Cirrhotic ascites, ovarian carcinoma, and CA-125

We describe two postmenopausal women with ascites and elevated CA-125 level, a serologic marker used to detect ovarian cancer. Both patients had unrecognized liver disease but underwent surgical exploration for suspected ovarian disease, which subsequently revealed benign pelvic organs. Elevated serum CA-125 levels have been reported in many patients with ascites due to liver disease and cirrhosis. Thus, the presence of both ascites and an elevated CA-125 level mandates a thorough elevation for liver disease as well as for a possibility of ovarian carcinoma. These cases outline the common finding and provide insight into the management of patients with ascites and elevated CA-125 values.     

The management of anxiety and knowledge of serum CA-125 after an ovarian cancer diagnosis

This article describes the relationship among anxiety, distress, and serum CA-125 levels in women with ovarian cancer. Women's anxiety about monitoring their CA-125 levels during chemotherapy also is discussed. Data from a randomized trial including self-reported anxiety and emotional distress of women following surgery after a primary diagnosis of ovarian cancer, their recorded serum CA-125 levels, and knowledge about their CA-125 levels were analyzed. In the sample, 26 of 30 women had serum CA-125 levels above the normal range. At baseline, the sample had an elevated mean anxiety score and an elevated distress score. A moderate association was found between a high serum CA-125 level and a high anxiety score at baseline, but the finding was not statistically significant. A negative nonsignificant relationship was found between a high serum CA-125 level and distress at baseline. The qualitative analysis revealed two themes: anxiety and lack of knowledge of serum CA-125. Oncology nurses and nurse practitioners caring for these women should provide essential information and strategies that can help guide women with ovarian cancer through the journey of their disease.     

4种肿瘤标志物的检测对卵巢癌的诊断价值

目的 探讨肿癌胚抗原(CEA)、糖类抗原199(CA-199)、糖类抗原125(CA-125)和糖类抗原153(CA-153)等4种肿瘤标志物的检测对卵巢癌的诊断价值.方法 采用化学发光法检测49例卵巢癌患者、48例卵巢良性病变患者和40例健康体检者的口述4种肿瘤标志物,并探讨联合检测对诊断卵巢癌的临床价值.结果 49例卵巢癌患者血清CEA、CA-199、CA-125和CA-153阳性率明显高于卵巢良性病变组及健康对照组(均P<0.05),4项联合检测敏感性明显高于单项检测.结论 单项检测血清CEA、CA-199、CA-125和CA-153对卵巢癌的诊断有一定的临床价值,联合检测这4种标志物更具有临床意义.     

Pronounced increases in the concentration of an ovarian tumor marker, CA-125, in serum of a healthy subject during menstruation

CA-125 is a glycoprotein associated with various ovarian tumors. A commercial radioimmunoassay involving a monoclonal antibody is available for it. In our laboratory, a normal-value study was conducted as part of a routine evaluation of this assay. One healthy subject had a serum CA-125 concentration greater than 300 kU/L, more than eightfold the upper limit of normal (35 kU/L). This increase, which coincided with the onset of the menstrual period, subsided to within the normal range by the end of the menstrual cycle. The half-life of CA-125, calculated from this decrease, was 6.4 days. Similar observations were made in the same subject over several menstrual cycles. Results of clinical and ultrasound examinations of the subject for ovarian tumors were negative. No clinical evidence of malignancy was present eight months after the initial discovery of an increased CA-125. None of the other 39 healthy subjects had a CA-125 value greater than 51 kU/L. Five of these subjects had CA-125 determined several times during their menstrual cycles; none exhibited pronounced variations in CA-125 concentrations. Evidently CA-125 can be extremely increased in a healthy woman, and possible effects of the menstrual period on serum CA-125 concentrations should be considered in pre-menopausal patients.     

非小细胞肺癌GP方案化疗前后肿瘤标志物变化临床意义分析

目的评估非小细胞肺癌(NSCLC)化疗前后血清癌胚抗原(CEA)、糖类抗原125(CA-125)、血清细胞角质素片段抗原21-1(CYFRA 21-1)变化的临床意义。方法 40例NSCLC患者行吉西他滨+顺铂(GP方案)化疗,根据疗效分为稳定组(26例)和进展组(14例)。在化疗前后,全部清晨空腹采集血清样本,冷冻保存。用电化学发光免疫测定法检测血清CEA、CA-125、CYFRA 21-1的含量水平。结果稳定组化疗后NSCLC患者血清中CEA、CA-125、CYFRA 21-1水平明显低于治疗前(P<0.05)。而进展组化疗前后此3项指标变化无统计学意义(P>0.05)。结论血清CEA、CA-125、CYFRA 21-1联合检测可作为NSCLC化疗疗效的评价指标。     

