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.     

CA125 in ovarian cancer: European Group on Tumor Markers guidelines for clinical use

CA125 is currently the most widely used tumor marker for ovarian epithelial cancer. The aim of this article is to provide guidelines for the routine clinical use of CA125 in patients with ovarian cancer. Due to lack of sensitivity for stage I disease and lack of specificity, CA125 is of little value in the detection of early ovarian cancer. At present, therefore, CA125, either alone or in combination with other modalities, cannot be recommended for screening for ovarian cancer in asymptomatic women outside the context of a randomized controlled trial. Preoperative levels in postmenopausal women, however, may aid the differentiation of benign and malignant pelvic masses. Serial levels during chemotherapy for ovarian cancer are useful for assessing response to treatment. Although serial monitoring following initial chemotherapy can lead to the early detection of recurrent disease, the clinical value of this lead-time is unclear. CA125 is the ovarian cancer marker against which new markers for this malignancy should be judged.     

eIF-4E、OPN在上皮性卵巢癌患者血清中的表达及临床意义

目的:检测eIF-4E、OPN在上皮性卵巢癌患者血清中的表达,探讨eIF-4E、OPN作为肿瘤标志物,与CA125联合检测的临床意义。方法:采集卵巢上皮性癌46例,卵巢交界性上皮性肿瘤16例、卵巢良性上皮性肿瘤12例及健康妇女12例的血清标本,用双抗体夹心(ELISA)法检测血清标本中eIF-4E、OPN的浓度,血清CA125浓度用化学发光法检测。结果:卵巢恶性肿瘤组及交界性肿瘤组血清中eIF-4E、OPN、CA125的浓度明显高于卵巢良性肿瘤组及正常对照组。eIF-4E检测阳性率63.04%,OPN检测阳性率76.9%,CA125检测阳性率71.74%,eIF-4E和CA125联合检测阳性率93.48%,OPN和CA125联合检测阳性率89.13%,eIF-4E、OPN及CA125三者联合检测阳性率97.83%。Ⅲ、Ⅳ期卵巢癌患者血清中CA125、eIF-4E、OPN浓度明显高于Ⅰ、Ⅱ期。结论:eIF-4E、OPN可作为卵巢肿瘤标志物,用于卵巢癌早期诊断,与CA125联合检测有较高的临床应用价值。     

Placental alkaline phosphatase (PLAP)/PLAP-like alkaline phosphatase as tumour marker in relation to CA 125 and TPA for ovarian epithelial tumours

The significance of the PLAP (Placental alkaline phosphatase)/PLAP-like isozyme as tumour marker in relation to CA 125 and TPA for the monitoring of patients with malignant ovarian epithelial tumours was evaluated. Of all patients (n = 85), 40% had all three markers elevated. CA 125 being the most sensitive (60%), and the PLAP/PLAP-like isozyme and TPA both 40%. A tendency to certain tumour marker patterns of these three antigens in serum can be seen with regard to histopathology. Serous and anaplastic adenocarcinomas usually have all three markers moderately elevated, mucinous and mesonephric adenocarcinomas both have low incidences and low average levels of all three markers. Endometrioid and non-mucinous adenocarcinomas are often associated with high levels of the PLAP/PLAP-like isozyme and CA 125, while TPA shows moderate elevation. The PLAP/PLAP-like isozyme is positively correlated to tumour burden and the outcome of the disease. It may provide additional information on CA 125 in the monitoring of patients with ovarian cancer.     

The value of CA 125 determination in the serum of patients with ovarian cancer

The circulating ovarian cancer associated antigen CA 125 was determined in serum of 63 patients with ovarian malignancies by radioimmunometric solid phase assay using the monoclonal antibody OC 125 as catcher and tracer. The results of 41 patients with 43 active tumour situations were compared with the CA 125 serum levels of 27 patients without recurrence after therapy of ovarian cancer and 49 benign ovarian tumours. Significant differences exist between these three groups (p less than 0.001) with elevated values (greater than 35 U/ml) in 84 per cent in ovarian carcinoma, 22 per cent in benign tumours and nought per cent in woman without recurrence in follow-up. The pre-operative sensitivity in ovarian cancer is 93 per cent (in epithelial carcinoma 96 per cent) with a distinct dependence of the CA 125 serum levels on the stage of the disease (stage III and IV versus stage I and II; p less than 0.01). A positive correlation of CA 125 values to clinical status was found in 82 per cent in follow-up. Increasing values of CA 125 can detect the recurrence any months earlier than the clinical examination. Decreasing serum levels in chemotherapy don't reflect the objective tumour remission in every case. Because of elevated values in benign and inflammatory adnexal tumours and the relative low sensitivity in borderline cases (three of seven patients greater than 35 U/ml) the CA 125 assay seems not be suitable for a screening method. However it is a substantial amplification in control of therapeutic success and an early detection of recurrence of ovarian cancer disease.     

