国产人附睾分泌蛋白4（HE4）ELISA试剂盒与CA_（125）联合诊断上皮性卵巢癌的研究

目的评价人附睾分泌蛋白4（HE4）ELISA试剂盒与CA125联合诊断卵巢癌的意义;方法两种（HE4）ELISA法检测上皮性卵巢癌114例。对照组为盆腔包块疑似样本59例,其他妇科良性疾病30例,肺癌、结直肠癌及乳腺癌患者45例,孕妇血清30例,正常人血清100例。实验组检测CA125。结果 HE4_义翘和HE4_康乃格试剂盒诊断卵巢癌敏感性为74.6%和70.2%,联合CA125诊断敏感性为73.2%和68.8%;在早期和晚期卵巢癌的诊断中,HE4_义翘试剂盒敏感性为66.7%和79%,HE4_康乃格试剂盒敏感性为48.1%和79%;HE4_义翘联合CA125敏感性为66.7%和77.2%,HE4_康乃格联合CA125敏感性为48%和77.2%。两试剂盒在各组数据中有强的相关性,相关系数为0.963。结论 HE4_义翘试剂盒在早期诊断卵巢癌方面较好。     

血清HE4及CA125对子宫内膜癌宫外转移的预测价值

目的:评估术前血清HE4和CA125联合检测在子宫内膜癌(EC)的子宫外转移的诊断价值。方法:回顾分析327例EC患者的临床病理资料,检测血清HE4和CA125水平,分析HE4及CA125与临床病理参数的关系,计算诊断评价指标,绘制受试者工作特征(ROC)曲线,计算AUC值。结果:患者血清HE4和CA125水平与病灶范围大小、肌层浸润深度、肿瘤分化程度、临床分期、有无子宫外转移等有关,差异有统计学意义(P0.01)。血清HE4、CA125单项检测子宫外转移时,HE4敏感度最高,为57.81%,联合诊断能显著提高敏感度达79.68%。两项单独检测的ROC-AUC值分别为0.740、0.714,而联合诊断的ROC-AUC值为0.810,差异有统计学意义(P0.001)。结论:血清HE4和CA125联合预测EC患者的子宫外转移比单项检测更具优势。     

人附睾分泌蛋白4、糖链多肽抗原125联合卵巢恶性肿瘤风险预测模型对上皮性卵巢癌预测和诊断价值

目的 探讨血清中肿瘤标志物人附睾分泌蛋白4（HE4）、糖链多肽抗原125（CA125）和卵巢恶性肿瘤风险预测模型(ROMA)预测和诊断上皮性卵巢癌的临床价值。方法 回顾性分析于2012年1月至2014年4月天津市中心妇产科医院因盆腔肿物就诊的225例病人,其中卵巢上皮癌113例,卵巢良性肿瘤112例,因体检来院的健康妇女33例。采用电化学发光法测定受试者术前血清HE4和CA125浓度,用卵巢风险评估模型计算ROMA指数。结果 卵巢癌组CA125、HE4及ROMA值高于卵巢良性肿瘤组和健康对照组,差异均有统计学意义（P＜0.05）。卵巢良性肿瘤组CA125、HE4及ROMA值与健康对照组比较,差异无统计学意义（P＞0.05）。HE4、CA125、ROMA值诊断卵巢恶性肿瘤的敏感度分别为52.21%、85.84%、86.73%,特异度分别为100%、88.39%、83.93%,三者相比较,ROMA值的敏感度最好,HE4特异度最好。ROMA值绝经前后敏感度分别为85.71%和69.77%,特异度分别为86.90%和75%。结论 HE4作为一种新型肿瘤标志物,其在卵巢上皮性癌中具有重要的诊断价值,而ROMA值预测患卵巢癌风险的敏感度较CA125、HE4二者单项高,有助于帮助临床医生评估患卵巢上皮性癌的风险性。     

HE4—一种新的卵巢上皮性癌肿瘤标记物的研究进展

CA125是目前临床上广泛用于诊断卵巢上皮性癌的肿瘤标记物,然而其诊断卵巢上皮性癌的敏感性及特异性并不十分满意,因此,卵巢上皮性癌肿瘤标记物的研究成为近年妇瘤领域的一个热点。自从卵巢癌相关基因人附睾蛋白4(HE4)发现以来,国内外对HE4进行了一些相关研究,认为HE4有可能成为一个良好的卵巢上皮性癌的肿瘤标记物。现对HE4的结构、表达及其在卵巢上皮性癌的诊断、疗效评估等方面的进展做一综述。     

