Soluble epidermal growth factor receptor (sEGFR) [corrected] and cancer antigen 125 (CA125) as screening and diagnostic tests for epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the leading cause of death among all gynecologic cancers in the United States. Because women who are diagnosed with early stage disease have a better prognosis than women diagnosed with late stage disease, early detection represents a potentially practical approach to reduce the mortality associated with EOC. Unfortunately, no single screening test has proven to be effective for this purpose, and a valid and feasible screening program to detect early stage EOC in the general population has not yet been devised. Consequently, research has focused on coupling two or more screening modalities to improve program validity and feasibility. Serum cancer antigen 125 (CA125) and a soluble isoform of the epidermal growth factor receptor (p110 sEGFR) have been studied individually as biomarkers of ovarian cancer. In this study, we compare serum CA125 levels and sEGFR concentrations in women with EOC to women with benign gynecologic conditions of ovarian and non-ovarian origin. We show that serum sEGFR concentrations are lower in patients with EOC than in women with benign gynecologic conditions, whereas serum CA125 levels are higher in patients to EOC compared with women with benign gynecologic conditions. These data also reveal that age and serum sEGFR concentrations modify the association between CA125 levels and EOC versus benign gynecologic disease. Hence, age- and sEGFR-dependent CA125 cutoff thresholds improve the ability of CA125 to discern EOC patients from women with benign ovarian tumors and non-ovarian gynecologic conditions. Our analyses show that parallel testing with fixed sEGFR and CA125 cutoff thresholds optimizes sensitivity to detect EOC, whereas serial testing with age- and sEGFR-dependent CA125 cutoff thresholds optimizes test specificity, and overall accuracy to discern patients with EOC from women with benign ovarian and non-ovarian gynecologic conditions. The combined use of serologic sEGFR and CA125, thus, has improved utility for screening and diagnosing EOC, which may increase the positive predictive value of a multimodal screening program that incorporates these biomarkers to detect and subsequently differentiate benign from malignant ovarian tumors.     

血清miR-552-5p、HE4及CA125在上皮性卵巢癌中的表达及其临床价值北大核心

目的:探讨miR-552-5p、血清人附睾蛋白4(HE4)及糖类抗原125(CA125)在上皮性卵巢癌(EOC)中的表达及其诊断价值。方法:选取127例EOC患者,90例卵巢良性肿瘤者(良性组)和50例正常对照组作为研究对象,采用实时定量PCR法检测miR-552-5p表达水平,化学发光法测定血清HE4及CA125水平。应用受试者工作特征(ROC)曲线分析miR-552-5p、HE4及CA125诊断EOC的价值。Pearson相关分析EOC患者miR-552-5p表达水平与HE4及CA125的相关性。结果:EOC组血清miR-552-5p(4.25±1.70 vs 1.90±0.83,1.61±0.74)、HE4(350.35±60.12 vs 52.93±11.72,46.80±9.25,pmol/L)及CA125(319.50±96.14 vs 27.14±12.15,20.36±8.95,U/m L)水平均明显高于良性组和对照组(P<0.001)。EOC患者血清miR-552-5p、HE4及CA125表达与临床分期、分化程度及淋巴结转移有关(P<0.05)。ROC曲线显示,miR-552-5p、HE4及CA125三项联合诊断EOC的曲线下面积(0.954,95%CI:0.895~0.998)最大,其敏感度为97.8%,特异度为87.6%。相关分析显示,EOC患者血清miR-552-5p表达水平与HE4及CA125均呈正相关(r=0.872,r=0.805,P<0.001)。结论:血清miR-552-5p、HE4及CA125水平在EOC患者中明显升高,三项联合检测对EOC诊断具有较好的价值。     