The clinical significance of pre-operative serum CA 125 in ovarian cancer

In a prospective study of 52 patients with ovarian malignancy followed up for 3-18 months the clinical significance of pre-operative serum CA 125 as a tumour marker was assessed. In 41 patients with epithelial ovarian cancer, the level of CA 125 correlated well with tumour load as indicated by FIGO stage. All epithelial histological types, including mucinous, released CA 125 although serous and undifferentiated tumours produced quantitatively more antigen. There was, however, no correlation between CA 125 concentration and histopathological grade, nor did CA 125 level appear to be of any prognostic value in epithelial ovarian cancer. Elevated CA 125 levels were also found in patients with sex cord/stromal tumours. Krukenberg tumours, an ovarian sarcoma and a serous carcinoma of low malignant potential.     

Combination assay of CA125, TPA, IAP, CEA, and ferritin in serum for ovarian cancer

The levels of CA125, TPA, IAP, CEA, and ferritin in the serum were measured simultaneously in 68 healthy nonpregnant females and 133 patients with various gynecological diseases, and were subjected to statistical discriminant analysis for the diagnosis of ovarian cancer. The usefulness and the limits for diagnosis of various gynecological diseases were investigated for each tumor marker. Also, the diagnostic usefulness of the stepwise discriminant analysis employing the values of these five tumor markers in the serum in cases of ovarian cancer was compared with that of CA125 measurements alone. Because the frequency of cases with an elevated serum CA125 level increased more specifically in the ovarian cancer group than those of other tumor makers in the serum, this parameter was considered to be more useful for the diagnosis of ovarian cancer than the levels of the other tumor markers. The frequencies of cases with the elevated serum CA125 levels, however, also increased in the groups of patients with endometriosis and at an early stage of normal pregnancy more than in the group of healthy nonpregnant females. In the ovarian cancer patients, the discriminant analysis employing the values of CA125 and four other tumor markers in sera was more useful for early diagnosis, differential diagnosis, early detection of recurrences, and the determination of complete remission after therapy than the measurement of the serum CA125 level alone.     

组织多肽抗原在卵巢癌诊断及监测中的应用

目的评价组织多肽抗原（ＴＰＡ）在卵巢癌诊断和监测中的临床价值。方法应用放射免疫方法测定了２４例正常妇女、２７例妇科良性疾患及６０例卵巢癌患者的血清ＴＰＡ及ＣＡ１２５值并进行比较分析。结果ＴＰＡ在卵巢上皮性癌患者中的异常检出率为８２％,ＣＡ１２５为７０％,二者总的异常检出率为９２％。在绝大多数正常妇女和卵巢良性肿瘤患者中,ＣＡ１２５和ＴＰＡ在正常范围。作为卵巢癌相关标志物,ＴＰＡ与ＣＡ１２５具有相似敏感性。１９例动态观察结果显示,ＴＰＡ和ＣＡ１２５二者与病情转归是一致的。结论ＴＰＡ和ＣＡ１２５联合应用对卵巢癌的鉴别诊断及提高总的异常检出率具有价值。     

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.     

Comparison of cathepsin-B-like activity and CA 125 assays use in ovarian cancer diagnosis

BACKGROUND: Determination of serum cathepsin B-like activity was used as a diagnostic marker of ovarian cancer. The aim of this study was to compare its diagnostic utility with CA 125 assay. METHODS: In 50 patients with epithelial ovarian cancer and 20 with ovarian cyst cathepsin B-like activity by fluorimety and CA 125 concentration by luminiscence immunoassay, were determined. The obtained results were compared by two cut-off values computed from the data obtained in healthy controls and ovarian cysts (cathepsin B: 11 and 108 mU/ml; CA 125: 35 and 135 U/ml), respectively. RESULTS: In differential diagnosis between ovarian carcinomas and ovarian cysts cathepsin B shows similar specificity (95%) as CA 125 but higher sensitivity (63.5% vs 50%). Both cathepsin B and CA 125 are good predictors of tumour response and recurrence CONCLUSIONS: Adding CA 125 determination to cathepsin B-like activity in the laboratory diagnostics of ovarian cancer increased the sensitivity and positive predictive values as compared to the use of cathepsin B alone.     

