The concomitant determination of different serum tumor markers in epithelial ovarian cancer: relevance for monitoring the response to chemotherapy and follow-up of patients.

The levels of CA125, CA19.9, CA15.3 CA72.4, and TATI were serially measured during and after chemotherapy in 43 patients with epithelial ovarian cancer having elevated concentrations of one or more of the antigens before initial surgery. The value of 35 U/ml was chosen as cutoff level of CA125 for the monitoring of disease. Changes in the serum levels of CA125, CA19.9, CA15.3, CA72.4, and TATI correlated with the clinical course of disease in 87.4% of 215, 76.3% of 80, 71.3% of 122, 76.0% of 167, and 48.5% of 101 instances, respectively. After the sixth course of monthly primary chemotherapy, elevated antigen levels were strong predictors of persistent disease, while normal antigen values were associated with both positive and negative second-look findings. It is worth noting that antigen levels above the cut-off limits before the third course, but still in the normal range after the sixth course, seemed to be predictive of positive second-look findings. Among patients with elevated antigen levels at diagnosis, clinical detection of neoplastic progression after treatment was stopped was preceded by an elevation of serum CA125 in 93.3% of 15 patients, of serum CA19.9 in 80.0% of 5 patients, of serum CA15.3 in 66.7% of 9 patients, of serum CA72.4 in 81.8% of 11 patients, and of serum TATI in 40% of 10 patients. In patients with positive CA125 assay at diagnosis, the concomitant evaluation of the other antigens did not seem to be of additional benefit for monitoring epithelial ovarian cancer. However, the measurement of the other tumor markers could represent an interesting biochemical tool for the management of patients with negative CA125 assay. In particular the evaluation of serum CA19.9 or CA72.4 could be very useful in the monitoring of patients with mucinous ovarian cancer, which often fails to express CA125 antigen.     

Immunohistochemical localization of tumor markers in epithelial ovarian cancer

Immunohistochemical determinations of carcinoembryonic antigen, alpha-fetoprotein, human chorionic gonadotropin (hCG), and human placental lactogen (hPL) were performed on tissue sections from 137 epithelial ovarian cancers. Fewer than 25% of serous cystadenocarcinomas contained detectable amounts of any marker. Carcinoembryonic antigen was present in over 50% of tumors, and was noted most frequently in mucinous, endometrioid, and clear cell carcinomas. hPL was demonstrated in 30% of endometrioid carcinomas but was rarely present in other cell types. Both alpha-fetoprotein and hCG were noted in fewer than 10% of all major cell types of epithelial ovarian cancer. Forty-five patients had serial determinations of plasma levels of carcinoembryonic antigen at the time of regular follow-up visits. Serial plasma levels of carcinoembryonic antigen accurately predicated recurrence in nine of 16 patients whose tumors contained carcinoembryonic antigen, in contrast to two of 16 patients whose tumors were devoid of antigen.     

卵巢上皮性癌血清肿瘤标志物谱变化的临床意义

目的 探讨卵巢上皮性癌(卵巢癌)患者化疗后肿瘤标志物谱的变化及其潜在的临床意义.方法 选择1999年1月至2007年7月期间经肿瘤细胞减灭术及规范化疗的卵巢癌患者102例,对其术前、术后、每次化疗前、随访期间和复发前后的血清肿瘤标志物CA125、CA19-9和CP2的水平进行检测、分析,其中48例患者的肿瘤标志物记录完整而纳入分析,复发患者为28例,初治化疗患者20例(均为耐药病例).根据肿瘤标志物谱变化与否,分别将复发和初治化疗患者分为肿瘤标志物谱变化组与未变化组.平均随访时间为25个月.结果 (1)肿瘤标志物谱的主要变化表现为标志物的数最变化和(或)标志物的种类改变.28例复发患者中肿瘤标志物谱发生变化者占46%(13/28),20例初治化疗患者中标志物谱发生变化者占45%(9/20).(2)肿瘤标志物谱变化的复发患者中,病理类型以浆液性癌所占比例最高,为77%(10/13),而初治化疗患者中,以黏液性癌所占比例最高,为4/9.(3)复发患者肿瘤标志物谱变化组的无疾病进展期和中位总生存时间分别为22.2、60.0个月,较未变化组(分别为17.4、46.0个月)明显延长(P均<0.05);初治化疗患者肿瘤标志物谱变化组的中位总生存时间较未变化组(分别为15.9、25.0个月)明显缩短(P<0.05).结论 卵巢癌化疗期间和复发后肿瘤标志物谱可发生变化,化疗及随访期间应对肿瘤标志物进行联合检测.     