血清miRNA-21和miRNA-203在上皮性卵巢癌中的表达及诊断价值

目的 探讨微小核糖核酸21（miR-21）和微小核糖核酸203（miR-203）在上皮性卵巢癌（EOC）中的表达情况,及两者与血清糖类抗原125（CA125）在EOC诊断中的临床价值。方法 采用QPCR检测40例EOC患者（EOC组）、40例上皮性卵巢良性肿瘤患者（良性组）和42例健康女性（正常对照组）血清miR-21和miR-203的表达情况;同时采用电化学发光法检测上述3组人群血清CA125的表达水平;分析miR-21和miR-203的表达与EOC临床病理特征的关系,用受试者工作特征曲线（ROC）评价两者的临床诊断价值并分别计算CA125、miR-21和miR-203单独和联合检测在EOC诊断中的灵敏度和特异度。结果 EOC组miR-21和miR-203的相对表达量分别为2.27±0.48和3.61±0.71,均高于良性组的1.20±0.22和1.47±0.38以及正常对照组的1.00±0.33和1.00±0.28,差异有统计学意义（P＜0.05）;而良性组与正常对照组之间的差异无统计学意义（P＞0.05）。miR-21和miR-203表达与临床分期、淋巴结转移有关（P＜0.05）,与年龄、绝经状态、病理类型和CA125水平无关（P＞0.05）;CA125单独检测的特异度最高,为82.50％;CA125、miR-21和miR-201联合检测的灵敏度最高,达95.00％。结论 miR-21和miR-203可能在EOC的发生、发展中发挥原癌基因的作用;血清CA125、miR-21和miR-203三者联合检测可提高EOC诊断的灵敏度。     

Clinical value of serum tumor supplied group of factor in diagnosis of epithelial ovarian cancer

Tumor supplied group of factor (TSGF), whose original name was tumor specific growth factor, is a new tumor marker associated with vascular proliferation of malignant tumor. We investigated the correlation of the serum level of TSGF with VEGF and CA125 in patients with epithelial ovarian cancer and benign ovarian lesion, and compared their clinical diagnostic value for epithelial ovarian cancer. MATERIALS AND METHODS Clinical Materials During the period from Sep. 1997 to Sep…     

miR-506和FGF2在上皮性卵巢癌中的表达及临床意义

目的:检测上皮性卵巢癌组织微小RNA-506（miR-506）和成纤维细胞生长因子2（FGF2）表达情况,并探究其临床意义。方法:选取2011年3月至2012年12月本院收治的上皮性卵巢癌患者56例,选择同期因子宫良性病变在平煤神马医疗集团总医院接受全子宫双附件切除的患者56例（对照组）;采用实时定量PCR（qRT-PCR）法检测miR-506表达水平,采用免疫组化法检测FGF2表达水平,采用全自动化学发光免疫分析仪检测血清糖类抗原125（CA125）水平。结果:上皮性卵巢癌组织miR-506表达水平较正常卵巢组织显著降低（P＜0.05）,FGF2表达量显著高于正常卵巢组织（P＜0.05）,FGF2蛋白表达阳性率较正常卵巢组织显著升高;上皮性卵巢癌组织中miR-506、FGF2表达与患者临床分期、有无淋巴结转移、血清CA125水平有关（P＜0.05）,与患者年龄、组织学类型无关（P＞0.05）;miR-506高表达上皮性卵巢癌患者术后5年总生存率显著高于低表达者（P＜0.05）,FGF2高表达上皮性卵巢癌患者术后5年总生存率显著低于低表达患者（P＜0.05）;Pearson检验结果显示,卵巢癌肿瘤组织miR-506与FGF2表达水平负相关。结论:miR-506在上皮性卵巢癌组织中低表达,FGF2高表达,与患者临床分期、淋巴结转移、血清CA125水平有关,可能作为上皮性卵巢癌患者病情监测及预后的生物指标。     

Impact of Preoperative Serum Levels of CA 125 on Epithelial Ovarian Cancer Survival