Serum CA 125 in epithelial ovarian cancer. A longitudinal study

Plasma levels of CA 125 were determined in 113 patients with ovarian cancer of epithelial origin. Of these, 69 patients had CA 125 measured before the first laparotomy and 84.6% of them had a CA 125 level greater than 35 U/ml. In 87 of the 113 patients whose tumour was producing CA 125, a good correlation was observed between the CA 125 levels and the clinical follow-up: 95.7% of the patients in remission had levels less than 35 U/ml, whereas all the patients with no change or with a progressive disease had levels greater than 35 U/ml. Furthermore in recurrent disease the levels of CA 125 were also increased (greater than 35 U/ml) in 92.3% of the patients. Thus, CA 125 measurements at regular intervals are of great clinical value in following the evolution of a tumour or the success of a therapy, but unfortunately do not allow detection of an ovarian tumour at an early stage.     

血清Cyfra21-1诊断卵巢恶性肿瘤的研究

目的 :研究细胞角蛋白片段抗原 2 1- 1(Cyfra2 1 1)对卵巢恶性肿瘤诊断及疗效判断的临床意义。方法 :应用免疫放射分析法 (IRMA)测定 10 2例卵巢肿瘤患者及 2 0例正常妇女血清中Cyfra2 1 1和CA12 5的水平 ,并对 12例Cyfra2 1 1阳性的恶性组患者于术后 1周开始 ,每月 1次 ,进行 4个月血清水平的动态观察。结果 :Cyfra2 1 1诊断卵巢恶性肿瘤的敏感性、特异性、准确性分别为 80 0 %、10 0 0 %、89 0 % ,CA12 5分别为 85 0 %、6 2 .0 %、76 .0 % ,Cyfra2 1 1诊断的特异性和准确性明显高于CA12 5(P <0 .0 1,P <0 .0 5 )。上皮性癌和转移性腺癌患者血清Cyfra2 1 1含量显著高于其他组织类型 (P <0 .0 5 ) ,分化程度不同的肿瘤血清Cyfra2 1 1水平差异有非常显著性 (P <0 .0 1) ,血清Cyfra2 1 1值与临床分期显著相关 (P <0 .0 0 1)。Cyfra2 1 1浓度在术后 1周明显下降 ,术后 1个月内恢复至正常范围。下降不明显或下降后再升高者 ,提示病情进展或复发。结论 :血清Cyfra2 1 1测定对卵巢恶性肿瘤患者的早期诊断、病情监测和疗效评估有重要的临床应用价值。     

Serum CA 125 in epithelial ovarian cancer. A longitudinal study

Summary. Plasma levels of CA 125 were determined in 113 patients with ovarian cancer of epithelial origin. Of these, 69 patients had CA 125 measured before the first laparotomy and 84.6% of them had a CA 125 level >35 U/ml. In 87 of the 113 patients whose tumour was producing CA 125, a good correlation was observed between the CA 125 levels and the clinical follow-up: 95.7% of the patients in remission had levels < 35 U/ml, whereas all the patients with no change or with a progressive disease had levels >35 U/ml. Furthermore in recurrent disease the levels of CA 125 were also increased (>35 U/ml) in 92.3% of the patients. Thus, CA 125 measurements at regular intervals are of great clinical value in following the evolution of a tumour or the success of a therapy, but unfortunately do not allow detection of an ovarian tumour at an early stage.     

LPA、CA125与经阴道彩色多普勒超声联合诊断卵巢上皮癌的临床价值

目的:探讨血浆溶血磷脂酸(LPA)在卵巢上皮癌患者血浆中的表达水平,及其与血清CA125和经阴道彩色多普勒超声(TV-CDUS)联合应用诊断卵巢上皮癌的临床价值。方法:术前检测卵巢上皮癌48例,卵巢良性肿瘤30例的LPA、CA125,以20例健康者作为对照,卵巢肿瘤患者同时经阴道超声评分和TV-CDUS检查。结果:卵巢癌患者LPA水平明显高于卵巢良性肿瘤组和健康对照组,差异有统计学意义(P0.05),LPA水平在良性肿瘤组与健康对照组之间无显著差异(P0.05)。单独应用LPA、CA125、TV-CDUS检测诊断卵巢癌的敏感性和特异性分别为87.5%、79.16%、81.25%和80%、70%、86%,各组间敏感性和特异性比较,无显著差异(P0.05)。LPA、CA125、TV-CDUS 3项联合检测诊断卵巢癌的敏感性和特异性为95.80%和94%,与单独应用CA125检测特异性比较,差异有统计学意义(P0.05)。LPA诊断卵巢癌的敏感性和特异性与卵巢癌分期和病理类型无关(P0.05),CA125诊断卵巢癌的敏感性和特异性与卵巢癌的分期和病理类型有关(P0.05)。结论:卵巢上皮癌患者血浆LPA水平明显升高,有望成为卵巢上皮癌诊断的敏感指标,联合检测血浆LPA、血清CA125与TV-CDUS有助于术前卵巢癌的诊断。     

