Reference ranges for HE4 and CA125 in a large Asian population by automated assays and diagnostic performances for ovarian cancer

Human epididymis protein 4 (HE4) is a new biomarker for the detection of ovarian cancer. We evaluated the analytical performance of a novel automated HE4 assay and established reference ranges of HE4 and CA125. We also compared the diagnostic performance of both biomarkers for ovarian cancer. Precision performances and linearity of the HE4 assay were assessed. Serum samples from 2,182 healthy and 72 pregnant women were also assayed for HE4 and CA125, and the 95%, 97.5% and 99% reference limits for both markers were calculated. Additionally, sera from 66 ovarian cancer and 257 benign gynecologic disease patients were tested to validate reference ranges and diagnostic performances. The total precision of the HE4 assay was <5% coefficient of variation for most of the levels evaluated. The linearity range of this assay was from 15.0 to 1100.0 pmol/L. The 97.5% upper reference limits for HE4 and CA125 were 33.2 pmol/L (95% confidence interval [CI], 32.2-34.0) and 38.3 U/mL (95% CI, 35.1-41.5), respectively. Using these values as cutoff points, the sensitivity and specificity of HE4 for differentiating ovarian cancer from benign gynecologic diseases and healthy individuals were 90.9% and 94.1%, and those of CA125 were 72.7% and 94.4%. The receiver operating characteristic-area under the curve values of HE4 and CA125 for discriminating ovarian cancer from age-matched control were 0.94 and 0.86, respectively, and they were statistically different (p = 0.0095). The new automated HE4 assay showed good analytical and diagnostic performances. The reference limits established in our study could be used as cutoff levels to facilitate more accurate diagnosis of ovarian cancer in Asian population.     

血清人附睾分泌蛋白4(HE4)和CA125在卵巢癌患者围手术期的变化及临床意义

目的:监测卵巢癌手术前后血清人附睾分泌蛋白4 (human epididymis secretory protein 4,HE4)、CA125(即糖类抗原125)的变化,分析HE4和CA125在卵巢癌诊治中的价值.方法:选取180例卵巢癌患者,根据临床分期分为早期组90例和中晚期组90例,选取90例卵巢良性疾病者作为良性组、90例健康成年女性作为对照组,在手术前后分别监测各组血清HE4和CA125表达水平,统计分析不同检测方法的诊断价值,同时随访卵巢癌患者12个月,对卵巢癌复发患者与未复发患者在手术前后的血清HE4和CA125进行统计分析.结果:血清HE4联合CA125特异度(98.89％)、阳性预测价值(99.27％)显著高于HE4单独检测及CA125单独检测,P＜0.05,组间有统计差异;手术后,卵巢癌患者血清HE4、CA125显著下降(P＜0.05),但是,在相同监测点,卵巢癌者血清HE4和CA125显著高于对照组和良性组(P＜0.05),且中晚期组血清HE4显著高于早期组(P＜0.05),良性组血清HE4、CA125略高于对照组,组间无显著差异(P＞0.05);卵巢癌复发者血清HE4、CA125显著高于未复发组者,P＜0.05,有统计学差异.结论:卵巢癌患者血清CA125和HE4显著异常升高,联合检测血清HE4和CA125不仅对于提高卵巢癌诊断特异性、阳性准确率具有重要价值,而且能够为预后评估提供可靠信息.     

HE4 联合 CA125 在卵巢癌早期诊断中的应用价值

目的：探讨人附睾蛋白4（HE4）联合癌抗原125（CA125）在卵巢癌早期诊断中的应用价值.方法：应用电化学发光法及酶联免疫法,测定20例卵巢癌患者、20例良性肿瘤患者（子宫肌瘤和卵巢肿瘤）及30例健康妇女血清CA125、HE4水平,比较各组血清CA125、HE4水平,分析两标记物联合在卵巢癌患者检测中的意义.结果：卵巢癌组CA125、HE4水平明显高于健康组及良性肿瘤组,差异有统计学意义（P＜0.05）,晚期卵巢癌组CA125、HE4水平明显高于早期卵巢癌组,差异有统计学意义（P＜0.05）.联合检测HE4及CA125敏感性高于二者中任一标志物,特异性与CA125检测一致,低于HE4检测.结论：HE4联合CA125测定有助于卵巢癌的诊断,可作为很好的卵巢癌标志物,提高早期卵巢癌的诊断率.     

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.     

