CA 125: The past and future

Division of Medicine, University of Texas M.D. Anderson Cancer Center, Houston, USA.
The International journal of biological markers (Impact Factor: 1.37). 11/1997; 13(4):179-87.
Source: PubMed


Over the last 15 years, substantial progress has been made in understanding the potential and the limitations of the CA 125 assay. More than 2000 papers have been published concerning laboratory and clinical studies of CA 125. The original CA 125 assay utilized the OC 125 antibody that recognizes the CA 125 epitope on a high molecular weight glycoprotein. Despite repeated attempts, the gene encoding the peptide component has not yet been cloned. Monoclonal antibodies have been raised against other epitopes expressed by this molecule, leading to the development of the CA 125-II assay that exhibits less day-to-day variation. Using either assay, elevated levels of CA 125 are detected in a number of benign conditions, including endometriosis. CA 125 is most consistently elevated in epithelial ovarian cancer, but can be expressed in a number of gynecologic (endometrial, fallopian tube) and non-gynecologic (pancreatic, breast, colon and lung) cancers. The best established application of the CA 125 assay is in monitoring ovarian cancer. The rate of decline in CA 125 during primary chemotherapy has been an important independent prognostic factor in several multivariate analyses. Persistent elevation of CA 125 at the time of a second look surgical surveillance procedure predicts residual disease with > 95% specificity. Rising CA 125 values have preceded clinical detection of recurrent disease by at least 3 months in most, but not all studies. Given the modest activity of salvage chemotherapy, this information has not yet impacted on survival. Rising CA 125 during subsequent chemotherapy has been associated with progressive disease in more than 90% of cases. CA 125 may serve as an effective surrogate marker for clinical response in phase II trials of new drugs. CA 125 levels can aid in distinguishing malignant from benign pelvic masses, permitting effective triage of patients for primary surgery. Early detection of ovarian cancer remains the most promising application of CA 125. An algorithm has been developed that estimates the risk of ovarian cancer (ROC) based upon the level and trend of CA 125 values. A major trial has been initiated that uses the ROC algorithm to trigger transvaginal sonography and/or subsequent laparotomy. Such a trial could demonstrate improvement in survival through early detection. This strategy should provide adequate specificity, but sensitivity for early stage disease may not be optimal. In the future, improved sensitivity may be attained using multiple markers and neural network analysis. Most serum tumor markers have been proteins or carbohydrates, but lipid markers such as lysophosphatidic acid deserve evaluation. Genomic and proteonomic technologies should identify additional novel markers.

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    • "An elevated serum level of Ca-125 is a nonspecific marker of ovarian cancer. It may also be elevated in various gynecological and nongynecological conditions such as tuberculous peritonitis, endometriosis, menstruation, pelvic infection, peritonitis, pancreatitis, hepatitis, nephrotic syndrome, pericarditis , and pneumonia [16]. Several case series of tuberculous peritonitis mimicking ovarian cancer with elevated Ca-125 levels have been reported [17] [18]. "
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    ABSTRACT: We describe a rare case of fatal disseminated tuberculous peritonitis in a young woman with rapid progressive clinical course following spontaneous abortion of 20-week gestation. Clinical and laboratory findings were initially unremarkable. She underwent diagnostic laparoscopy which revealed numerous tiny implants on the peritoneum and viscera. Histopathology showed chronic caseating granulomas, and the tissue culture grew Mycobacterium tuberculosis. At fifth day of the antituberculous treatment multiorgan failure occurred in terms of pulmonary, hepatic, and renal insufficiency. She developed refractory metabolic acidosis with coagulopathy and pancytopenia, and she died of acute respiratory distress syndrome and septic shock on her twelfth day of hospitalization.
    03/2014; 2014:125609. DOI:10.1155/2014/125609
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    • "CA-125 is currently the most common tumormarker for ovarian cancer [18], but its use for the detection of ovarian cancer at an early stage is very limited since CA-125 level is elevated only in ~50% of stage I ovarian cancer [19]. Considering that ~19% of ovarian cancer cases are first detected at stage I with 5-year survival rate ~93% and that majority of ovarian cancer patients (67–74%) are diagnosed at much later stages (stages III and IV) mostly with metastatic status [20], it is of critical importance to develop biomarkers which can provide reliable information for the early screening of ovarian cancer. "
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    ABSTRACT: Changes of glycosylation pattern in serum proteins have been linked to various diseases including cancer, suggesting possible development of novel biomarkers based on the glycomic analysis. In this study, N-linked glycans from human serum were quantitatively profiled by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) and compared between healthy controls and ovarian cancer patients. A training set consisting of 40 healthy controls and 40 ovarian cancer cases demonstrated an inverse correlation between P value of ANOVA and area under the curve (AUC) of each candidate biomarker peak from MALDI-TOF MS, providing standards for the classification. A multibiomarker panel composed of 15 MALDI-TOF MS peaks resulted in AUC of 0.89, 80~90% sensitivity, and 70~83% specificity in the training set. The performance of the biomarker panel was validated in a separate blind test set composed of 23 healthy controls and 37 ovarian cancer patients, leading to 81~84% sensitivity and 83% specificity with cut-off values determined by the training set. Sensitivity of CA-125, the most widely used ovarian cancer marker, was 74% in the training set and 78% in the test set, respectively. These results indicate that MALDI-TOF MS-mediated serum N-glycan analysis could provide critical information for the screening of ovarian cancer.
    Disease markers 02/2014; 2014(2):634289. DOI:10.1155/2014/634289 · 1.56 Impact Factor
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    • "The sensitivity of CA125 for recurrence is 62-94% and the specificity is 91-100% 25, 34. The CA125 level rises at least 3 months before recurrence and there is a median lag time of two months between the elevation in CA125 and findings on imaging studies 35, 36. The GCIG defines recurrent ovarian cancer as elevation of CA125 ≥ twice the upper limit of normal on two occasions at least one week apart in those patients who had an elevated marker at diagnosis with normalization after treatment 16. "
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    ABSTRACT: Epithelial ovarian cancer is the leading cause of death among gynecologic malignancies. Treatment of recurrent ovarian cancer remains a challenge despite advances in surgical and chemotherapeutic options. A goal of many providers is to detect recurrences as early as possible and initiate treatment though there is controversy as to whether this impacts outcome. Elevations in CA125 and radiological findings may precede symptoms of recurrence by several months. While detection of recurrences by physical exam alone is unusual, a thorough exam in conjunction with reported symptoms and elevated CA125 is sufficient to detect 80-90% of recurrences. A spiral CT scan may be used to confirm recurrence in the setting of asymptomatic CA125 elevation and a PET/CT can yield additional insight if the CT is inconclusive. Initiating chemotherapy prior to the development of symptoms, even in the setting of elevated CA125, does not impact overall survival primarily because the efficacy of available treatments in the recurrent setting is poor. More information about tumor biology and ways to predict which patients will benefit from available treatment options is required. Consequently, the approach to post-treatment surveillance should be individualized taking into account the clinical benefit of the second-line therapy, versus the costs and morbidity of the surveillance method.
    Journal of Cancer 01/2014; 5(1):25-30. DOI:10.7150/jca.7810 · 3.27 Impact Factor
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