Role of cancer antigen-125 from pleural & ascitic fluid samples in non malignant conditions.
ABSTRACT CA-125, an ovarian tumor marker is known to increase in non malignant conditions such as tubercular and non tubercular pleuritis and ascites. We undertook this study to evaluate non-specific rise in CA-125 levels in conditions associated with pleural effusion and ascites and also to understand the mechanism of its secretion.
CA-125 levels in 38 pleural and 46 ascitic fluid samples from non malignant cases and 10 blood samples from pulmonary tuberculosis cases were estimated by ELISA. The ascitic fluid samples were collected from cases of bacterial peritonitis, tuberculosis, hepatitis, cirrhosis of other aetiology and pleural fluid samples were from cases of tubercular, pyogenic, cardiomegaly and other conditions.
Both ascitic and pleural fluid samples (transudative and exudative) showed elevated CA- 125 levels. The CA-125 levels were significantly higher in ascitic fluid samples than in pleural fluid samples.
Our findings showed that elevated levels of CA-125 in pleural and ascitic fluid could be because of varied aetiologies which need to be ruled out before considering malignancy. Peritoneum has a greater capacity to secrete CA-125 than the pleural epithelium and the secretion occurs following inflammation or mechanical distress. Pulmonary tuberculosis as a closed lesion without involvement of pleural epithelium does not evoke high CA-125 release.
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ABSTRACT: Pleural effusion is a commonly encountered problem in clinical practice, and pleural fluid analysis is usually the first step towards identifying the underlying etiology. Numerous studies have been published analyzing the potential utility of measuring biomarkers in pleural fluid as possible indicators of a malignant effusion; however, there are no studies that have examined the presence of human epididymis 4 (HE4) in pleural effusions. The aims of this study were to assess pleural effusion and serum concentrations of HE4 in patients with different types of pleural effusions and to evaluate the diagnostic performance of HE4 in detecting malignant pleural effusion. A prospective cohort study was carried out of 88 consecutive patients presenting with pleural effusions. The patients were divided into three groups: 22 patients with transudative effusions, 32 patients with non-malignant exudative effusions, and 34 patients with malignant pleural effusions. Blood and pleural fluid HE4 levels were measured using immunoassay. Both serum HE4 levels and pleural effusion HE4 levels were significantly higher in patients with malignant effusions than in patients with transudative or non-malignant exudative effusions. A pleural fluid HE4 cutoff value of 1,675 pmol/L was found to predict malignant pleural effusions with a diagnostic sensitivity of 85.3 % and specificity of 90.7 %. The current study reports a novel finding of increased serum and pleural fluid HE4 levels in patients with malignant effusions compared to non-malignant effusions. This finding has the potential to strengthen the diagnostic performance of tumor markers in detecting malignant pleural effusions.Tumor Biology 06/2012; 33(5):1701-7. · 2.84 Impact Factor
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ABSTRACT: Cancer antigen-125 is a high molecular weight glycoprotein used mainly for the diagnosis of ovarian carcinoma. However, elevation of cancer antigen-125 is observed in many benign conditions specially in liver cirrhosis but the reason behind the elevation remains unknown. Similarly intercellular adhesion molecule (ICAM-1) elevation is reported in liver cirrhosis but its role played in liver cirrhosis and ascites is unclear. Methods: A total of 76 patients were involved in the study diagnosed with liver cirrhosis, Budd-Chairi syndrome,and tuberculous peritonitis. The degree of ascites was graded according to standard criteria into mild, moderate and severe. Cancer antigen-125 levels and sICAM-1 levels of all the patients were measured along with other liver parameters to evaluate the association of CA-125 and sICAM-1with ascites. Results: When cancer antigen-125 levels of liver cirrhosis patients were correlated with ascites a strong correlation was observed with the degree of ascites but no association was seen with liver function parameters. A significant difference was shown when liver cirrhosis patients with ascites were compared with liver cirrhosis patients without ascites (p < 0.05). All the patients with ascites had elevated levels of CA-125 (mean: 261.11 U/mL ± 118.15 U/mL) whereas most of the patients without ascites had CA-125 levels under the normal range. A strong correlation (p < 0.05) is seen between CA-125 level and the degree of ascites. Elevated levels of sICAM-1 were observed in liver cirrhosis patients with ascites as well as in patients with other benign diseases with ascites (mean sICAM-1:7.23 ± 4.12 ng/mL and 6.67 ± 2.99 ng/mL, respectively). When sICAM levels of liver cirrhosis patients with and without ascites were compared a significant difference (p < 0.05) is observed. Conclusions: The elevation of cancer antigen-125 in liver cirrhosis is specific to ascites. The mesothelial cells of the peritoneum chiefly contribute to the elevation of cancer antigen-125 along with the large surface area of the peritoneum. Therefore, CA-125 can be used as a good marker for early diagnosis of ascites and CA-125 has no relationship with the etiology of diseases in benign ascites. ICAM-1 plays a key role in the formation of ascites by influencing the endothelial-vascular permeability and therefore it along with CA-125 can be used as markers or alternative tools to diagnose ascites and to monitor the progression and severity of the disease.Clinical laboratory 01/2014; 60(3). · 1.08 Impact Factor
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ABSTRACT: FDA-cleared ovarian cancer biomarkers are limited to CA-125 and HE4 for monitoring and recurrence and OVA1, a multivariate panel consisting of CA-125 and four additional biomarkers, for referring patients to a specialist. Due to relatively poor performance of these tests, more accurate and broadly applicable biomarkers are needed. We evaluated the dysregulation of 259 candidate cancer markers in serum samples from 499 patients. Sera were collected prospectively at 11 monitored sites under a single well-defined protocol. All stages of ovarian cancer and common benign gynecological conditions were represented. To ensure consistency and comparability of biomarker comparisons, all measurements were performed on a single platform, at a single site, using a panel of rigorously calibrated, qualified, high-throughput, multiplexed immunoassays and all analyses were conducted using the same software. Each marker was evaluated independently for its ability to differentiate ovarian cancer from benign conditions. A total of 175 markers were dysregulated in the cancer samples. HE4 (AUC=0.933) and CA-125 (AUC=0.907) were the most informative biomarkers, followed by IL-2 receptor α, α1-antitrypsin, C-reactive protein, YKL-40, cellular fibronectin, CA-72-4 and prostasin (AUC>0.800). To improve the discrimination between cancer and benign conditions, a simple multivariate combination of markers was explored using logistic regression. When combined into a single panel, the nine most informative individual biomarkers yielded an AUC value of 0.950, significantly higher than obtained when combining the markers in the OVA1 panel (AUC 0.912). Additionally, at a threshold sensitivity of 90%, the combination of the top 9 markers gave 88.9% specificity compared to 63.4% specificity for the OVA1 markers. Although a blinded validation study has not yet been performed, these results indicate that alternative biomarker combinations might lead to significant improvements in the detection of ovarian cancer.PLoS ONE 01/2011; 6(12):e29533. · 3.53 Impact Factor