术前测定血清CA125、CA199、CA724、CEA和GM-CSF在鉴别附件包块性质中的作用

探讨术前测定患者血清CA12 5、CA19 9、CA72 4、CEA和GM -CSF水平在鉴别附件包块良恶性质中的作用。方法 :74例附件包块患者术前 1周内采外周血 ,用固相免疫放射法测定各种肿瘤标志物浓度 ,并与术后组织学诊断比较。计算各标志物单独和联合应用诊断卵巢癌的相应诊断参数。结果 :( 1)CA12 5(临界值 70U/ml)鉴别卵巢肿瘤性质的敏感性和特异性分别为 85 71%和 82 61% ,CA19 9(临界值 30U/ml)分别为 4 2 86%和 73 33% ,CA72 4 (临界值 3 8U/ml)分别为 53 57%和 90 90 % ,CEA(临界值 5ng/ml)分别为 4 6 4 3%和 4 8 89% ;( 2 )联合应用肿瘤标志物 :CA12 5联合CA19 9的敏感性和特异性分别为 89 2 9%和 73 33% ;CA12 5联合CA72 4的敏感性和特异性分别为 89 2 9%和 75 56% ;CA12 5联合CEA的敏感性和特异性分别为 92 86%和 4 0 0 0 % ;( 3)如果去除 9例子宫内膜异位症 ,CA12 5、CA19 9、CA72 4和CEA的特异性分别增至 89 19% ,80 55% ,94 2 9%和4 7 2 2 %。结论 :此项研究应用的肿瘤标志物中以CA12 5最为敏感。将CA12 5临界值定为 70U/ml时诊断效果最佳。CA72 4的特异性最高 ,但诊断卵巢癌的敏感性低。CEA的诊断价值有限 ,GM -CSF则无价值。CA12 5与其他肿瘤标志物联合检测时诊断的特异性会部分丧失。?     

Sonographic characterization, Doppler ultrasonography and tumor markers in the diagnosis of malignancy of ovarian masses

BACKGROUND: The study analyses the diagnostic possibilities regarding ovarian neoplasms offered by different clinical approaches: B-mode morphological ultrasonographic examination, colour Doppler and Doppler pulsed ultrasonography, and lastly the assay of a number of tumour markers. METHODS: A prospective study was carried out in 125 selected patients attending the Ultrasonography unit of the Obstetrics and Gynecology Clinic at Parma University between June 1997 and June 1999 who presented an adnexal mass . All patients underwent transvaginal ultrasonography (multifrequency vaginal probe 5.0-6.5 MHz, Esaote Idea, Genova) to characterise the mass, applying 5 different ultrasonographic scores: Granberg, Sassone, Di Priest, Lerner, Ferrazzi. Colour Doppler imaging was then performed to analyse the vascularisation of the mass, also using pulsed Doppler to study a number of velocimetric parameters: pulsatility index, index of resistance, systolic and diastolic peak velocity, mean velocity. All the patients underwent surgery using laparotomy or video laparoscopy, accompanied by histological analysis. A number of different tumour markers were assayed prior to surgery: Cal25, CA19-9, CEA, beta-HCG, alpha-fetoprotein. RESULTS: Out of 127 pelvic masses examined, histological analysis showed that 19 were malignant and 108 benign. The diagnostic accuracy of malignancy was comparable for the 5 scores studied, with a minimum of 57.48% for Lerner and a maximum of 77.16% for Di Priest. The central importance of vascularisation was the only significant parameter among those analysed using colour Doppler which was useful for the diagnosis of a malignant neoplasm, with a diagnostic accuracy of 82.95%. No indicator obtained using pulsed Doppler was useful for diagnostic purposes. CA125 was the only tumour marker that revealed a statistically significant difference emerged between the benign (21.6 U/ml) and malignant (220.8 U/ml) masses. Its diagnostic accuracy was 75.58%. CONCLUSIONS: This study confirmed that the three methods analysed do not differentiate substantially in their overall diagnostic capacity of malignant ovarian neoplasms. The best performances for ecographic scores (Di Priest) did not exceed a sensitivity of 89.47% with a 21.25% incidence of false positives; this was comparable to CA125 with a sensitivity of 85.71% and false positives in 22.09%. In relation to the central importance of vascularisation, colour Doppler achieved a lower sensitivity (55.55%), but this was confirmed by a low incidence of false positives (7.95%). This revealed its importance as a useful method, especially for excluding the presence of malignant tumours.     