Background: CA125 is very helpful in treatment monitoring and detection of epithelial ovarian cancer (EOC) recurrence. However there is controversy as to its accuracy and optimal usage. What is the impact of the CA125 levels before primary surgery treatment to the survival of patients? This study aimed to detect any association of preoperative serum levels with prognosis and survival in EOC patients. Materials and Methods: Our cohort comprised EOC patients in Dr. Sardjito Hospital, Yogyakarta, Indonesia, who complied with follow up. To explore the effect of preoperative CA125 levels and other variables on survival Cox's regression models were applied. Results: A total of 90 cases of EOC who had surgery were available for follow up. The level of CA125 poroved to be a prognostic factor for overall survival of EOC patients, with an adjusted HR of 4.10 (p = 0.03). Adjuvant chemotherapy was another prognostic factor, 1 - 2 cycles having an adjusted HR of 0.17 (p = 0.04) and 3 - 8 cycles HR 0.39 (p = 0.06). Other factors such as age of patients adjusted HR 1.54 (p = 0.32), moderate differentiation (adjusted HR 1.61, p = 0.51) poor differentiation (adjusted HR 3.41, p = 0.15), and stage of disease (adjusted HR 1.98, p = 0.27) were statistically not significant. However, this might have been because the power of the study was low. Conclusions: Preoperative level of CA125 is a prognostic factor for overall survival in EOC patients. The best cut-off for prognostic classification of CA125 serum level is 70 U/ml.     

Diagnostic Model of Serum miR-193a-5p,HE4 and CA125 Improves the Diagnostic Efficacy of Epithelium Ovarian Cancer

Epithelium ovarian cancer (EOC) is currently the prevalent malignant cancer worldwide. However, there is a lack of efficient biomarkers for EOC screening. Accumulating evidence reveals that serum miRNA detectable in various types of cancer. Therefore, we explore the diagnostic value of combined detection of plasma miR-193a-5p, HE4 and CA125 for EOC. Serum samples were collected from 45 patients with primary EOC, 30 patients with benign ovarian tumor patients and 40 healthy controls. The expression of serum miR-193a-5p was detected by real-time quantitative PCR, and serum HE4 and CA125 were detected by chemiluminescent immunoassay. Moreover, a diagnostic model combining miR-193a-5p, HE4 and CA125 or alone in EOC patients was evaluated by ROC curve analysis. The relative expression quantity (RQ) of serum miR-193a-5p in EOC patients, benign ovarian tumor patients and healthy control groups were 0.419 (0.093, 2.215), 3.667 (1.633, 6.691) and 1.130 (1.000, 7.087), respectively. The RQ of serum miR-193a-5p in EOC patients was significantly lower than that in benign ovarian tumor patients and healthy controls (both P?<?0.001), and there was no significant difference between benign ovarian tumor patients and healthy controls (both P?>?0.05). There was no significant correlation between serum miR-193-5p, HE4 and CA125 levels (both P?>?0.05). Additionally a risk model for miR-193a-5p, HE4 and CA125 was correlated with Grading and Lymph node metastasis (P?=?0.016, P?=?0.029). The area under the receiver operating characteristic curve of a risk model for distinguishing EOC patients from healthy individuals was 0.996, which higher than any single biomarker. Combined detection of miR-193-5p, HE4 and CA125 by logistic regression analysis could greatly improved the diagnostic ability of EOC and may prove to be a candidate biomarker, providing new directions for further investigation.     

