CA 125: The past and future
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.
Available from: Samah Fathy
- "Erbağci et al.  reported that excess adipose tissue in obesity has a positive effect on the expression of CA-125. Bast et al.  also stressed that elevated levels of CA-125 are consistently detected in conditions such as endometriosis, epithelial ovarian cancer, as well as pancreatic, breast, colon and lung cancers. Disruption of the normal balance between cell proliferation , differentiation, and apoptosis in our obese subjects could therefore account for the significant expression of CA-125 observed in this study. "
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ABSTRACT: Introduction: Obesity increases production of adipose tissue-derived proteins, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Also there are elevated levels of C-reactive protein (CRP) and IL-6, CD8, and CD4, indicating chronic subclinical inflammation. Since obesity represents a serious risk factor in several metabolic diseases, identifying the status of carbohydrate antigen-125 (CA-125) would further link obesity and tumors. Aim: To examine the effect of weight loss by laparoscopic sleeve gastrectomy (LSG) on plasma CRP, lipid profiles and CA-125 level in morbidly obese patients. Material and methods: This prospective study was conducted in the Surgery Department, Fayoum University Hospital, between August 2013 and September 2015. To assess the effect of excess weight loss following this operation CRP, lipid profile and CA-125 were measured before and 12 months after the LSG operation for weight loss. The study included 30 cases of morbidly obese patients: 30 (100%) females aged 23-55 years who were considered clinically obese with a mean body mass index of 42.71 ±4.3 (38-46) kg/m2 and mean age of 40.3 ±8.5 (23-55) years. The National Institute of Health (NIH) inclusion criteria for bariatric surgery were used. Results: A mean weight loss of 29.30% decreased plasma CRP, triglycerides, total cholesterol and low-density lipoprotein cholesterol (HDL cholesterol), CA-125 level and increased high-density lipoprotein cholesterol (HDL cholesterol) The percentage weight loss was significantly associated with changes in plasma CRP, triglycerides, total cholesterol, total HDL cholesterol and CA-125. Conclusions: Weight loss by LSG improves inflammation, dyslipidemia and CA-125 level.
Available from: Murat Ozekinci
- "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 . Several case series of tuberculous peritonitis mimicking ovarian cancer with elevated Ca-125 levels have been reported  . "
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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.
Available from: PubMed Central
- "CA-125 is currently the most common tumormarker for ovarian cancer , 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 . 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 , 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
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.
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