Serum C-reactive protein in the differential diagnosis of ovarian masses

Objective

A number of serum tumor markers have been investigated to aid clinicians in the differential diagnosis of ovarian masses. Serum C-reactive protein (CRP) is a widely used biomarker of inflammation and has been previously shown to be a promising biomarker in patients with ovarian cancer.

Study design

In a retrospective single-center study, we evaluated serum CRP in 576 patients with benign and in 242 patients with malignant (ovarian tumors of low malignant potential [LMP]: n = 44, epithelial ovarian cancer [EOC]: n = 198) ovarian masses. Results were correlated to clinical data.

Results

Median (25th, 75th percentiles) serum CRP in patients with benign ovarian tumors, with ovarian tumors of LMP, and with EOC were 0.5 (0.5, 0.6) mg/dL, 0.5 (0.5, 0.9) mg/dL, and 1.36 (0.5, 4.9) mg/dL, respectively (p < 0.001). In the subgroup of patients with EOC, serum CRP significantly correlated with FIGO stage (p < 0.001), residual tumor mass (p < 0.001), and patients’ age (p = 0.04), but not with tumor grade (p = 0.2) and histologic type (p = 0.4). In univariable and multivariable models including serum CRP, serum CA 125, and patients’ age, serum CRP independently predicted the presence of malignant ovarian masses (p < 0.0001; Odds Ratio [OR] 5.3, 95% Confidence Interval [CI] 3.8–7.4). Serum CRP had a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for identifying malignant ovarian masses of 49.8%, 84.1%, 57.1%, and 79.8%, respectively.

Conclusion

Serum CRP is associated with the presence of malignant ovarian tumors independent of serum CA 125 and patients’ age and can therefore be used as additional diagnostic marker in the differential diagnosis of ovarian masses.     

肿瘤标志物预测卵巢癌预后的价值

对卵巢癌预后进行准确预测是个体化治疗的基础和推动力。无论蛋白还是非编码RNA,都有作为卵巢癌预后预测因子的潜能。已经研究证实其中的一些肿瘤标志物与卵巢癌的总生存、无进展生存和（或）化疗反应性密切相关,但在用于临床之前还需要进一步验证。     

Pretreatment serum levels of CA-125, carcinoembryonic antigen, tissue polypeptide antigen, and placental alkaline phosphatase, in patients with ovarian carcinoma, borderline tumors, or benign adnexal masses: relevance for differential diagnosis

Pretreatment serum levels of the antigens CA-125, tissue polypeptide Antigen (TPA), carcinoembryonic antigen (CEA), and placental alkaline phosphatase (PLAP) were determined in samples from 295 women with adnexal masses. At laparotomy 48% of patients had epithelial ovarian carcinoma, 9% had tumors of low malignant potential, and 8% suffered from malignancies of other kinds. The sensitivity of CA-125 with 35 U/ml as the cutoff was 88% in women with ovarian carcinoma, but 74% among those with limited disease and 58% in borderline malignancy. Only 6 of 17 mucinous ovarian carcinomas were detected. Specificity was 83%. CEA was elevated above 5.0 micrograms/liter in 15 of 17 patients with mucinous ovarian cancer. TPA detected advanced stages of malignancy, but the sensitivity was low, 53%, in cases with limited disease. PLAP was elevated in 46% of ovarian carcinoma patients. For detecting malignancy overall, the use of a parallel combination of the CA-125 and CEA assays was more sensitive than use of CA-125 as a single marker. This test combination may be of value in the diagnosis of adnexal masses. The predictive value of a positive result was 90%, and that of a negative result, 76%.     

Peritoneal fluid analysis in the differentiation of ovarian cancer and benign ovarian tumor.

PURPOSE: The aim of the study was to try to identify the biochemical markers in peritoneal fluid which might be useful in discrimination between ovarian cancer and benign ovarian tumor. METHODS: The study included 75 patients: 43 with invasive ovarian cancer, 6 with borderline ovarian cancer and 26 with benign ovarian tumor. The peritoneal fluid samples from all these patients were subjected to cytologic examination and to analysis of lactate dehydrogenase (LDH), total protein, albumin and cholesterol. In addition, peritoneal fluid to serum ratio of LDH and total protein, as well as serum CA-125 were assayed. The biochemical parameters were compared between cases of ovarian cancer and cases of benign ovarian tumor, as well as between the different histological types and stages of ovarian cancer. RESULTS: All the examined parameters demonstrated a significant difference comparing patients with ovarian cancer and those with benign ovarian tumor (p<0.001). Yet, the greatest diagnostic accuracy was achieved by measuring peritoneal fluid LDH (86%) and cholesterol (93%). Moreover, significant differences in the level of assayed parameters were found when comparing different histological types and stages of ovarian cancer. In order to further corroborate the diagnostic performance, we combined the parameters of LDH and cholesterol with cytology, thus increasing the diagnostic accuracy to 96%. CONCLUSION: The association of peritoneal fluid LDH and cholesterol may represent a primary tool for the discrimination of patients with ovarian cancer (even borderline) from those with benign ovarian tumor, particularly in the presence of negative cytology.     