检测卵巢上皮性肿瘤患者血清和肿瘤组织中VEGF的临床意义

背景及目的:本研究拟通过对卵巢上皮性肿瘤患者血清血管内皮生长因子(vascularepithelialgrowthfactor,VEGF)水平的检测及对卵巢上皮性肿瘤组织中VEGF表达的观察,以探讨VEGF与卵巢上皮性肿瘤临床、病理诸因素的关系。方法:卵巢上皮性肿瘤患者73例,其中24例为良性肿瘤患者(良性组),7例为交界性上皮瘤患者(交界性组),42例为恶性肿瘤患者(恶性组);以同期在本科室查体无明显妇科疾患的20名妇女血清做对照。用免疫组化二步法检测73例卵巢上皮性肿瘤患者肿瘤组织中VEGF的表达,用ELISA法测定71例卵巢上皮性肿瘤患者术前血清及10例患者腹水中VEGF水平,对其中7例卵巢上皮性癌患者血清在术后进行了定期检测。结果:①VEGF在卵巢上皮性肿瘤组织中的表达,恶性组阳性表达率(86.36%)明显高于交界性组(66.67%,P<0.005)及良性组(37.50%,P<0.005)。②良性组、交界性组及恶性组之间血清VEGF水平的差异有统计学意义(P<0.01);在恶性组中,血清VEGF水平在临床Ⅲ、Ⅳ期明显高于Ⅰ、Ⅱ期(P<0.05),在病理分化差的G3组明显高于病理分化好的G1、G2组(P<0.01),而与病理类型相关性无统计学意义;卵巢癌患者经理想的肿瘤细胞减灭术后,血清VEGF水平均有不同程度下降,有3例患者病情复发后,血清VEGF水平再度上升。结论:①VEGF在卵巢上皮性肿     

血管内皮生长因子、p53在卵巢上皮癌中表达的临床意义

目的:探讨血管内皮生长因子(VEGF)和癌基因p53在卵巢上皮癌表达的相关性及其与卵巢上皮癌临床病理因素的关系以及对卵巢癌患者预后的影响。方法:用免疫组化二步法检测73例卵巢上皮肿瘤组织中VEGF、p53蛋白的表达(良性上皮瘤24例,交界性上皮瘤7例,上皮性癌42例)。结果:VEGF在卵巢上皮肿瘤组织中的表达,恶性组阳性表达率(86.36 %)明显高于交界性组(66.67 %)及良性组(37.50 %)(P<0.005);在恶性组中,VEGF表达在不同的病理分级、临床分期中无明显差异(P>0.05)。p53在卵巢上皮肿瘤组织中的表达,恶性组阳性表达率(76.19 %)明显高于交界性组(28.57 %)及良性组(9.09 %)(P<0.01)。在恶性组中临床晚期患者p53阳性表达率(89.29 %)高于早期患者(50.00 %)(P<0.01);在不同的病理分级中p53阳性表达率无明显差异。VEGF与p53在卵巢上皮癌中的表达呈正相关,(r =0.571 4,P<0.01)。VEGF、p53表达双阴性患者的3 a生存率66.7 %(2/3)明显高于VEGF 、p53表达双阳性患者20.00 %(5/25)。结论:VEGF与p53表达呈正相关,和卵巢癌生物学特性有关,可作为估计卵巢癌预后的重要因素。     

Role of HE4, CA72.4, and CA125 in monitoring ovarian cancer

The aim of this study was to investigate the role of biomarkers CA125, HE4, and CA72.4 at diagnosis and throughout the follow-up in patients with epithelial ovarian cancer (EOC). Thirty-nine patients with EOC were deemed eligible, and 20 were followed up. CA125, HE4, and CA72.4 serum levels were determined for all patients at initial diagnosis of EOC. Among these patients, the number of cases with an elevated level of each individual marker was CA125 77?%, HE4 85?%, and CA72.4 72?%. A statistically significant difference was observed between the level of HE4 when compared to CA72.4 (p?<?0.02). In the follow-up phase, we observed tumor marker levels fluctuating according to response to chemotherapy. When combining two out of the three biomarkers together, we observed increased values of CA125 and CA72.4 in 55?% of the patients, increased values of CA125 and HE4 in 65?% of the patients, and finally increased HE4 and CA72.4 in 75?% of the patients. A statistically significant difference was observed when combining HE4 and CA72.4, but not CA125 and CA 72.4 (p?<?0.002). In conclusion, our study demonstrates that the association of three biomarkers CA125, HE4, and CA72.4 provides a valuable contribution in the follow-up of EOC patients.     