血清中人附睾蛋白4、抑制素A及癌胚抗原125联合检测在卵巢癌诊断中的意义

目的：探讨人附睾蛋白4（HE4）、抑制素A（inhibinA）及癌胚抗原125（CA125）在卵巢癌患者中的诊断价值。方法：应用ELISA法检测卵巢癌组、卵巢良性肿瘤组及正常对照组患者血清中HE4、InhibinA、CA125水平。结果：血清HE4水平：卵巢癌组（133.86±127.94）pmol/L、卵巢良性肿瘤组（42.67±22.77）pmol/L、正常对照组（33.40±19.50）pmol/L;血清InhibinA水平：卵巢癌组（177.22±114.35）ng/L、卵巢良性肿瘤组（76.60±14.10）ng/L、正常对照组（70.70±21.66）ng/L;血清CA125水平：卵巢癌组（750.52±1230.34）U/L、卵巢良性肿瘤组（67.25±106.16）U/L、正常对照组（17.69±6.13）U/L。统计学分析血清HE4、InhibinA数值显示：卵巢癌组与卵巢良性肿瘤组、正常对照组比较,P〈0.05,差异有统计学意义;而卵巢良性肿瘤组与正常对照组比较,P〉0.05,差异无统计学意义。血清CA125卵巢癌组与卵巢良性肿瘤组、正常对照组比较,P〈0.05,差异有统计学意义;良性肿瘤组与正常对照组比较,P〈0.05,差异有统计学意义。卵巢癌诊断中的阳性率分别是：HE4 71.8%、InhibinA 66.7%、CA125 61.5%,三者联合阳性率为92.3%。结论：HE4、InhibinA、CA125在卵巢癌诊断中有重要意义,三者联合检测能明显提高卵巢癌的诊断率。     

人附睾蛋白4与糖类抗原125联合检测在卵巢癌诊断中的应用价值

目的 探讨患者血清人附睾蛋白4(HE4)与糖类抗原125(CA125)联合检测及卵巢恶性风险计算法(ROMA)在卵巢癌诊断中的价值.方法 采用酶联免疫吸附试验(ELISA)检测119例卵巢癌患者(卵巢癌组)、36例交界性卵巢肿瘤(交界性组)、96例卵巢良性肿瘤患者(良性组)及53例女性健康对照者(健康对照组)的血清HE4浓度,同时用电化学发光法检测患者的血清CA125浓度,综合评价HE4与CA125组合的检测效能.结合女性的月经状态,采用ROMA方法计算卵巢癌预测概率(PP),评价PP值的诊断效果.结果 根据受试者工作特性曲线(ROC)分析,HE4的临界值为67.3 pmol/L,灵敏度和特异度分别为80.7%和94.6%.治疗前卵巢癌组患者血清HE4和CA125的中位浓度分别为227.3 pmol/L和444.0 U/ml,与交界性组、良性组和健康对照组差异均有统计学意义(均P＜0.01).手术治疗后,卵巢癌患者的血清HE4和CA125水平明显降低(均P＜0.01).HE4与CA125联合检测时,灵敏度和特异度分别为92.7%和72.5%.未绝经和绝经女性PP值的临界值分别为9.3%和27.3%,诊断未绝经患者的灵敏度和特异度分别为84.6%和77.0%,阳性预测值和阴性预测值分别为70.2%和88.7%;诊断绝经患者的灵敏度和特异度分别为86.3%和77.1%,阳性预测值和阴性预测值分别为94.5%和71.1%.结论 血清HE4是一种良好的血清肿瘤标记物.HE4与CA125联合检测并借助ROMA判定卵巢癌的患病风险有助于提高卵巢癌诊断的准确度.

Abstract：

Objective To investigate the clinical value of combination of human epididymis protein 4 (HE4), CA125 and the Risk of Ovarian Malignancy Algorithm (ROMA) in diagnosis of ovarian carcinoma. Methods To detect the serum concentration of HE4 using ELISA and CA125 using ECL in patients of ovarian carcinoma group (n=119), borderline ovarian tumor group (n=36), benign ovarian neoplasm group (n=96) and female healthy control group (n=53). The ROMA based on the serum level of CA125, HE4 and a woman′s menopausal status was used to calculate the predicted probability (PP) and diagnostic results of ovarian cancers. Results The receiver operating characteristic (ROC) analysis showed the cut-off value was 67.3 pmol/L (the AUC was 0.906, the sensitivity was 80.7% and specificity was 94.6%). The serum levels of HE4 and CA125 in the ovarian carcinoma group were significantly higher than that in the borderline ovarian tumor group, benign ovarian neoplasm group and female healthy control group (P<0.01). The serum levels of CA125 and HE4 showed statistically no significant difference between the borderline ovarian tumor group and benign ovarian neoplasm group (P>0.05). The levels of HE4 and CA125 were reduced significantly in ovarian patients after surgery therapy (P＜0.01). The sensitivity and specificity of HE4 + CA125 combination was 92.7% and 72.5%. The ROMA that can classify patients into high and low risk groups was established as 9.3% in premenopausal and 27.3% in postmenopausal women. Conclusions HE4 is a helpful biomarker for ovarian carcinoma diagnosis. Biomarker combination of HE4 and CA125, and applying of the ROMA are helpful to improve the accuracy in diagnosis of ovarian cancers.     