Intracystic evaluation of tumor markers in benign and malignant ovarian pathology

OBJECTIVE: To evaluate, in patients with benign and malignant ovarian cysts, serum samples and ovarian intracystic fluids for the presence of tumor markers such as CA 125, CA 15.3, tissue polypeptide antigen (TPA), CA 19.9 and the carcinoembryonic antigen (CEA). MATERIAL AND METHOD: We studied overall 64 patients with ovarian pathology. Sixteen patients were affected by functional cysts, 28 women by benign cystic tumors and 20 by cystoadenocarcinomas. RESULTS: Average serum levels of all but CA 15.3, TPA and CEA tumor markers of benign cystic ovarian tumors were higher than those of functional cysts. All but CA 19.9 mean intracystic fluid markers levels were more elevated in benign tumors than in functional cysts. In patients with malignant cystic tumors, all but CEA mean serum marker levels were higher than those of benign tumors; furthermore even all mean intracystic levels of markers were more elevated than those of benign tumors. CONCLUSION: This study confirmed the high positivity of tumor markers such as CA 125, CA 15.3, TPA, CA 19.9 and CEA in both the serum and intracystic fluid of patients with malignant epithelial ovarian tumors.     

4种肿瘤标志物对上皮性卵巢癌定性诊断价值的初步研究

目的：探讨多胺（ＰＡ）、ＣＡ１２５、ＣＡ１５．３和ＣＡ１９．９在定性诊断上皮性卵巢癌中的价值。方法：应用ＨＰ％Ｍ高效液相色谱仪和ＨＰ１０４０Ａ荧光检测器或酶联免疫吸附法测定上皮性卵巢癌４０例和卵巢良性肿瘤１８例血清中ＰＡ、ＣＡ１２５、ＣＡ１５．３和ＣＡ１９．９水平。结果：４种标志物中，ＰＡ诊断卵巢癌的敏感性、阳性预测率、阴性预测率和预测准确率最高，其次是ＣＡ１２５。结论：ＰＡ对人类恶性肿瘤缺乏特异性，但可作为鉴别卵巢良、恶性病变的有价值标志物。联合测定ＰＡ和ＣＡ１２５时，其敏感率为９４．９％。因此，联合测定ＰＡ和ＣＡ１２５可作为筛查卵巢良、恶性肿瘤的方法。     

The importance of serum insulin-like growth factor-I level determination in the follow-up of patients with epithelial ovarian cancer.

PURPOSE OF INVESTIGATION: The aim of our study was to assess whether serum levels of serum insulin-like growth factor-I (IGF-I) could be used for the follow-up of the patients with epithelial ovarian cancer and to identify whether it was superior to serum CA 125. METHODS: Our study group consisted of 28 patients diagnosed with epithelial ovarian cancer who had initial high serum CA 125 levels and have received chemotherapy following the operation. Preoperatively and before each chemotherapy administration, serum CA 125 and IGF-I levels were measured. RESULTS: The mean value of preoperative serum CA 125 was 364.0 +/- 152.9 U/ml. Serum CA 125 levels decreased with chemotherapy (Spearman rs= - 0.641, p=0.000). The mean preoperative serum IGF-I concentration was 58.04 +/- 52.7 ng/ml, and it showed a slight increase with chemotherapy. (Spearman rs=0.3 18, p=0.001). We observed that there was a weak-moderate negative correlation between the two markers, and when chemotherapy was administered serum CA 125 levels which were initially high started to decrease while serum IGF-I levels showed a mild increase (Spearman rs= - 0.350, p=0.000). CONCLUSION: The measurement of serum IGF-I does not provide any additional benefit in monitoring the response of the disease to chemotherapy.     