Monitoring human ovarian carcinoma with a combination of CA 125, CA 19-9, and carcinoembryonic antigen

CA 125 and CA 19-9 are antigenic determinants associated with human epithelial ovarian carcinomas. Murine monoclonal antibodies have been raised against these determinants, and immunoradiometric assays have been developed to monitor antigen levels in the serum of cancer patients. This study was undertaken to determine whether concomitant measurement of CA 125, CA 19-9, and carcinoembryonic antigen would provide a more precise correlation with tumor progression or regression than could be obtained with any single assay. Among 105 patients with surgically demonstrable epithelial ovarian carcinoma, serum CA 125 levels were elevated (greater than 35 U/ml) in 83%, CA 19-9, levels (greater than 37 U/ml) in 17%, and carcinoembryonic antigen levels (greater than or equal to 2.5 ng/ml) in 37%. Within individual samples, no correlation was found among values for the three markers, but patients with elevated CA 19-9 levels also had increased levels of CA 125. At least one of the three markers was elevated in 90% of the subjects. When 41 patients were monitored serially over 2 to 60 months, alterations in CA 125 levels correlated with disease progression or regression in 94% of instances, whereas alterations in CA 19-9 levels correlated in 33% and alterations in carcinoembryonic antigen levels in 25% of instances. Concomitant measurement of CA 125, CA 19-9, and carcinoembryonic antigen did not prove superior to measurement of CA 125 alone in the monitoring of patients with epithelial ovarian carcinoma.     

Ovarian Thecoma Associated with a Large Quantity of Ascites and Elevated Serum CA 125 and CA 15-3

Background: Elevation of tumour marker CA (cancer antigen) 125 associated with Meigs’ or atypical Meigs’ syndrome is widely recognized. Other tumour markers are available to assist in distinguishing between benign and malignant ovarian masses in the preoperative diagnosis.Case presentation: A 57-year-old woman presented with a suspicious pelvic mass and abundant ascites. Preoperative tumour markers CA 125 and CA 15-3 were elevated at 1750 U/mL and 60 U/mL, respectively. The woman underwent surgery, and 9 L of straw-coloured ascites were drained along with a solid-cystic ovarian mass. The final pathology disclosed an ovarian thecoma. Six months later, both tumour markers were normal.Conclusion: This first report of 2 elevated tumour markers associated with atypical Meigs’ syndrome cautions us not to rely on tumour markers to differentiate benign from malignant masses.     

应用多项肿瘤标记物检测卵巢恶性肿瘤的研究

目的为了提高卵巢恶性肿瘤诊断的特异性及敏感性,加强术后患者的病情追踪。我们应用５项肿瘤标记物ＳＡ,ＬＳＡ,ＣＡ１２５,ＣＰ２,６Ｂ１１Ａｂ２进行临床观察。方法对６７例卵巢恶性肿瘤及３３例卵巢良性肿瘤患者进行血清检测,以３８例正常妇女进行对照。结果单纯应用ＣＡ１２５诊断卵巢恶性肿瘤的敏感性及特异性分别为８３６％及８５９％,而５项肿瘤标记物中以任意３项及３项以上阳性为标记物诊断阳性时,检测卵巢恶性肿瘤的敏感性及特异性分别为８６６％及９４４％。临床Ⅰ、Ⅱ期患者的５项肿瘤标记物联合检测的特异性及敏感性,较ＣＡ１２５单项检测有明显提高。结论５项肿瘤标记物联合检测,对提高卵巢恶性肿瘤诊断的准确性及术后监测有一定意义     

The present and the future of tumor markers]