卵巢癌血清HE4、CA72-4、CA125水平测定

目的 探讨卵巢癌血清人附睾分泌蛋白4（HE4）、CA72-4、CA125水平及临床意义.方法 入组我院收治的卵巢癌患者45例、卵巢良性病变30例,并纳入同期女性健康体检者30例作为对照,采用电化学发光法分别检测各组血清中HE4、CA72-4、CA125水平.结果 卵巢癌组血清HE4、CA72-4、CA125水平均高于卵巢良性病变组和健康对照组（P〈0.05）.HE4以〉150 pmol·L-1,CA72-4以5.3 u·mL-1,CA125以35 u·mL-1为阳性参考值,三者联合检测的敏感性为93.3%,特异性为73.3%.结论 卵巢癌患者血清中HE4、CA72-4、CA125处于高水平,联合检测可提高卵巢癌的诊断率.     

Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts

Human epididymal secretory protein E4 (HE4, also known as WAP four-disulphide core domain protein 2) is a new promising biomarker for ovarian cancer but its specificity against ovarian endometriotic cysts is only superficially known. We, thus, analysed serum HE4 concentrations together with a tumour marker CA125 in serum samples of women diagnosed with various types of endometriosis, endometrial cancer or ovarian cancer, and in samples from healthy controls. The mean serum concentration of HE4 was significantly higher in serum samples of patients with both endometrial (99.2 pM, P<0.001) and ovarian (1125.4 pM, P<0.001) cancer but not with ovarian endometriomas (46.0 pM) or other types of endometriosis (45.5 pM) as compared with healthy controls (40.5 pM). The serum CA125 concentrations were elevated in patients with ovarian cancer, advanced endometriosis with peritoneal or deep lesions, or ovarian endometriomas, but not in the patients with endometrial cancer. The microarray results revealed that the mRNA expression of the genes encoding HE4 and CA125 reflected the serum protein concentrations. Taken together, measuring both HE4 and CA125 serum concentrations increases the accuracy of ovarian cancer diagnosis and provides valuable information to discriminate ovarian tumours from ovarian endometriotic cysts.     

血清HE4及CA125水平检测在早期卵巢恶性肿瘤诊断中的价值

目的探讨血清人附睾蛋白4（HE4）及癌抗原125（CA125）水平检测在早期卵巢恶性肿瘤诊断中的价值。方法用酶联免疫吸附试验方法（ELISA）测定150例女性血清HE4、CA125水平,其中卵巢恶性肿瘤组（45例）、卵巢良性病变组55例及健康女性50例,分析两指标单独或联合检测诊断卵巢恶性肿瘤的价值。结果①卵巢恶性肿瘤组血清HE4和CA125水平（分别为344.66±256.37 pmol/L和516.07±609.07 U/ml）,分别与卵巢良性病变组（分别为53.77±19.03 pmol/L和41.17±62.08 U/ml）和正常组（分别为39.06±16.17 pmol/L和10.36±7.28 U/ml）比较,差异均有显著性（P〈0.001）;②根据ROC曲线,当HE4在80 pmol/L时诊断指数最大（0.806）,灵敏性和特异性分别为84.4%和92.4%,ROC曲线下面积0.948（95%CI 0.900～0.997,P=0.000）;③卵巢良性病变组血清HE4单项检测的假阳性率（5.5%）明显低于血清CA125单项检测的假阳性率（21.8%,P=0.012）;④HE4对早期卵巢癌的检测阳性率（73.3%）高于CA125检测的阳性率（33.3%,P=0.031）;⑤HE4单项检测对卵巢癌预测的特异度、阳性预测值（分别为94.6%和93.2%）高于CA125单项检测的特异度、阳性预测值（分别为78.2%和72.7%,P〈0.05）。联合CA125和HE4作为卵巢癌的诊断指标时,其诊断灵敏度为88.9%,高于单项血清CA125检测灵敏度（P〈0.05）。结论 HE4可作为卵巢癌诊断的独立生物学指标,其对早期卵巢癌的诊断价值优于CA125,两者联合检测可以提高CA125对卵巢癌的诊断能力。血清HE4水平以80 pmol/L为界值点对卵巢恶性肿瘤的诊断指数最大。     