联合检测人附睾蛋白4与血清CA125用于诊断卵巢上皮性癌的诊断价值

目的:研究人附睾蛋白4(HE4)在卵巢上皮性癌患者血清及尿液中的表达水平,探讨其联合血清CA125用于卵巢上皮性癌诊断的临床应用价值。方法:采用酶联免疫吸附法(ELISA法)检测50例卵巢上皮性癌患者、38例卵巢良性肿瘤患者和40例正常人血清及尿液中的HE4水平和血清CA125水平。结果:卵巢癌患者组血清及尿液中的HE4水平明显高于卵巢良性肿瘤组及正常对照组,差异均有统计学意义(P<0.05),血清及尿液HE4水平在卵巢良性肿瘤组及正常对照组之间差异无统计学意义(P>0.05)。血清HE4检测卵巢上皮性癌的灵敏度、特异度分别为58.0%、87.2%,与血清CA125联合检测其灵敏度、特异度提高至86.0%、89.7%;尿液HE4检测卵巢上皮性癌的灵敏度、特异度分别80.0%、91.0%,与血清CA125联合检测其灵敏度、特异度可达90.0%、94.9%;联合检测血清HE4、尿液HE4和血清CA125的灵敏度和特异度高达94.0%、94.9%。结论:联合检测血清及尿液HE4与血清CA125可显著提高卵巢上皮性癌的诊断率。     

癌抗原125、附睾特异性蛋白-4在评估卵巢上皮性癌化疗效果中的价值

目前,卵巢癌全球新发病例大约在16.5万人次/年。如果肿瘤能在早期被诊断,或者在治疗后复发的早期被诊断,都将对于患者的预后有着很大的益处。然而,在多年的临床与实验室研究中,针对卵巢癌的特异性标志物,目前在国际上被广泛使用的只有癌抗原125(CA125)。在最近的10年中,虽然已经有多个肿瘤标志物在卵巢癌患者的血液中被发现,但是他们在预测疾病中的敏感性和特异性都远     

血清人附睾分泌蛋白4（HE_4）和CA_（125）在卵巢癌患者手术及化疗前后的变化

目的检测卵巢癌患者手术及化疗前后HE4和CA125的血清值,探讨卵巢癌患者治疗前后HE4、CA125的变化情况。方法采用酶联免疫吸附试验（ELISA法）检测21例卵巢癌患者治疗过程中血清HE4和CA125水平。数据使用SPSS13.0进行统计学分析。结果卵巢癌患者术后行常规化疗,血清HE4及CA125的水平基本下降到正常。术前HE4中位数水平为796.32pmol/L,第2次后基本恢复正常,为135.61pmol/L;患者术前CA125中位数水平为1280kU/L,第3次化疗后为30.4kU/L,恢复正常。卵巢癌患者治疗过程中HE4与CA125具有较强的相关性,相关系数为0.811。结论 HE4可能作为有助于评判疗效的另一种血清学标志物。     

上皮性卵巢肿瘤患者血清中YKL-40、HE4的表达及临床意义

目的:探讨血清甲壳质酶蛋白40(YKL-40)、人附睾蛋白4(HE4)在上皮性卵巢肿瘤的表达及临床意义。方法:用酶联免疫吸附试验,检测健康妇女、上皮性良性卵巢肿瘤、交界性卵巢肿瘤及卵巢癌患者血清中YKL-40、HE4的水平。结果:(1)健康妇女、上皮性良性卵巢肿瘤、交界性卵巢肿瘤及卵巢癌患者术前血清中,YKL-40表达中位数分别为35.56、41.42、44.34和130.25μg/L;HE4的表达中位数分别为41.10、43.98、65.21和260.90pmol/L;在术前卵巢癌组YKL-40、HE4的表达水平均高于前3组,差异有统计学意义(P<0.05),前3组之间差异无统计学意义;卵巢癌患者术后血清中YKL-40、HE4中位数分别为58.57μg/L、124.32pmol/L,术前血清水平明显高于术后(P<0.05);(2)卵巢癌患者术前血清YKL-40浓度与FIGO分期、血清CA125浓度呈正相关(P<0.05);术前血清HE4浓度与病理类型、血清CA125浓度、年龄相关。结论:血清YKL-40、HE4有望成为卵巢癌标志物,用于早期诊断和预后分析。     