Serum HE4 superior to CA125 in predicting poorer surgical outcome of epithelial ovarian cancer

Epithelial ovarian cancer (EOC) remains the deadliest form of gynecological cancers. Optimal tumor debulking, no matter the primary or the interval, is the most important prognostic factor for EOC, so there is an urgent demand for biomarkers to predict surgical outcome. The aim of this study was to investigate whether serum human epididymis protein 4 (HE4) and cancer antigen 125 (CA125) could predict surgical outcome of EOC. The levels of preoperative serum HE4 and CA125 were determined by electrochemiluminescence (ECLIA) in 82 EOC patients, comprising 39 subjected to primary debulking surgery (PDS) and 43 with extensive stage III or IV disease to neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS). Among 39 patients subjected to primary debulking surgery, HE4 was superior to CA125 in predicting surgical outcome (area under curve [AUC] 0.758 vs. 0.633). At a cutoff of 353.22 pmol/L, HE4 reached 77.4 % in sensitivity and 75 % in specificity. The prediction of surgical outcome of interval debulking surgery based on preoperative HE4 and CA125 values was performed in 43 patients who received NACT-IDS. The difference of AUC between HE4 and CA125 (0.793 vs. 0.663) indicating that HE4 was the better biomarker to predict surgical outcome of IDS. A pre-IDS HE4 value of 154.3 pmol/L is the optimal cutoff to identify patients who would not benefit from IDS with a sensitivity of 92.9 % and a specificity of 69 %. The change (>70 %) of HE4 before and after neoadjuvant chemotherapy could predict optimal interval debulking surgery. Serum HE4 was superior to CA125 in predicting surgical outcome of primary debulking surgery and interval debulking surgery. The change (absolute value or percentage) of HE4 in neoadjuvant chemotherapy could predict the outcome of interval debulking surgery.

     

非小细胞肺癌血清VEGF与CA125 CEA Cyfra21-1 的相关性及临床意义*

目的：探讨化疗前血清血管内皮生长因子（VEGF）检测在非小细胞肺癌（NSCLC ）中的临床应用价值,同时测定血清中CA125、CEA 、Cyfra21-1 的滴度及其相关性。方法：采用抗人VEGF单克隆抗体、夹心ELISA 法测定78例NSCLC 患者血清VEGF浓度。同时利用放射免疫法检测血清中CEA 、CA125、Cyfra21-1 的浓度。结果：NSCLC 有远处转移组血清VEGF、CA125、CEA 浓度显著高于无远处转移组（P<0.05）;有淋巴结转移组血清VEGF显著高于无淋巴结转移组（P<0.05）。 血清VEGF和CA125、CEA 在Ⅲ+ Ⅳ期NSCLC 的表达显著高于I+II 期NSCLC（P<0.05）。 血清CEA 在腺癌中显著增高（P<0.05）。 血清VEGF、CA125 阴性组的化疗有效率（35.3% 、35.7%）显著高于阳性组（7.7% 、15.8%）（P=0.004,0.006）。 化疗前血清CEA 阴性者的中位总生存时间（mOS ）较阳性者明显延长（分别为36个月,20个月;P=0.04）;而血清VEGF、Cyfra21-1、CA125 浓度对mOS 无明显影响（P 值分别为0.07,0.099,0.19）。 血清CEA 、VEGF、Cyfra21-1、CA125 表达对中位无瘤生存期（mTTP）均无明显影响（P 值分别为0.119,0.280,0.146,0.230）。 NSCLC 患者血清VEGF 与CEA 表达存在显著正相关（P<0.05）,其他肿瘤标志物之间无显著相关性（P>0.05）。 结论：综合检测NSCLC 患者化疗前血清肿瘤标志物可能有利于协助诊断、预测转移、评价化疗疗效及判断预后。     