HE4在浆液性卵巢癌组织中的表达及与临床病理因素的关系

目的：探讨人附睾分泌蛋白4（ HE4）在浆液性卵巢癌组织中的表达及与临床病理因素之间的关系。方法应用免疫组化的方法检测HE4在140例浆液性卵巢癌组织中的表达情况及与临床病理因素的关系,并联合检测CA125在卵巢癌中的组织学表达情况,对比HE4与CA125的相关性。结果HE4和CA125在中低分化浆液性卵巢癌组织中的阳性表达率分别为89．76％和81．89％,在高分化者阳性率分别为46．61％和15．38％,中晚期卵巢癌者阳性率为92．44％和83．19％,早期卵巢癌者阳性率为47．62％和33．33％,有盆腔淋巴结转移者阳性率95．65％和84．35％,无盆腔淋巴结转移者40．00％和36．00％,有腹腔种植者阳性率90．00％和87．27％,无腹腔种植者70．00％和33．33％,卵巢癌合并腹水者阳性率89．76％和79．53％,无腹水者为46．15％和38．46％,另外,HE4和CA125在浆液性卵巢癌中的阳性表达率分别为86％和76％,差异均具有统计学意义（ P＜0．05）,两者在卵巢癌的阳性表达上存在相关性（P＜0．05）。 HE4和CA125的表达与卵巢癌患者是否绝经和产数无关,（P＞0．05）。结论 HE4在浆液性卵巢癌组织中的表达与FIGO分期、肿瘤分化程度、淋巴结有无转移、腹腔有无种植和是否合并腹水有关。     

人附睾分泌蛋白4检测对子宫内膜癌的诊断及预后的意义

目的 比较血清人附睾分泌蛋白4(HE4)与CA125检测对早期及不同病理亚型子宫内膜癌的诊断价值.方法分别采用酶联免疫吸附试验及化学发光法对子宫内膜癌组(62例)及正常子宫内膜组(66例)血清HE4及CA125水平进行检测,评估两种诊断方法对子宫内膜癌的诊断价值.结果 (1)与正常组比较,HE4在子宫内膜癌患者血清中...     

HE4 and CA125 as a diagnostic test in ovarian cancer: prospective validation of the Risk of Ovarian Malignancy Algorithm

Background:

Recently, a Risk of Ovarian Malignancy Algorithm (ROMA) utilising human epididymis secretory protein 4 (HE4) and CA125 successfully classified patients as presenting a high or low risk for epithelial ovarian cancer (EOC). We validated this algorithm in an independent prospective study.

Methods:

Women with a pelvic mass, who were scheduled to have surgery, were enrolled in a prospective study. Preoperative serum levels of HE4 and CA125 were measured in 389 patients. The performance of each of the markers, as well as that of ROMA, was analysed.

Results:

When all malignant tumours were included, ROMA (receiver operator characteristic (ROC)-area under curve (AUC)=0.898) and HE4 (ROC-AUC)=0.857) did not perform significantly better than CA125 alone (ROC–AUC=0.877). Using a cutoff for ROMA of 12.5% for pre-menopausal patients, the test had a sensitivity of 67.5% and a specificity of 87.9%. With a cutoff of 14.4% for post-menopausal patients, the test had a sensitivity of 90.8% and a specificity of 66.3%. For EOC vs benign disease, the ROC–AUC of ROMA increased to 0.913 and for invasive EOC vs benign disease to 0.957.

Conclusion:

This independent validation study demonstrated similar performance indices to those recently published. However, in this study, HE4 and ROMA did not increase the detection of malignant disease compared with CA125 alone. Although the initial reports were promising, measurement of HE4 serum levels does not contribute to the diagnosis of ovarian cancer.     