卵巢上皮性癌患者肿瘤组织和血清KLK8的表达及临床意义

目的:探讨激肽释放酶8(KLK8)在卵巢癌中的表达及其意义。方法:免疫组化法检测卵巢上皮性肿瘤组织中KLK8蛋白的表达水平,其中良性卵巢肿瘤20例、交界性卵巢肿瘤11例、卵巢癌62例,并测量其平均灰度值(A值);酶联免疫吸附(ELISA)双抗体夹心法检测血清KLK8浓度;分析卵巢癌组织中KLK8表达的A值与血清浓度值之间的相关性,比较血清KLK8、CA125检测用于卵巢癌诊断的敏感度及特异度。结果:(1)良性卵巢肿瘤、交界性卵巢肿瘤及卵巢癌中KLK8阳性表达率分别为25%(5/20)、27.3%(3/11)及66.1%(41/62),卵巢癌组阳性表达率明显高于前两组(P<0.05)。在不同临床病理特征间,差异亦有统计学意义(P<0.05);(2)血清KLK8浓度分别为4.26±0.29、5.26±0.46、6.59±0.15μg/L,差异有统计学意义(P<0.01);(3)卵巢癌组织KLK8表达的A值为156.4±14.7,与血清浓度值呈显著正相关,Spearman等级相关系数为0.608(P<0.001);(4)KLK8用于卵巢癌诊断的敏感度61.3%,特异度77.4%,与CA125差异无统计学意义(P>0.05)。结论:卵巢癌组织及血清中KLK8蛋白表达升高,并参与卵巢上皮性癌的发生发展过程,血清KLK8检测可指导卵巢癌的早期诊断。     

上皮性卵巢癌转移模式相关分子初探

目的:筛选和比较不同临床分型(淋巴结转移型/腹膜转移型/混合型)的III期卵巢癌原发灶中的差异表达分子,为晚期卵巢癌的分子分型提供参考。方法:用Tumor Metastasis PCR Array检测淋巴结转移型与腹膜转移型肿瘤组织中肿瘤转移相关分子mRNA表达,Western blot、免疫组化法在肿瘤组织及石蜡包埋组织切片中进一步验证PCR array法筛选出的差异表达分子在蛋白水平的差异表达情况。结果:Tumor Metastasis PCR array筛选出差异表达分子共14个,挑选文献报道的与其它肿瘤淋巴结转移和(或)腹膜转移相关的SMAD4、CCL7、CDKN2A及SERPINE1 4个分子。Western blot结果示,p16(CDKN2A)、CCL7及PAI-1(SERPINE1)在淋巴结转移型原发灶组织中的蛋白表达水平均显著高于腹膜转移型组织。免疫组化结果显示,72例III期上皮性卵巢癌的石蜡包埋组织中,PAI-1蛋白表达水平在淋巴结转移组、腹膜转移组及混合组之间有显著差异,平均评分分别为10.7、7.28及8.13分(P=0.036)。结论:PAI-1表达水平在不同转移模式的IIIc期卵巢癌中存在显著差异,在淋巴结转移型组织中最高,其次为混合型,腹膜转移型最低,可考虑作为卵巢癌分型的潜在分子标记物。     

Tamoxifen in patients with advanced epithelial ovarian cancer

Tamoxifen was administered to 30 patients with persistent or recurrent epithelial ovarian cancer following initial plantinum-based chemotherapy. Two complete remissions (lasting 41 months and 12 months, respectively) were documented (6.6%), while 10 patients (33.3%) had stabilization of disease for a mean duration of 11.5 months. Tamoxifen was not associated with any significant toxicity and is a reasonable therapeutic option for patients with persistent or recurrent ovarian cancer, although it is only associated with modest activity. This paper reviews our experience with tamoxifen and summarizes the world literature.     

彩色多普勒超声鉴别良恶性卵巢肿瘤的研究

目的　探讨经腹部、阴道二维超声及彩色多普勒鉴别良、恶性卵巢肿瘤的特点及意义。方法　自2 0 0 0年 1月至 2 0 0 2年 1月 ,对 2 5 0例卵巢肿瘤进行二维超声及彩色多普勒检测 ,并对良恶性卵巢肿瘤的形态、包膜、腹水、周边、内部血流阻力指数及血清CA12 5进行比较。结果　良恶性卵巢肿瘤的形态、包膜差异有显著性(P <0 0 1)。 6 4 %的恶性肿瘤可测出腹水 ,而良性肿瘤腹水仅占 0 7%。两者周边血流差异无显著性 ( P >0 0 5 ) ,内部血流差异有显著性 (P <0 0 1) ;17例中晚期恶性卵巢肿瘤病人的血清CA12 5均增高。结论　超声形态学和彩色多普勒探查卵巢肿瘤的动脉血流阻力指数 ,辅助血清CA12 5测值 ,是鉴别良恶性卵巢肿瘤的有效方法