Tissue CA125 and HE4 Gene Expression Levels Offer Superior Accuracy in Discriminating Benign from Malignant Pelvic Masses

Background: Ovarian cancer remains a major worldwide health care issue due to the lack of satisfactory diagnostic methods for early detection of the disease. Prior studies on the role of serum cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) in detecting ovarian cancer presented conflicting results. New tools to improve the accuracy of identifying malignancy are urgently needed. We here aimed to evaluate the diagnostic utility of tissue CA125 and HE4 gene expression in comparison to serum CA125 and HE4 in discriminating benign from malignant pelvic masses. Materials and Methods: One-hundred Egyptian women were enrolled in this study, including 60 epithelial ovarian cancer (EOC) patients and 20 benign ovarian tumor patients, as well as 20 apparently healthy women. Preoperative serum levels of CA125 and HE4 were measured by immunoassays. Tissue expression levels of genes encoding CA125 and HE4 were determined by quantitative real time polymerase chain reaction (qRT-PCR). The diagnostic performance of CA125 and HE4, measured either as mRNA or protein levels, was evaluated by receiver operating characteristic (ROC) curves. Results: The serum CA125+HE4 combination and serum HE4, with area under the curve (AUC) values of 0.935 and 0.932, respectively, performed significantly better than serum CA125 (AUC=0.592; P<0.001). Tissue CA125 and HE4 (AUC=1) performed significantly better than serum CA125 (P<0.001), serum HE4 (P=0.016) and the serum CA125+HE4 combination (P=0.018). Conclusions: Measurement of tissue CA125 and HE4 gene expression not only improves discriminatory performance, but also broadens the range of differential diagnostic possibilities in distinguishing EOC from benign ovarian tumors.     

Difference in mesothelin‐binding ability of serum CA125 between patients with endometriosis and epithelial ovarian cancer

The epithelial ovarian carcinoma (EOC) is an aggressive malignant tumor, and is currently the leading cause of gynecologic cancer death. CA125 is the most commonly used serum marker for EOC, but shows a high‐false‐positive rate for several benign diseases such as endometriosis. The purpose of our study is therefore to identify a useful biochemical tool for detecting qualitative differences between CA125 from patients with endometriosis and EOC, and to facilitate differential diagnosis of these diseases. In our study, using two different CA125‐binding molecules, i.e., recombinant mesothelin and an anti‐CA125 monoclonal antibody, a novel sandwich ELISA for determining the serum levels of CA125 with mesothelin‐binding ability (CA125^meso) was developed, and tested for patients with endometriosis (n = 59) and EOC (n = 36). We found that both the serum CA125^meso level and the ratio of the serum CA125^meso to CA125 levels (CA125^meso/CA125) were significantly higher in patients with EOC than in patients with endometriosis (p < 0.00005 and p < 0.000001, respectively). Furthermore, receiver operating characteristic analysis showed that the CA125^meso assay was superior to the conventional antibody‐based CA125 assay in discriminating endometriosis from EOC. Thus, mesothelin‐binding ability may be a useful indicator for qualitatively evaluating CA125 in patients with endometriosis and EOC.     

Concentration of vascular endothelial growth factor (VEGF) in the serum of patients with suspected ovarian cancer.

As a promoter of angiogenesis, vascular endothelial growth factor (VEGF) is believed to play a pivotal role in tumour growth and metastasis. The aim of this study was to determine the value of preoperative serum VEGF levels in the early diagnosis of ovarian cancer and in the differential diagnosis of adnexal masses. We examined preoperative serum VEGF levels in healthy women (n = 131), patients with benign ovarian cysts (n = 81) and in ovarian cancer patients (n = 44) by using an ELISA (R&D Systems, Minneapolis, MN, USA). A logistic regression model was carried out to determine the influence of VEGF and CA 125 on the probability of malignancy. VEGF revealed a significant influence on the odds of presenting with malignancy vs healthy women (P = 0.001). At 363.7 pg ml(-1), VEGF achieved a sensitivity of 54% and a specificity of 77%. With respect to the differentiation between benign cysts and ovarian cancer, CA 125 (P < 0.0001) but not VEGF (P = 0.229) predicts the presence of malignancy in a multivariate model. In conclusion, VEGF does not appear to be a useful tool in the early diagnosis of ovarian cancer or for indicating the absence or presence of malignancy in patients with an adnexal mass.     

