relevant imaging examinations were conducted for the confirmation of primary diagnosis and recurrence. Patients underwent surgery, chemotherapy, or radiotherapy, and survival were the main endpoint.Results The 4 patients were diagnosed with IB1, IB1, IIA, or IIIB disease. Two patients(2/4) presented with recurrence within 18 months after primary therapy. Compared with chemotherapy alone(progressionfree survival(PFS): 11 months), radiotherapy combined with adjuvant chemotherapy showed favorable PFS rates(PFS: 20, 36, 13 months in 3 cases), although valid statistical analysis was not feasible because of the small sample size. The 5-year survival rate was 0%, and the 3-year survival rate was 75%. Our data, in agreement with the literature evidence, showed that the number of moderate-risk and high-risk factors in patients diagnosed with PSCC at an early stage was higher than that in patients diagnosed with common adenocarcinoma/squamous carcinoma of the uterine cervix.Conclusion PSCC has a poor clinical prognosis, and compared with chemotherapy alone, radiotherapy combined with adjuvant chemotherapy may lead to improved PFS.

Uterine papillary serous carcinoma: Its clinical and fundamental studyUterine papillary serous carcinoma: Its clinical and fundamental study

Uterine papillary serous carcinoma(UPSC) was established as a distinct type of endometrial carcinoma by Lauchlan in 1981 and Hendrickson et al in 1982, and ac- counted for 1 % - 10% of endometrial cancers. The occurrencer of papillary patterns of en- dometrial adenocarcinoma had been reportedly recognized since 1900, while until the late 1970s several authors have had described a variant of papillary endometrial cancer. UPSC is a morphologically unique variant of endometrial carcinoma that is pathologically defined by the presence of high nuclear grade, distinct papillary architechtural changes, psammoma bodies, and extensive lymph - vascular space invasion. CA125 is often mentioned a useful tumor marker either for diagnosis before starting treatment or in monitoring recurrence. The optimal treatment of UPSC is controversial and appears to be dependent upon the stage of the disease. Primary surgery comprised of TAH/BSO and complete staging is the mainstay of treatment. The patients with recurrent UPSC in many studies were treated with various combinations of surgery , radiation therapy, and chemotherapy. The molecular basis for the gneeral poor response of UPSC to adjuvant chemotherapy and radiotherapy is not well under- stood. UPSC tumors are more often aneuploid and contain overexpressed mutant p53 protein as compared to endometrioid adenocarcinoma. Unlike patients with adenocarcinoma of the endometrium, women with UPSC were less likely to be obese, hypertensive, or diabetic.

Coexistence of tuberculous peritonitis and primary papillary serous carcinoma of the peritoneum:A case report and review of the literature

A major diagnostic challenge to the evaluation of an incomplete intestinal obstruction is to distinguish between infectious and malignant etiologies.We present a case of an elderly woman complaining of abdominal pain accompanied with nausea and vomiting,and failure to pass gas or stools.Anti-tuberculosis drugs were used to relieve her abdominal pain,and a needle biopsy of the peritoneal cavity showed evidence of primary papillary serous carcinoma of the peritoneum(PSCP). This is a rare description of tuberculosis in the setting of PSCP.This report illustrates the potential complex nature of malignancies,and emphasizes the need to consider coexistence of malignancy and infection in patients, especially in those with risk factors for malignancy who fail with antibiotic therapy.

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.

A Case of Serous Tubal Intraepithelial Carcinoma Diagnosed by Cytology during the Operation

We experienced a case of serous tubal intraepithelial carcinoma (STIC), which is the earliest morphologically recognizable precursor of pelvic high grade serous carcinoma, diagnosed by cytology during the operation. A 48-year-old Japanese woman visited to our department because of abnormal cytological result and the left adnexal mass on female cancer screening. Pre-operatively, she was diagnosed as cervical intraepithelial neoplasia (CIN) 3, adenomyosis, and the left adnexal cystic lesion with papillary growth. At laparotomy, the left adnexal tumor turned out to be cystic fallopian tube with small papillary growth on the inner surface, but abnormal findings were not present on bilateral ovaries. The cytology of the imprint smears from the papillary projection and ascitic fluid showed positive, suggesting serous adenocarcinoma. Histopathological examination of the lesion revealed the left fallopian tube lesion was STIC with immunohistochemically positive reactivity against p53. No metastases including disseminated lesions were noted. The patient received four courses of systemic chemotherapy, and had no recurrent signs 10 months after the operation.

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。

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.

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。

子宫浆液性癌20例分子学特征及临床分析

目的:总结子宫浆液性癌(uterine serous carcinoma,USC)的临床病理特征,探讨其分子分型及人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)的表达。方法:收集20例USC患者的临床资料,采用HE、免疫组织化学、Sanger测序和荧光原位杂交(fluorescence in situ hybridization,FISH)方法对石蜡标本进行检测,进行分子分型并分析HER2的表达。结果:USC占同期子宫内膜癌的8%,国际妇产科联盟(International Federation of Gynecology and Obstetrics,FIGO)Ⅰ期5例(25%)、Ⅱ期1例(5%)、Ⅲ期9例(45%)、Ⅳ期5例(25%)。癌组织可见乳头、腺腔、实性3种组织学结构;乳头宽大或细小,细胞易脱落,边缘不光滑;腺腔多呈裂隙样。细胞异型较大,可见奇异核,胞质透亮或嗜酸,核分裂象易见,13例(65%)可见脉管内癌栓。雌激素受体、孕激素受体、波形蛋白、WT1和P16阳性率分别为40%、25%、10%、35%、100%,Ki-67阳性率30%~80%。20例USC均未检测到DNA聚合酶ε(DNA polymerase epsilon,POLE)突变,MLH1、PMS2、MSH2、MSH6均阳性,16例(75%)P53错义突变,4例(25%)无义突变。HER2免疫组织化学染色3+者5例(25%),其中4例经FISH检测见扩增信号。结论:USC发病率较低,病理形态多样,免疫组织化学染色有助于其鉴别诊断。USC分子分型均为P53突变型,HER2有望成为USC治疗的潜在靶点。

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。