联合检测HE4与OPN及CA125对卵巢癌诊断价值的探讨

目的:探讨血清人附睾分泌蛋白4(HE4)、骨桥蛋白(OPN)和CA125水平联合检测对卵巢恶性肿瘤的诊断价值.方法:在30例卵巢癌患者(卵巢癌组)、30例卵巢良性肿瘤患者(卵巢良性肿瘤组)和30例患子宫肌瘤等妇科疾病但卵巢正常者(对照组)中,采用酶联免疫吸附试验(ELISA)法检测HE4、OPN,全自动化学发光分析系统检测血清CA125.HE4参考范围0～80ρmol/L;OPN计算临界值为30 ng/mL,≥30 ng/mL为阳性;CA125≥35 U/mL为阳性.通过制作受试者工作特征(ROC)曲线,以曲线下面积(AUC)反映诊断的准确性.结果:1)各组血清肿瘤标志检测结果显示,卵巢癌患者HE4,CA125、OPN水平明显高于对照组以及卵巢良性肿瘤组,差异有统计学意义,F值分别为39.23、84.03和104.09,P＜0.01;而卵巢良性肿瘤患者与对照组之间差异均无统计学意义,P＞0.05.2)HE4在不同组织类型卵巢癌中的表达不同,卵巢浆液性癌(95.23％)和内膜样癌(100.00％)中高表达,透明细胞癌(0)和黏液性癌(0)不表达.3)OPN在卵巢癌Ⅲ～Ⅳ期患者中的含量明显高于Ⅰ～Ⅱ期患者,且与肿瘤转移有关,有淋巴结转移患者明显高于无转移者.4)以卵巢良性肿瘤组及卵巢正常组为对照,CA125+ HE4+OPN、CA125+HE4、CA125+OPN、HE4和CA125为盆腔恶性肿瘤诊断指标,ROC曲线下面积依次为0.91.0.90、0.85、0.85和0.80.在特异性为98.3％时,各肿瘤标志诊断盆腔恶性肿瘤的敏感度依次是73.3％、70.0％、66.6％、63.3％和20.0％.特异度为95.0％时,敏感度80.0％、76.6％、70.0％、70.0％和40.0％.特异度是90.0％时,敏感度83.3％、80.0％、76.6％、73.3％和56.6％.结论:CA125+ HE4+OPN3种肿瘤标志联合检测对提高卵巢恶性肿瘤的诊断价值有一定的意义.     

人附睾蛋白4的临床应用进展

人附睾蛋白4(HE4)是一种新型肿瘤标志物,本文从HE4的结构、表达、功能在妇科肿瘤应用,包括其对卵巢癌早期诊断,监测,预后及复发,进行综述,同时对其在肺癌肾纤维化,泌尿系统移行细胞癌中的表达亦进行了综述。最后对目前检测HE4的两种方法酶联免疫吸附法与电化学发光法进行比较。     

Evaluation of ovarian cancer biomarkers HE4 and CA-125 in women presenting with a suspicious cystic ovarian mass

Objective

Women presenting with a large or complex ovarian cyst are referred to extensive surgical staging to ensure the correct diagnosis and treatment of a possible epithelial ovarian cancer. We hypothesized that measurement of the biomarkers HE4 and CA-125 preoperatively would improve the assignment of these patients to the correct level of care.

Methods

Patients diagnosed with a cystic ovarian mass and scheduled for an operation at our center of excellence for ovarian cancer surgery from 2001 to 2010 were prospectively included (n=394) and plasma was collected consecutively. Cut-off for HE4 was calculated at 75% specificity (85 pM and 71.8 pM for post and premenopausal women). For CA-125, 35 U/mL cut-off was used. The study population included women with malignant (n=114), borderline (n=45), and benign (n=215) ovarian tumors.

Results

Receiver operator characteristic (ROC) area under the curve (AUC) in the benign versus malignant cohorts was 86.8% for CA-125 and 84.4% for HE4. Negative predictive value was 91.7% when at least one of the biomarkers was positive, with only early stage epithelial ovarian cancer showing false negative results. Sensitivity at set specificity (75%) was 87% for risk of ovarian malignancy algorithm (ROMA) in the postmenopausal cohort (cut-off point, 26.0%) and 81% in the premenopausal cohort (cut-off point, 17.3%). ROC AUC in the benign versus stage I epithelial ovarian cancer was only 72% for HE4 and 76% for CA-125.

Conclusion

In our study, population HE4 did not outperform CA-125. Based on our data a prospective trial with patients already diagnosed with an ovarian cyst may be conducted.     