The prognostic value of pretreatment CA 125 in patients with advanced ovarian carcinoma

BACKGROUND:

The objective of the current study was to determine the prognostic significance of a pretreatment serum CA 125 level in patients with advanced epithelial ovarian carcinoma (EOC) who received treatment with a standard chemotherapy regimen.

METHODS:

Patients with International Federation of Gynecology and Obstetrics stage III/IV ovarian carcinoma who were on 1 of 7 Gynecologic Oncology Group (GOG) phase 3 trials and received treatment with a standard regimen of intravenous cisplatin and paclitaxel were included. A Cox regression model was used to assess the impact of CA 125 levels drawn before the initiation of chemotherapy on progression‐free survival (PFS) both overall and by subgroup, including surgical debulking status, disease stage, and histologic subtype.

RESULTS:

In total, 1299 patients who were on the cisplatin/paclitaxel arms of the GOG trials were eligible. The median CA 125 level was 246 U/mL. Only 7.6% of patients had a normal CA 125 level (≤35 U/mL). The lowest median CA 125 level was observed in the group with mucinous tumors; however, 69% of women who had mucinous tumors had abnormal CA 125 levels. Shorter PFS was observed with increasing CA 125 and persisted in multivariate analysis. Overall and in the serous subgroup, a 1‐fold increase in CA 125 level was associated with a 7% increase in the hazard of disease progression (P < .001). This association was even more pronounced in patients who had stage III disease that was debulked to microscopic disease (15%; P = .003) and in patients who had endometrioid tumors (17%; P = .001).

CONCLUSIONS:

A normal CA 125 level in the setting of advanced EOC was rare even after surgical debulking. The pretreatment CA 125 level was an independent predictor of PFS in patients with advanced EOC who received a standard chemotherapy regimen, particularly in the setting of disease that was debulked to a microscopic residual and in the serous or endometrioid subtypes. Cancer 2009. © 2009 American Cancer Society.     

卵巢癌患者手术及化疗前后CA125的变化与抗体芯片筛选差异蛋白的关系

目的动态检测了卵巢癌患者CA125的水平，了解患者在手术前、手术后及全程化疗结束后CA125变化，并分别与前期研究所作的相同患者血清抗体芯片结果进行比较，以期发现相关规律，为评估机体内卵巢癌细胞的消长提供重要的参考资料。方法分别于手术前，手术后和化疗结束后3个时间点动态检测患者血清的CA125。结果卵巢上皮性癌患者3个时间点的CA125变化很明显，术前增高，随着手术和化疗的结束，CA125显著下降。三组抗体芯片共筛选出8个与肿瘤细胞消长有关的差异性蛋白质。结论共有8个差异表达蛋白（RAP1A、p53、TGF-β1、G3BP、BAK1、CASP6、FADD和LZPTS1）可能会成为评估卵巢癌细胞在体内的消长情况的新指标。     

Cell-free 59 kDa immunoreactive integrin-linked kinase: a novel marker for ovarian carcinoma.