Serum levels of CA-50, CA-19.9, CA-125, neuron specific enolase and carcinoembryonic antigen in lung cancer and benign diseases of the lung

The serum levels of five markers (CA-50, CA-19.9, CA-125, Enolase (NSE) carcinoembryonic antigen (CEA) were studied in 96 lung cancer patients and in 60 patients with benign diseases of the lung: sensitivity was 0.44, 0.41, 0.54, 0.23 and 0.38 respectively; specificity was 0.67, 0.87, 0.47, 0.93 and 0.97 respectively. Serum levels of CA-125 over 20 U/ml were found in 74% of patients with acute pneumonia. A good parallel existed between the clinical evolution of lung cancer and the variations in the serum level of CA-50, CA-19.9 and NSE. Although the pretreatment result was elevated, successive assays of the marker allowed the clinical evolution to be followed. Conflicting results were found with CA-125 and to a lesser extent with CEA. A close correlation existed between the serum levels CA-50 and CA-19.9 in the 2 groups of patients. In the absence of a specific marker for lung cancer, complementary information can be provided by means of a simultaneous determination of CEA, NSE, CA-19.9--or CA-50--and CA-125.     

血清FS及CA125用于卵巢癌诊断的比较研究

目的比较卵泡抑素(Follistatin,FS)及CA125在卵巢癌患者血清中的水平变化及其临床意义。方法分别采用ELISA法和电化学发光法检测卵巢癌、卵巢囊肿患者及健康对照者血清FS及CA125水平,ROC曲线分析二者用于卵巢癌诊断的准确性。结果卵巢癌患者血清FS水平明显高于健康对照组,统计学比较差异显著,P<0.01。以健康对照组血清FS及CA125水平的95%可信区间判断卵巢癌患者血清FS水平,显示血清FS用于卵巢癌诊断时灵敏度为53.3%,特异性为97%;血清CA125的诊断灵敏度为77.8%,特异性为84%;血清FS用于卵巢癌诊断时ROC曲线下面积为0.902,略大于CA125的ROC曲线下面积(0.886)。结论卵巢癌患者血清FS水平升高,与血清CA125水平具有相关性,其用于卵巢癌诊断时准确性与CA125相近,特异性优于CA125。FS是一个很有应用前景的卵巢癌血清诊断标记物,与CA125联合应用有助于降低卵巢癌的误诊率。     

Follow-up of small,postmenopausal ovarian cysts using vaginal ultrasound and CA-125 antigen

To determine the natural history of small, simple ovarian cysts in post-menopausal women, 51 postmenopausal patients with small (<5 cm), smooth, aseptate, hypoechogenic ovarian cysts, without ascites, were followed by vaginal ultrasound examinations every 3 months for an average period of 2.5 years. In 34, CA-125 antigen was measured and found to be within normal limits. None of the cysts showed changes in texture, nor did ascites appear. The CA-125 antigen serum levels remained low. The mean size of the cysts decreased with time. There was no statistically significant correlation between the initial size of the cyst, its tendency to grow or shrink, and the absolute CA-125 serum level. Our findings support the option of a conservative follow-up by repeated ultrasonic and CA-125 antigen examinations of small, simple cysts in postmenopausal women. © 1996 John Wiley & Sons, Inc.     

Evidence for interaction of human anti-idiotypic antibodies with CA 125 determination in a patient after radioimmunodetection

Very high concentrations of CA 125 have been found in some ovarian cancer patients after repeated radioimmunodetection with anti-CA 125 antibodies [OC125-F(ab')2]. In one patient we measured a CA 125 concentration of 135,000 kilo-arb. units/L, using an enzyme immunoassay involving OC125 antibodies. With an immunoradiometric assay involving use of two new anti-CA 125 antibodies (B43.13 and B27.1), the CA 125 concentration was 34 kilo-arb. units/L, indicating a discrepancy. The component responsible for the high result in the enzyme immunoassay could be purified by immunoaffinity chromatography on Protein A-Sepharose. Furthermore this component bound to anti-human IgG-Sepharose in the same manner as did the serum IgG fraction. Adsorption of human anti-mouse antibodies present in the serum did not decrease the CA-125-like material. Binding of whole OC125 antibodies to the purified CA-125-like material was inhibited completely in the presence of CA 125 antigen. We infer that the false-positive CA 125 activity is ascribable to a human IgG directed against an idiotope of the OC125 antibody, which was induced by repeated application of OC125 antibodies. To avoid falsely positive results in patients receiving OC125 antibodies, CA 125 should be measured by an assay in which other antibodies are used.     