人附睾蛋白4检测早期卵巢癌

卵巢癌是威胁女性生命健康的三大生殖道恶性肿瘤之一,其年轻化趋势明显且死亡率高居首位,如何提高卵巢癌患者早期检出率是降低该病死亡率的关键。传统卵巢癌标记物——糖类抗原125(CA125)虽然广泛应用于临床,但是敏感度和特异度较低,并且在一些妇科良性疾病中也出现非特异性的升高,因此迫切需要一种高敏感度和特异度的检测指标。近年来颇受瞩目的血清标记物——人附睾蛋白4(HE4)成为了早期诊断卵巢癌的焦点,相比于CA125,HE4在大多数非卵巢恶性肿瘤中不表达或低表达,并且单独检测HE4或联合CA125在对卵巢癌的早期诊断、疗效和预后评价等方面更具优势,现已在国外和国内多家三甲医院推广应用。现对HE4的发现、发展和临床应用及其与CA125构建的卵巢恶性肿瘤发病风险模型(ROMA)作综述。     

血清HE4水平对预测卵巢癌铂类化疗效果的临床观察

目的:探讨卵巢上皮癌患者血清中人附睾蛋白4(HE4)的水平与患者铂类化疗效果的关系。方法:回顾分析52例卵巢上皮癌患者的临床资料和随访信息,采用电化学发光法检测患者治疗前和随访时血清HE4及CA125水平,分析血清HE4及CA125水平与铂类化疗效果的关系。结果:52例患者中,31例铂类化疗敏感,21例铂类化疗抵抗。铂类化疗抵抗组患者治疗前血清HE4及CA125水平明显高于铂类化疗敏感组。治疗前血清HE4水平对卵巢癌铂类化疗疗效的预测效能高于CA125。铂类化疗抵抗组患者随访时血清HE4水平明显高于铂类化疗敏感组(276.5pmo/L vs 56.38pmo/L,P0.001)。随访时血清HE4可预测铂类化疗效果,当界值点为127.40pmo/L时,灵敏度达81%,特异度达93.5%,阳性预测值(PPV)为89.5%,阴性预测值(NPV)为87.9%,曲线下面积(AUC)为0.919。随访时血清CA125取界值点为76.4U/L时预测铂类化疗效果的灵敏度为95.2%,特异度为90.3%,PPV为85%,NPV为87.5%,AUC为0.876。随访时血清HE4预测铂类化疗效果的AUC也大于CA125。Logistic多因素回归分析结果显示,随访时血清HE4水平与发生铂类化疗抵抗密切相关(P=0.027)。结论:随访时血清HE4水平可以预测卵巢癌铂类化疗的反应。     

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.     

血清CA125水平测定在预测卵巢上皮性癌复发和预后中的价值

目的 分析卵巢上皮性癌(卵巢癌)患者在初次治疗的不同阶段血清CA125水平与卵巢癌复发和预后的关系.方法 收集2002年1月-2005年12月间浙江大学医学院附属妇产科医院经病理检查证实的151例原发性卵巢癌患者的临床病理资料并进行随访,分析初次治疗的不同阶段血清CA125水平与临床病理参数、2年复发率和5年复发率、5年生存率及无瘤生存期和总生存期的相关性.结果 卵巢癌患者术前血清CA125水平、化疗3个疗程结束时CA125是否降为正常与大多数预后相关的临床病理参数相关,包括分期、病理分级、腹水量、残留病灶大小、复发类型、2年复发率、5年复发率及5年生存率(P均＜0.05).术前及化疗3个疗程结束时血清CA125水平与无瘤生存期和总生存期呈显著性相关(P均＜0.01).但未见手术前后CA125下降幅度与复发和预后的相关性(P均＞0.05).结论 术前及化疗3个疗程结束时血清CA125水平可用于预测卵巢癌的复发和预后.     

