卵巢癌中蛋白激酶C的表达及其临床意义

目的　探讨上皮性卵巢癌组织蛋白激酶C (proteinkinaseC ,PKC)的表达和化疗耐药的关系 ,以及与P -糖蛋白 (P -gp)的相关性。方法　用免疫组化S -P法检测 35例卵巢上皮性肿瘤组织、 2 0例卵巢良性肿瘤组织和 2 0例正常卵巢组织中PKC和P -gp的表达 ,并进行相关临床因素分析。结果　①PKC、P -gp在卵巢恶性肿瘤中的表达明显高于在良性及正常组织中的表达 ;并且PKC和P -gp的表达有相关性 (P <0 0 5 ) ;②卵巢癌PKC的表达与临床病理因素无直接关系 ;③恶性肿瘤中 ,初治和复发的PKC表达阳性率分别为 34 8%和 75 % ;④化疗对PKC表达阳性和阴性卵巢癌患者的有效率分别为 2 3 5 %、 6 6 7% (P <0 0 5 ) ;⑤PKC表达阴性患者的预后优于阳性者 (P =0 0 39)。结论　PKC表达与卵巢癌组织化疗耐药明显相关 ,可能在P -gp介导的卵巢癌多药耐药中起重要作用。     

Methylation of the insulin-like growth factor binding protein-3 gene and prognosis of epithelial ovarian cancer

Insulin-like growth factor binding protein-3 (IGFBP-3) is a member of the IGFBP family, which regulates the mitogenic and antiapoptotic effects of insulin-like growth factors. Hypermethylation of the IGFBP-3 promoter has been found to suppress its expression. To evaluate the role of IGFBP-3 in ovarian cancer progression, we examined the survival of 235 consecutively selected epithelial ovarian cancer patients in association with IGFBP-3 promoter methylation and IGFBP-3 expression in tumor tissue. IGFBP-3 promoter methylation was analyzed using methylation-specific polymerase chain reaction. Cytosol protein was extracted and measured using a bicinchoninic acid assay; IGFBP-3 was measured by enzyme linked immunosorbent assay. Promoter methylation of the IGFBP-3 gene was detected in 44% (104/235) of patients. IGFBP-3 promoter methylation was associated with disease progression and death after adjusting for clinical and pathologic variables. The association was more evident in patients with early-stage disease: RR = 2.87 (95% CI: 0.78-10.63) for disease progression and RR = 3.94 (95% CI: 0.91-15.78) for death. Tissue levels of IGFBP-3 did not differ by methylation status but were inversely associated with disease stage and residual tumor size. These results suggest that IGFBP-3 promoter methylation may be a useful prognostic marker for disease progression and death in early-stage ovarian cancer.     

富含半胱氨酸的酸性分泌蛋白基因在卵巢上皮性癌中的甲基化状态及临床意义

目的探讨富含半胱氨酸的酸性分泌蛋白(secreted protein acidicand rich in cysteine,SPARC)基因在卵巢上皮性癌组织中的甲基化状态及临床意义。方法采用甲基化特异性聚合酶链反应(MSP)检测2008-2010年由兰州大学第一医院病理科提供的40例原发性卵巢上皮性癌、30例卵巢良性肿瘤及10例正常卵巢石蜡包埋组织中SPARC基因启动子区域甲基化的状态。结果 SPARC基因启动子区甲基化在原发性卵巢上皮性癌组织、卵巢良性肿瘤组织及正常卵巢组织中的发生率分别为65.0%(26/40)、26.7%(8/30)及20%(2/10),癌组织中SPARC甲基化率显著高于良性肿瘤组织及正常卵巢组织(P<0.05),而良性肿瘤组织与正常组织相比差异无统计学意义(P>0.05),浆液性癌与黏液性癌之间SPARC甲基化率差异无统计学意义(P>0.05)。低分化癌组中SPARC基因启动子区甲基化发生率高于高分化癌组(P<0.05),临床Ⅲ期和Ⅳ期SPARC基因启动子区甲基化发生率高于Ⅰ期和Ⅱ期(P<0.05),有腹水组与无腹水组相比差异有统计学意义(P<0.05),而有无淋巴结转移组间相比差异...     

Prognostic significance of human epididymis protein 4 in epithelial ovarian cancer

Objective

The purpose of this study was to evaluate the prognostic significance of serum human epididymis protein 4 (HE4) level in patients with epithelial ovarian cancer.

Study design

A total of 78 women diagnosed with a pelvic mass and operated on in our institute comprised our cohort. Forty-five of these were diagnosed with epithelial ovarian cancer and treated with debulking surgery, followed by taxane and platinum-based chemotherapy as clinically indicated. Preoperatively obtained serum samples were analyzed for levels of HE4 and CA125.

Results

The elevated serum HE4 level was related to advanced stage and serous type of cancer. The median duration of the follow-up was 35.1 months. In advanced stage, the median progression-free survival (PFS) of patients with elevated serum HE4 levels was 20.1 months (95% CI, 15.7–24.6 months), whereas that of patients with normal serum HE4 level was 24.2 months (95% CI, 13.9–34.6 months) (p = 0.029). Independent predictors for PFS in patients with advanced stage EOC included serum HE4 level (hazard ratio 2.24; 95% CI, 1.14 to 6.84; p = 0.048).