联合检测TPS和CA125在卵巢癌患者诊疗中的意义

【目的】探讨血清TPS和CA125与卵巢癌的关系,为卵巢癌的临床诊断、病情监测提供新方法。【方法】用ELISA法分别检测卵巢良性肿瘤和卵巢癌患者化疗前后血清TPS和CA125水平。【结果】卵巢癌患者血清TPS和CA125水平均较良性肿瘤患者高,差异有显著性(P<0. 01)。血清TPS和CA125诊断卵巢癌的敏感度和特异度无差别。卵巢癌患者2个疗程化疗后血清TPS和CA125水平显著下降(P<0. 01 )。【结论】血清TPS和CA125均可作为卵巢癌诊断、病情监测的临床指标,二者联合检测可提高其临床应用价值。     

Enzyme-linked immunosorbent assay of CA-125 in serum of patients with endometriosis: efficacy in diagnosis

We used an enzyme-linked immunosorbent assay to quantify CA-125, a cancer antigen, in serum of patients with endometriosis. Concentrations of CA-125 in 103 patients with untreated endometriosis significantly (P less than 0.005) exceeded those for 31 controls with no evidence of disease: 9.1 (SD 12.3) vs 2.2 (SD 3.2) arb. units/mL. Values for patients with treated endometriosis were lower (2.3, SD 2.6, arb. units/mL, n = 9) than those for patients with untreated endometriosis. The mean concentrations of CA-125 in different stages of untreated endometriosis were 4.8 (SD 4.5), 7.1 (SD 9.9), 9.8 (SD 13.2), and 10.8 (SD 13.0) arb. units/mL for Stages I, II, III, and IV, respectively. The differences between controls and each stage were statistically significant (for all stages: P less than 0.05). We also assayed serum sampled from controls and patients with untreated endometriosis during menstruation (Group A) and during nonmenstruation (Group B). The efficacy of the present assay for concentrations of CA-125 in serum of patients with endometriosis was greater for Group B than for Group A. Evidently, determination of CA-125 in serum by the present assay may assist in such diagnosis.     

Distribution of radiolabelled anti-CA125 monoclonal antibody OC125-F(ab′)2-fragment following resection guided by antibodies (REGAJ) in ovarian cancer patients

Ovarian cancer is a highly malignant tumor of mainly postmenopausal women. The long-term prognosis of this malignancy is largely determined by micrometastasis present at the time of second-look surgery. In general, patients face a poor outcome. New radio-immunoscintigraphic methods to target tumor tissue specifically via antigen-antibody binding were developed. However, few studies so far investigated the pattern of in vivo distribution of radiolabelled mAbs and/or the specificity of antigen-antibody interaction. In this study we examined the immunological interaction and distribution of ¹³¹ I-OC125-F(ab′)₂-fragment, an anti-CA-125 mAb, in patients with CA-125 positive ovarian malignancies. Sixteen patients with primarily CA-125 positive gynecological tumors underwent REGAJ surgery. Biopsies of tumor tissue and not tumor infiltrated tissue, serum, and ascites were sampled during or prior to REGAJ surgery, respectively. After preparation of tissue cytosols, samples were assessed for CA-125 and radioactive uptake. By radiochromatography immunological analysis for presence of the target antigen CA-125, the mAb ¹³¹I-OC125-F(9ab′)2-fragment, and immune complexes was performed on different specimen. CA-125 concentrations were higher in serum samples, ascites, and malignant tissue biopsies of malignoma patients compared to those without signs of malignant disease. CA-125 was higher in the tissue cytosol than in the cell membrane fraction. Gel filtration revealed CA-125 with moieties of 75,000 to < 600,000 d. Accumulation of radioactivity was more frequently associated with the presence of unbound ¹³¹I-OC125-F(ab′)2-fragment or high molecular weight immune complexes. Radioactive uptake, however, was not confined to tissue of high CA-125 expression. Moreover, both immune complex as well as ¹³¹I-OC125-F(ab′)2-fragment could be isolated from cytosols of tissue not infiltrated by tumor cells as well. Our study demonstrates that the majority of CA-125 is located intracellularly and thus inaccessible to ¹³¹I-OC125-F(ab′)2-fragment per se. The uptake of ¹³¹I-OC125-F(ab′)2-fragment into the cytosol of tumor-free and malignant tissue samples prompts us to speculate that certain mechanisms for antigen-specific and nonspecific cellular trafficking of mAbs do exist. We present a model to explain our observations. J. Clin. Lab. Anal. 11:94–103. © 1997 Wiley-Liss, Inc.     