Recently, it has been revealed that cancer cells produce many substances that are hardly detectable in healthy people. Some of these substances are found in the bloodstream and are clinically used as serum tumor markers. Breakdown products of these serum tumor markers are discharged into the urine; and, therefore, urine can also be a good source of samples for cancer diagnosis. In addition, as other substances remain on or in the cancer cells, we may be able to develop new assay systems using cancer cells as the sample. 1. Serum tumor markers: Many of the recently developed tumor markers are sugar antigens, and are clinically useful for the diagnosis of ovarian cancers. These sugar antigens can be classified into three major categories; core protein-related antigens (CP-RA), core of sugar chain-related antigens (CSC-RA) and periphery of sugar chain-related antigens (PSC-RA). CA125, CA602, and CA130 belong to CP-RA; CA602, CA72-4, and sialyl Tn to CSC-RA; and CA19-9 and sialyl Lewis X (SLX), to PSC-RA. The positive rates of CP-RA in the sera of patients with ovarian epithelial cancers are usually very high except in the case of mucinous cystadenocarcinomas. Meanwhile, those of CSC-RA are higher than those of CP-RA in the sera of mucinous cystadenocarcinoma patients, and the false-positive rate of CSC-RA is lower than that of CP-RA in benign ovarian tumors. The diagnostic efficiency of PSC-RA is inferior to that of CA-RA and CSC-RA. Multi-variate analysis has revealed that the combination assay of these two groups of markers is the most effective among the sugar antigen assays for the diagnosis of epithelial ovarian cancers. 2. Urine tumor markers: beta-core fragment (beta-CF), a fragment of the hCG beta-subunit missing its carboxy-terminal peptide, is often detected in the urine of gynecological malignancies, indicating that urine can be a good sample source for cancer detection.(ABSTRACT TRUNCATED AT 250 WORDS)     

Preoperative plasma osteopontin level as a biomarker complementary to carbohydrate antigen 125 in predicting ovarian cancer

AIM: New biomarkers other than carbohydrate antigen (CA) 125 are needed for the detection of ovarian cancer. Osteopontin (OPN) is one of the candidates identified by high-throughput complementary DNA microarray techniques. We evaluated the preoperative plasma OPN level as a diagnostic biomarker for ovarian cancer in comparison with CA125. METHODS: Preoperative plasma OPN and CA125 levels were measured and compared in 32 patients with ovarian cancer, 34 patients with benign ovarian tumor, 30 patients with other gynecologic cancers and 31 healthy women. Preoperative plasma OPN levels were also assessed according to tumor stage, the volume of ascites and histological types. The sensitivity and specificity for predicting ovarian cancer was compared between OPN and CA125. RESULTS: Preoperative plasma OPN levels were significantly higher in patients with ovarian cancer than in those with benign ovarian tumor, in other gynecologic patients or in healthy women. Stage IV ovarian cancer patients and ovarian cancer patients with ascites had higher plasma OPN levels than those without ascites and in a lower stage. There was no relation between OPN and the histological type. The sensitivity of preoperative plasma OPN in detecting ovarian cancer was 81.3% and almost reached that of CA125. The specificity was moderate. Sensitivity increased to 93.8% with the combination of CA125, compared to 84.4% with CA125 alone. CONCLUSION: Preoperative OPN is a useful biomarker for predicting ovarian cancer. It is especially useful when used complementary to CA125. Larger studies of patients with ovarian cancer showing a low CA125 level or in early stages of ovarian cancer are needed.     

Multiple Immunoreactive Inhibin Proteins in Serum from Postmenopausal Women with Epithelial Ovarian Cancer

Inhibin is an ovarian protein previously shown, using a nonspecific assay, to be elevated in serum of women with ovarian cancer. However, inhibin is secreted in multiple biochemical forms, including dimeric inhibin A and B and α inhibin precursors (pro-αC), each of which can now be specifically measured. We have examined the secretion of inhibin B and pro-αC inhibin in serum from women with epithelial ovarian cancer (EOC) for the first time, and have compared these analytes to inhibin A and total inhibin (inhibin A + B + pro-αC) as potential serum markers for EOC in postmenopausal women. Of all the immunoreactive inhibin proteins studied, the best serum marker was pro-αC, with 22% of women with EOC having levels that exceeded the range of values in women without EOC. Since CA 125 and pro-αC levels were not significantly correlated, combination of these markers resulted in 87% of EOC cases having elevated preoperative serum levels, a 9% increase over CA 125 alone. These data suggest that α inhibin secretion, especially pro-αC, may be useful in addition to CA 125 as a serum marker for EOC in postmenopausal women.