上皮性卵巢癌PTEN蛋白表达分析

目的：探讨抑癌基因PTEN的蛋白表达与上皮性卵巢癌的发生、发展之间的关系。方法：对74例上皮性卵巢癌应用免疫组化方法检测PTEN蛋白的表达。结果：上皮性卵巢癌中PTEN蛋白有一定的表达缺失，在G1、G2级组织表达率（90．62％）高于G3级组织表达率（66．67％），二者差异有显著性；不同的临床分期中，I、Ⅱ期阳性表达为22／24（91．67％），Ⅲ、Ⅳ期阳性表达为35／50（70％），二者差异有显著性。在浆液性和粘液性两种不同的组织类型间，表达率分别为82．98％和66．67％，二者无明显差别。结论：PTEN蛋白的表达缺失在上皮性卵巢癌的发生、发展过程中有一定的作用，且与病变进展和分化有关。     

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。     

Gelatinase A-immunoreactive protein in ovarian lesions- prognostic value in epithelial ovarian cancer.

OBJECTIVE: Gelatinase A (MMP-2) is a member of the matrix metalloproteinase family and it degrades the major component of the basement membrane, type IV collagen. MMP-2 has been linked to invasion in different types of cancer. METHOD: We have studied the localization of MMP-2 in 18 benign, 3 borderline, and 33 malignant ovarian lesions by immunohistochemical stainings using a monoclonal antibody against MMP-2. RESULTS: MMP-2-immunoreactive protein was localized in epithelial cells and in fibroblasts. Two types of cytoplasmic staining were observed, a diffuse and a granular pattern. The diffuse staining model was found more often. In 19% of the cases, both staining patterns were present in epithelial cells. Granular staining was found in epithelial cells in cystadenomas and in ovarian cancer cells. The pattern of MMP-2 positivity in fibroblasts was diffuse. MMP-2 positivity in cancer cells was associated with recurrent disease (P < 0.05) in ovarian cancers. MMP-2 negativity in fibroblasts correlated to Grade 3 (P < 0.01), Stage III-IV (P < 0.001), recurrency (P < 0.05), and refractory disease (P < 0.05) in ovarian cancer. The relative survival rate was 32% in patients with an MMP-2-positive ovarian cancer, 57% in patients with an MMP-2-negative ovarian cancer, and 19% in patients with MMP-2 positivity in cancer cells and concomitant negativity in stromal fibroblasts. The disease-free 5-year survival rates were 25, 57, and 12.5%, respectively. CONCLUSIONS: These data suggest that MMP-2 may contribute to poor prognosis of ovarian cancer.     

卵巢上皮性癌复发的处理

目的 探讨影响卵巢上皮性癌复发的因素及处理方法。方法 对１８９例卵巢癌进行回顾性分析,全部手术切除标本均经病理检查证实。结果 １８９例中,复发３１例。其中１９例为我院施行肿瘤细胞减灭术,残留癌灶直径≤２ｃｍ;１２例为外院施行肿瘤细胞减灭术,达到临床愈后因复发转入我院。复发的３１例初次手术中,Ⅰ、Ⅱ期４例（１２．９％）,Ⅲ、Ⅳ期２７例（８７．１％）。其中１０例手术切净者,平均复发时间为１７．２个月;     

Significance of multi-drug-resistant proteins in predicting chemotherapy response and prognosis in epithelial ovarian cancer

OBJECTIVES: To clarify the expression of multi-drug-resistant (MDR) markers, GST-pi, c-Jun, P-glycoprotein (Pgp), and MDR-associated protein (MRP) in epithelial ovarian cancer, and to determine whether their expression is predictive of chemotherapy response and patient prognosis. METHODS: Specimens of 58 epithelial ovarian cancer cases obtained at initial surgery were studied immunohistochemically using antibodies. RESULTS: Overall positive rates in the 58 specimens were 58.6% for GST-pi, 44.8% for c-Jun, 27.6% for Pgp, and 22.4% for MRP. The 5-year disease-free survival rate was 26.0% for patients with MRP-positive tumors and 75.2% for those with MRP-negative tumors. The prognosis for those with MRP-positive tumors was significantly poorer (p < 0.05). Patients with GST-pi-positive tumors had a significantly worse prognosis than those with GST-pi-negative tumors (51.9% vs 79.2%, p < 0.05). Multivariate analysis showed that residual tumors 2 cm or larger and MRP expression were independent prognostic factors for chemotherapy resistance. The relative risk of chemotherapy resistance in a patient with a residual tumor 2 cm or larger, positive MRP, and positive GST-pi was 10.6 times greater than the risk in a patient without these factors. CONCLUSION: MRP and GST-pi expression might be potential predictors of the response to standard chemotherapy in epithelial ovarian cancer. Their expression also might contribute to individualizing clinical trials of postoperative chemotherapy.