CA125及其半衰期监测进展期卵巢癌疗效和预后的意义

目的 :研究CA12 5及其半衰期监测进展期卵巢癌疗效及预后的应用价值。方法 :采用化学发光法测定 45例Ⅲ、Ⅳ期原发卵巢癌患者血浆CA12 5水平并计算CA12 5半衰期。结果 :45例患者治疗前血浆CA12 5水平均高于正常 ;采用单因素生存率时序检验 (Logranktest)分析表明 ,第 3次化疗后CA12 5水平、CA12 5半衰期及手术后残留灶大小、FIGO分期对预后有影响 (P值分别为 0 0 0 10、0 0 0 0 0、0 0 0 0 2、0 0 3 85 ) ;运用Cox风险回归模型进行多因素分析表明 :CA12 5半衰期对进展期卵巢癌患者有独立的预后价值 (χ2 =6 2 73 4,P =0 0 12 3 )。结论 :化疗早期CA12 5水平及其半衰期对进展期卵巢癌患者的预后评定有价值 ,检测该指标可及时发现耐药或复发 ,可及时给予相应的治疗措施。     

High CA-125 values in miliary tuberculosis and ascites

High levels of CA-125, the specific tumour marker for epithelial ovarian cancers are also found in inflammatory diseases of the pelvis. This case report of a 28 year-old woman with pathological CA-125 levels demonstrates the association between this finding and ascites caused by miliary tuberculosis. Tuberculostatic chemotherapy led to normalisation of the CA-125 levels within 8 weeks.     

Clinical potential of proteomics in the diagnosis of ovarian cancer

The need for specific and sensitive markers of ovarian cancer is critical. Finding a sensitive and specific test for its detection has an important public health impact. Currently, there are no effective screening options available for patients with ovarian cancer. CA-125, the most widely used biomarker for ovarian cancer, does not have a high positive predictive value and it is only effective when used in combination with other diagnostic tests. However, pathologic changes taking place within the ovary may be reflected in biomarker patterns in the serum. Combination of mass spectra generated by new proteomic technologies, such as surface-enhanced laser desorption ionization time-of-flight (SELDI-TOF) and artificial-intelligence-based informatic algorithms, have been used to discover a small set of key protein values and discriminate normal from ovarian cancer patients. Serum proteomic pattern analysis might be applied ultimately in medical screening clinics, as a supplement to the diagnostic work-up and evaluation.     

Prediction of 5-year survival in advanced-stage ovarian cancer patients based on computed tomography peritoneal carcinomatosis index

Objective

To evaluate whether the quantification of peritoneal metastases in advanced-stage ovarian cancer patients using the peritoneal carcinomatosis index, detected by CT (CT-PCI), correlates with the serum levels of tumor marker CA-125 and 5-year survival.

Methods

The CT-PCI was determined in 82 patients with stage III or stage IV ovarian cancer using the Sugarbaker classification prior to cytoreductive surgery. Linear regression analysis was used to correlate CT-PCI and CA-125 levels. Correlation of presurgical CT-PCI, optimal surgical cytoreduction, and 5-year survival was established using binary logistic regression analysis. A score for prediction of 5-year survival probability was established using multivariate backwards binary logistic regression.

Results

Presurgical CT-PCI correlates significantly with presurgical CA-125 serum levels (r = 0.487, P < 0.001). Multivariate binary logistic regression suggested significantly improved 5-year survival with lower CT-PCI and lower ECOG performance scores.

Conclusion

CT-PCI allows quantification of peritoneal disease in advanced-stage ovarian cancer patients, similar to CA-125. CT-PCI in combination with ECOG performance has the potential to help evaluate the 5-year survival probability.

     

Screening for ovarian cancer

Whilst the majority of patients with ovarian cancer present with advanced stage disease and have a poor prognosis, the outlook for women with stage I disease is relatively good. An effective screening test for early stage ovarian cancer may therefore result in a significant improvement in ovarian cancer statistics. Extremely high specificity is an essential requirement of any potential screening test in view of the need for surgical investigation of women with a positive test result. No single test has yet demonstrated sufficient specificity when used alone to screen apparently healthy postmenopausal women. A multimodal approach incorporating serum CA-125 measurement, pelvic examination and real time ultrasonography has achieved high levels of specificity. The sensitivity of this screening programme for early stage ovarian cancer is currently under investigation.     