Ovarian cancer antigen CA125 is encoded by the MUC16 mucin gene

Serum assays based on the CA125 antigen are widely used in the monitoring of patients with ovarian cancer; however very little is known about the molecular nature of the CA125 antigen. We recently cloned a partial cDNA (designated MUC16) that codes for a new mucin that is a strong candidate for being the CA125 antigen. This assignment has now been confirmed by transfecting a partial MUC16 cDNA into 2 CA125-negative cell lines and demonstrating the synthesis of CA125 by 3 different assays. Of the 3 antibodies (OC125, M11 and VK-8) tested on the transfected cells, only the first 2 were strongly positive, indicating the differential expression of the CA125 epitopes in these cells. The cloning and expression of CA125 antigen opens the way to an understanding of its function in normal and malignant cells.     

HE4与Lewis在卵巢上皮性肿瘤中的表达及相关性研究

目的:研究HE4与Lewis y抗原在卵巢上皮性肿瘤中的表达、相关性及临床意义。方法:免疫组化法检测卵巢上皮性恶性肿瘤、卵巢上皮性交界性肿瘤、卵巢上皮性良性肿瘤及正常卵巢组织中HE4与Lewis y抗原的表达。应用免疫荧光双标记方法检测卵巢上皮性肿瘤中HE4与Lewis y的结构关系。结果:HE4在卵巢恶性肿瘤组的阳性率最高,明显高于良性及正常卵巢组（P均<0.05）。Lewis y表达与HE4相似,在卵巢恶性上皮性肿瘤中,Lewis y抗原的阳性表达率明显高于交界性、良性及正常卵巢组。相关性分析显示:HE4与Lewis y呈直线相关(r=0.813,P<0.05)。在激光共聚焦显微镜下可见HE4与Lewis y抗原有空间位置上的重叠。结论:HE4与Lewis y抗原在卵巢恶性肿瘤中均呈现明显高表达,且两者在卵巢上皮性肿瘤中的表达呈正相关。     

血清CA125、HE4和影像学检查在上皮性卵巢癌术后复发诊断中的应用价值

背景与目的：人附睾蛋白4(human epididymis protein 4,HE4)是一种新型上皮性卵巢癌(epitheli-al ovarian cancer, EOC)的血清免疫标志物。本研究旨在评价其与卵巢最常用的血清标志物—糖类抗原125(cancer antigen-125,CA125)和腹、盆腔CT/MRI检查对卵巢癌术后复发的诊断价值。方法：回顾性分析EOC术后复发患者92例,其中二次手术48例,化疗44例。统计治疗前血清CA125、HE4和腹、盆腔CT/MRI检查诊断的灵敏度,并与手术病理和临床随访结果进行对照。结果：血清CA125和HE4的灵敏度分别为58.7%和61.9%。两者差异无统计学意义(P>0.05);联合两者的灵敏度为80.4%,较单一应用显著提高(P<0.05)。腹、盆腔CT/MRI的灵敏度为88.0%,显著高于血清CA125和HE4(P<0.01)。与两者联用相比,差异无统计学意义(P>0.05)。三者联合应用的灵敏度最高(97.8%),显著高于血清CA125和HE4联用(P<0.01),以及单用腹、盆腔CT/MRI(P<0.05)。结论：血清HE4对于EOC术后复发的检出与CA125同样有效,两者联合应用可显著提高诊断的灵敏度。与腹、盆腔影像学检查三者联用的灵敏度最高,是EOC术后监测较佳的策略。     

卵巢癌血清人附睾分泌蛋白4表达水平的Meta分析

目的：评价血清HE4和CA125在卵巢癌、盆腔良性包块和健康对照者中的表达水平。方法：检索Cochraneli—brary、Medline和CBMDis等数据库,从建库至2011-10关于血清HE4和CA125卵巢癌诊断试验的研究,运用Revman4．2软件对结果进行合并的Meta分析。结果：总共纳入13篇文献,包括卵巢癌652例,盆腔良性肿瘤607例,健康对照644例。血清HE4在卵巢癌中的表达水平为280．11（95％CI：241．83～318．39）ρmol／L,盆腔良性肿瘤为7．71（95％CI：4．66～10．77）ρmol／L;CA125在卵巢癌中的水平为522．54（95％CI：413．51～631．57）U／mL,盆腔良性肿瘤为23．52（95％CI：17．89～29．16）U／mL。HE4和CA125在卵巢癌的表达水平显著高于盆腔良性肿瘤（P〈0．01）,HE4与CA125相比能更好区分盆腔肿瘤的良、恶性。结论：血清HE4在卵巢癌中的表达明显升高并在区分良、恶性方面优于CA125,可作为筛查卵巢癌的肿瘤标志。