Conclusions

Our results demonstrated that an elevated serum HE4 level was related to the advanced stage of epithelial ovarian cancer. An elevated serum level of HE4 is a poor prognostic factor for PFS in patients with epithelial ovarian cancer who were treated with debulking surgery and adjuvant taxane and platinum-based chemotherapy. The serum HE4 level is a promising indicator for the progression of cancer as well as a biomarker for the detection of epithelial ovarian cancer.     

Prognostic role of immunosuppressive acidic protein in advanced ovarian cancer

OBJECTIVE: Our purpose was to investigate immunosuppressive acidic protein in the prognostic characterization of advanced ovarian cancer. STUDY DESIGN: Serum levels of immunosuppressive protein were prospectively measured in 80 patients with untreated ovarian carcinoma. To evaluate the prognostic significance of immunosuppressive acidic protein levels, cutoff points were studied every 50 μg/ml between 450 and 1350 μg/ml. RESULTS: Pretreatment immunosuppressive acidic protein levels were not significantly associated with stage, histotype, grade of differentiation, postoperative residual tumor, and response to chemotherapy. The most significant association with survival was observed at a cutoff value of 1100 μg/ml (p = 0.0089). In the univariate analysis for overall survival, International Federation of Gynecology and Obstetrics stage and immunosuppressive acidic protein status were found to have a role in predicting ovarian cancer prognosis. In the multivariate analysis only immunosuppressive acidic protein status was significantly associated with survival. A statistical correlation was found between serum levels and overall survival (p = 0.0104, χ² 6.56), including immunosuppressive acidic protein as a continuous variable. CONCLUSION: Our data suggest that immunosuppressive acidic protein assay is a potentially useful tool in the prognostic characterization of advanced ovarian cancer. (Am J Obstet Gynecol 1996;175:1606-10.)     

粘着斑激酶在卵巢上皮性癌中的表达及意义

目的 研究粘着斑激酶（FAK）在上皮性卵巢癌中的表达情况，探讨FAK与卵巢癌的关系及其临床生物学意义。方法 采用免疫组化方法测定卵巢癌组织FAK的表达情况，分别用人工半定量分析和计算机图像分析判定结果，并与各项临床指标进行统计学分析。结果 人工半定量分析与计算机图像分析结果高度正相关。FAK在正常卵巢、良性、交界性及恶性卵巢上皮性肿瘤中的表达水平依次增高（P〈0．05），高表达率分别为0、6.7％、40％、81．9％。手术病理期别高、远处转移、淋巴结转移、有腹水的患者癌组织FAK表达量高（P〈0．05）；癌组织FAK高表达与生存期短相关（P=0．063〈0．1）。结论 FAK可能与上皮性卵巢癌的发生侵袭、转移及不良预后相关。     

TFAR19蛋白在卵巢上皮性癌中的表达

目的探讨TFAR19蛋白在卵巢上皮性癌组织中的表达情况及关系。方法应用免疫组化方法检测TFAR19蛋白在79例卵巢上皮性癌组织(其中浆液性腺癌33例,粘液性腺癌13例,子宫内膜样腺癌11例,其他类型卵巢上皮性癌22例),33例卵巢良性肿瘤组织(其中浆液性腺瘤18例,粘液性腺瘤13例,其他良性肿瘤2例)及11例正常卵巢组织中的表达。结果39.24％的卵巢上皮性癌、81.82％的正常卵巢上皮、75.76％的卵巢良性肿瘤组织中TFAR19蛋白呈强阳性表达,卵巢上皮性癌与卵巢良性肿瘤组织及正常卵巢上皮相比差异有显著性(P<0.05)。不同FIGO分期(1986年)卵巢上皮性癌中强阳性表达比例分别为FIGO I期:80％,FICOⅡ期45.45％,FIGOⅢ期31.25％,FIGOⅣ期30％;不同组织学分级卵巢上皮性癌中TFAR19的强阳性表达分别为G1期62.5％,G2期50％,G3期29.79％;卵巢粘液性癌组织中TFAR19蛋白的强阳性表达明显高于浆液性腺癌与子宫内膜样癌。结论TFAR19蛋白的表达与卵巢上皮性癌的FIGO分期、组织学分级、病理类型相关。随FIGO分期与组织学分级升高,TFAR19蛋自的表达下调。TFAR19蛋白可能是卵巢上皮性癌细胞细胞凋亡的重要调控因子。     