Diagnostic usefulness of carbohydrate antigen-125 in cancerous and noncancerous peritoneal effusions

Carbohydrate antigen-125 (CA-125) is a tumor marker that has been used for differential diagnosis of peritoneal malignancies. The aim of the present study was to evaluate the diagnostic usefulness of simultaneous quantification of CA-125 in peritoneal fluid and serum for abdominal cancer cases and noncancer diseases. Noncancer disease group included cirrhotic patients (n=28) and spontaneous bacterial peritonitis (SBP) patients (n=11). Abdominal cancer group was composed of histologically diagnosed various malignancies (n=10), such as gastric cancer. CA-125 levels were quantified by chemiluminescent enzyme immuno-assay. Diagnostic usefulness tests and receiver operating characteristics (ROC) curve analysis were performed for the levels of peritoneal fluid CA-125 (pCA-125) and serum CA-125 (sCA-125), and the ratio of pCA-125 to sCA-125 (p/sCA-125). The sCA-125 levels were significantly higher in noncancer patients than those in the cancer patients, while the pCA-125 levels showed no significant difference between the two groups. Notably, the p/sCA-125 ratio was significantly lower in the noncancer patients than that in the cancer patients. Area under the ROC curve was 0.267 for sCA-125, 0.542 for pCA-125 and 0.831 for p/sCA-125. The accepted cutoff values were the combination of values that gave the greatest diagnostic sensitivity plus specificity. Either sCA-125 or pCA-125 value gave lower diagnostic accuracy, whereas p/sCA-125 value demonstrated a significantly higher diagnostic accuracy (sensitivity-specificity pairs: 0.40-0.33 for sCA-125, 0.60-0.54 for pCA-125, and 0.80-0.72 for p/sCA-125, respectively). Hence, determination of p/sCA-125 improves the biochemical discrimination of abdominal cancerous cases from noncancerous diseases.     

CA-125 concentrations in malignant and nonmalignant disease

CA-125 is a high-molecular-mass glycoprotein expressed on the cell surface of some derivatives of embryonic coelomic epithelium. This tumor-associated antigen widely used to monitor ovarian carcinomas has been suggested as a promising noninvasive test that could differentiate benign from malignant conditions. Based on results of various studies, CA-125 measurement appears to be very useful in monitoring the response to therapy of ovarian carcinoma and for detecting tumor recurrence as exemplified in Case 1. However, because of the high frequency of false-positive results associated with many benign conditions, CA-125 is of little value as a screening test for ovarian carcinoma. A brief list of the most common benign conditions associated with CA-125 increase includes menstruation, pregnancy, benign pelvic tumors, pelvic inflammatory diseases, ovarian hyperstimulation syndrome, peritonitis, and many diseases leading to pleural effusion or ascites. According to several studies, a marked increase in CA-125 of greater than 1000 units/mL, as seen in Case 2, and even up to 5000 units/mL, could be seen in some benign conditions. This finding further limits the value of CA-125 as a potential noninvasive procedure to differentiate benign from malignant diseases. Although values up to 10,000 units/mL are occasionally seen in patients with ovarian carcinoma, we are reluctant to state that any concentration of CA-125 can be clearly diagnostic of malignancy.     

The correlation between plasma fibrinogen levels and the clinical features of patients with ovarian carcinoma

Pre-operative plasma levels of fibrinogen, plasma prothrombin time, activated partial thromboplastin time and thrombin time (TT) were retrospectively examined in 105 patients with ovarian carcinoma and 21 control patients with benign ovarian tumour. Plasma cancer antigen 125 (CA-125) levels, pathological type, age, body mass index and blood group were evaluated. The TTs of patients with stage III and stage IV ovarian carcinoma were significantly shorter than in controls. Levels of plasma fibrinogen in patients with stage III and IV ovarian carcinoma were higher than those in patients with stage I and II ovarian carcinoma and the controls. There was a positive relationship between levels of plasma CA-125 and plasma fibrinogen in patients with stage II malignancy. There were no significant differences between plasma fibrinogen levels in patients of different age, BMI, blood group and pathological type. Shorter TT was an indication of advanced stage ovarian carcinoma, and fibrinogen was associated with the peritoneal carcinomatosis of ovarian carcinoma.