PURPOSE: We reported that the expression of integrin-linked kinase (ILK) is up-regulated in ovarian carcinomas and that ovarian cancer cells have high expression of ILK. In this study, we have examined the expression of cell-free 59 kDa immunoreactive (ir)ILK in the serum and peritoneal fluid (PTF) of patients with ovarian cancer and evaluated its potential as a serum biomarker for early-stage screening and for monitoring clinical status of patients after chemotherapy treatment. EXPERIMENTAL DESIGN: Thirty-six serum specimens, including normal (n = 6), benign (n = 6), borderline (n = 4), grade 1 (n = 5), grade 2 (n = 5), and grade 3 (n = 10), were evaluated for the expression of irILK by Western blotting. The expression of irILK was evaluated in PTF (n = 10) and peritoneal washings from women with benign ovarian cysts (n = 4). In addition, tissue-conditioned medium obtained from the cultures of primary ovarian tumors (n = 9) was examined for the presence of irILK. Finally, the potential of serum irILK as a biomarker for ovarian cancer screening was evaluated by comparison with cancer antigen 125 (CA 125) concentrations in cancer patients before and after chemotherapy. RESULTS: irILK expression was present in normal serum and in serum of patients with benign ovarian tumors. irILK expression was 6-9-fold higher in the serum of patients with grade 1, grade 2, and grade 3 ovarian cancer than in the serum of healthy volunteers and patients with benign ovarian tumors (P < 0.01). Enhanced expression of irILK in the serum of ovarian cancer patients correlated with the concentration of CA 125. High expression of irILK was present in all 10 PTF tested. Tissue-conditioned medium prepared from malignant ovarian tumors had 4-fold more irILK expression than conditioned medium obtained from borderline and benign tumors (P < 0.01). irILK expression in serum of cancer patients was reduced to basal normal levels after six cycles of Taxol/carboplatin and was consistent with the change of CA 125 levels before and after chemotherapy. CONCLUSIONS: These data suggest that irILK is an ovarian tumor-associated antigen and implicates its potential not only as a biomarker for early-stage screening but also as a marker for monitoring the clinical condition of patients after treatment.     

GCDFP-15对乳腺癌卵巢转移的诊断价值

目的 探讨特异性大囊肿病液体蛋白-15 (gross cystic disease fluid protein-15, GCDFP-15)和mammaglobin在乳腺癌卵巢转移诊断中的价值。方法 收集1995年11月～2007年12月我院收治的4704例乳腺癌中12例经病理证实的乳腺癌卵巢转移患者及10例乳腺和卵巢双原发癌患者的临床病理资料,以免疫组织化学法探讨最具有鉴别诊断价值的分子标志。结果 乳腺癌卵巢转移患者的中位年龄为45岁[（28～53)岁]。在诊断卵巢转移之前,12例(100％)均有卵巢外转移。该病术前影像学检查阴性者为9例（75％）,术前漏诊率亦高达75％。乳腺癌发生卵巢转移以双侧多见(9例),仅表现为镜下转移的占75％。乳腺癌卵巢转移患者的GCDFP-15和mammaglobin的表达较卵巢原发上皮性癌患者的高,分别是75％、0(P＜0.001)和50％、0(P＝0.033),差异有统计学意义。血清学检查乳腺癌卵巢转移患者和乳腺、卵巢双原发癌患者的CA153、CA125均有上升,但CA153数值无差异（128.6u/mlvs.56.48u/ml,P＝0.315CA125在乳腺癌卵巢转移患者轻微升高,中位数值81.88u/ml [（47.15～966.9)u/ml],在卵巢原发癌患者中明显升高,中位数值1073u/ml [（134.3～1821)u/ml],差异有统计学意义（P＝0.003）。结论 乳腺癌卵巢转移常见于绝经前年轻女性患者,且大部分患者在出现卵巢转移以前已经有其他部位的转移。卵巢转移病变一般非常微小,通常是镜下转移,术前容易被误诊或漏诊;免疫组织化学联合检测特异性分子GCDFP-15、mammaglobin、WT1和CA125有助于与原发性卵巢癌相鉴别,卵巢双侧病变及血清CA125的轻微上升也有助于诊断乳腺癌的卵巢转移。