血清人附睾蛋白4在卵巢癌临床转归中的关系

目的围手术期及化疗期间人附睾蛋白4（HE4）血清水平的变化,与卵巢癌的疗效和无瘤进展生存时间（PFS）的关系尚不清楚,本文通过检测卵巢上皮性癌不同时期的HE4水平,探讨其与卵巢癌临床转归的关系。方法 取2005年11月至2009年12月间北京大学人民医院诊治并随访完整的卵巢上皮性癌患者（n=100）的血清样本,采用酶联免疫吸附试验法,测定患者不同时期的血清HE4水平。中位随访时间为17个月（3~55个月）。结果本研究共检测了100例患者共559份血清的HE4水平。在有连续性资料的73例患者中,初治疗效为完全缓解组与未完全缓解组相比,化疗期间HE4下降更迅速,差异有统计学意义。单因素分析主要显示了首次化疗前HE4水平与PFS明显相关：首次化疗前HE4水平≤150 pmol/L组的中位PFS较HE4〉150pmol/L组延长（34 vs 17.5个月,P=0.001）。多因素分析显示,首次化疗前HE4水平未降至正常是晚期卵巢癌患者PFS的独立危险因素。首次化疗前HE4水平与残余瘤灶大小呈中度相关（r=0.458,P〈0.001）。结论手术前后及化疗期间HE4变化情况有助于判断初治效果;首次化疗前HE4水平一定程度上反映了手术的满意程度,是晚期卵巢癌的PFS的相对独立影响因素。     

Taxol given weekly in advanced previously treated ovarian carcinomas – a pilot study

In this pilot study, 42 patients with advanced ovarian carcinoma were treated with Taxol weekly instead of every 3 weeks. The initial dose was 67 mg m⁻². The clinical response rate was 29%. The response rate was 22% for patients with platinum-resistant tumors compared to 42% for patients with platinum-sensitive tumors. This difference was not statistically significant. The median progression free survival was 110 days and the median overall survival 341 days. The toxicity was acceptable and probably less pronounced than with the standard tri-weekly schedule. A randomized multicenter study comparing these two treatment schedules is presently under way in Scandinavia.     

BRCA1 expression in a large series of sporadic ovarian carcinomas: a Gynecologic Oncology Group study

Abstract.   Thrall M, Gallion HH, Kryscio R, Kapali M, Armstrong DK, Deloia JA. BRCA1 expression in a large series of sporadic ovarian carcinomas: a Gynecologic Oncology Group study. Int J Gynecol Cancer 2006; 16(Suppl. 1): 166–171.
BRCA1 is a tumor suppressor gene that, when mutated, is associated with the development of hereditary ovarian cancer. A role for BRCA1 in the pathoetiology of sporadic ovarian epithelial cancer (OEC) development has been suggested, although spontaneous mutations of the BRCA1 gene in this disease are uncommon. Loss of gene function by epigenetic alteration is observed more commonly, while other means of gene inactivation have not been intensively investigated. We examined expression and localization of the BRCA1 gene product by immunohistochemistry and sought to clarify the relationship between protein expression and tumor stage, grade, histopathologic subtype, and outcome. Among 230 spontaneous OEC tumors, we found a statistically significant decrease in BRCA1 protein expression with advancing stages of OEC. There was no relationship between expression and tumor grade. There was a statistically significant relationship between the pathologic subtypes of OEC and BRCA1 expression. Minimal BRCA1 expression was protective for survival. These findings confirm a high rate of loss of BRCA1 protein expression in sporadic OEC and suggest a role of BRCA1 in the progression of sporadic ovarian carcinoma.     

Mismatch repair protein deficiency in endometriosis: Precursor of endometriosis-associated ovarian cancer in women with lynch syndrome

ObjectiveWe aimed to elucidate the pathogenesis of ovarian cancer through the loss of mismatch repair (MMR) proteins in women with Lynch syndrome (LS) in this report.Case reportTwo women with LS underwent surgery for synchronous endometrial cancer and ovarian cancer. In both cases, immunohistochemical examination showed concomitant MMR protein deficiency in endometrial cancer, ovarian cancer, and contiguous ovarian endometriosis. In Case 1, the macroscopically normal ovary included multiple endometrioses with MSH2 and MSH6 expression, and FIGO grade 1 endometrioid carcinoma and contiguous endometriosis without MSH2 and MSH6 expression. In Case 2, all endometriotic cells contiguous with carcinoma in the lumen of the ovarian cyst showed loss of the expression of MSH2 and MSH6.ConclusionOvarian endometriosis with MMR protein deficiency may progress to endometriosis-associated ovarian cancer in women with LS. Diagnosing endometriosis in women with LS during surveillance is important.     

Serum MAGE-4 protein in ovarian cancer patients

OBJECTIVE: We measured serum levels of MAGE-4 protein in patients with ovarian cancer to investigate the relationship between serum MAGE-4 positivity and prognosis. METHODS: Serum levels of MAGE-4 protein were measured with an ELISA system. RESULTS: Serum levels of MAGE-4 in patients with ovarian cancer were significantly higher than levels in patients with benign diseases. Serum MAGE-4 protein was considered positive in 22% of primary ovarian cancer patients. The positive rate was the highest in sera of patients with surface epithelial-stromal tumors, particularly serous adenocarcinomas (24%). The survival time after a primary surgical operation in ovarian cancer patients with serum MAGE-4 positivity was significantly shorter than that of MAGE-4-negative cases. CONCLUSION: These results suggest that serum MAGE-4 protein is a potential prognostic factor of reduced survival in ovarian cancer patients.