Cancer Antigen CA125 Research Articles

B-309 Evaluation of the Analytical Performance of Breast and Ovarian Cancer Antigen Assays on the Atellica CI Analyzer

Abstract Background The Atellica® CI Analyzer is an automated, high-throughput integrated chemistry and immunoassay analyzer utilizing both Atellica® CH and Atellica® IM Assays. This study evaluated the analytical performance of the Atellica IM breast cancer antigen CA 15-3™ (CA 15-3) and the ovarian cancer antigen CA 125II™ (CA 125II) Assays on the Atellica CI Analyzer. Methods Precision studies were performed according to CLSI EP05-A3 using native and contrived human serum samples as well as contrived horse serum samples for CA 15-3. One aliquot of each sample pool was tested in duplicate in two runs per day ≥2 hours apart on each analyzer for ≥20 days. Precision studies were evaluated with one reagent lot on two systems. Method comparison studies were performed using three reagent lots according to CLSI EP09c. Individual native and contrived human serum samples were analyzed using the Atellica IM CA 15-3 and CA 125II Assays on the Atellica IM Analyzer and the Atellica CI Analyzer. LoB, LoD, and LoQ were determined as described in CLSI EP17-A2. Results Representative precision and method comparison results for each assay are listed in the table. For the two assays tested, repeatability and within-lab %CVs were <2.4% and <6.9%, respectively. Slopes determined by the weighted Deming linear regression model were approximately 1. Detection capability for the Atellica IM CA 15-3 Assay on the Atellica CI Analyzer was estimated to be 1.0 U/mL, 2.0 U/mL and 3.0 U/mL for LoB, LoD, and LoQ, respectively. When using the Atellica IM CA 125II Assay, detection capability was estimated to be 2.0 U/mL, 3.0 U/mL and 3.0 U/mL for LoB, LoD, and LoQ, respectively. Conclusions Evaluation of the Atellica IM CA 15-3 and CA 125II Assays using the Atellica CI Analyzer demonstrated good precision and equivalent performance compared to the same assays on the Atellica IM Analyzer.

Role of serum cancer antigen CA-125 in the First Trimester Threatened Miscarriage

Role of serum cancer antigen CA-125 in the First Trimester Threatened Miscarriage

Tumor Markers in Dogs with Mammary Gland Tumors

Abstract The aim of this study was to determine and compare values of carcinoembryonic antigen (CEA) and cancer antigen (CA 15-3) in 50 bitches with mammary tumors and 150 clinically healthy dogs. A modified procedure was used to determine the CEA and CA 15-3 markers with the human kits using the radioimmunoassay method (RIA). Samples collected from extirpated tumors of mammary glands were histologically processed and classified as per WHO guidelines. The mean values of the carcinoembryonic antigen markers ± SD were as follows: control group 0.89 ± 0.79, group with mammary gland tumor 1.53 ± 1.15. The values of cancer antigen markers CA 15-3 ± SD were: 1.52 ± 0.66 and 2.87 ± 1.11, respectively. The statistical significance for the carcinoembryonic antigen marker between groups was P < 0.0001. The cancer antigen CA 15-3 values between groups were also statistically significant with P < 0.0001. The results of the present study show that there are significant differences in both antigens between the control group and groups with mammary gland tumor in dogs.

CORRELATION OF CA 15.3 LEVELS WITH METASTASIS IN BREAST CANCER

Objectives: The objective is to measure the serum levels of Cancer Antigen CA 15.3 in breast cancer patients with metastasis and without metastasis and compare the mean values between them. The study investigated the correlation between CA 15.3 levels and metastasis in breast cancer. Methods: The study was conducted with 45 female patients in a tertiary care center in India, and metastatic evaluation was done using positron emission tomography–computed tomography. Results: The results indicated that CA 15.3 levels were significantly higher in the metastatic group compared to the non-metastatic group. Conclusion: CA 15.3 has the potential as a diagnostic tool for early detection of metastases in breast cancer patients.

Prognostic Significance of Preoperative NLR, MLR, and PLR Values in Predicting the Outcome of Primary Cytoreductive Surgery in Serous Epithelial Ovarian Cancer

(1) The degree of cytoreduction achieved during primary debulking surgery (PDS) is an important prognostic factor for the survival of patients with epithelial ovarian cancer (EOC). Our aim was to investigate the prognostic value of preoperative laboratory parameters for the outcome of PDS. (2) We analyzed the preoperative laboratory parameters of 150 serous EOC patients who underwent PDS between 2006 and 2013. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off values of the variables for predicting the PDS outcome. We used binary logistic regression to examine the independent predictive value of the factors for incomplete cytoreduction. (3) Among the parameters, we established optimal cut-off values for cancer antigen (Ca)-125, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) to predict the outcome of PDS. The results of binary logistic regression showed that stage (FIGO III-IV), MLR (>0.305), and Ca-125 (>169.15 kU/L) were independent significant predictors of the degree of tumor reduction achieved during PDS. (4) In the future, MLR, especially in combination with other parameters, may be useful in determining prognosis and selecting the best treatment option (PDS or neoadjuvant chemotherapy + interval debulking surgery) for ovarian cancer patients.

Application of Various Optical and Electrochemical Nanobiosensors for Detecting Cancer Antigen 125 (CA-125): A Review.

Nowadays, diagnosing early-stage cancers can be vital for saving patients and dramatically decreases mortality rates. Therefore, specificity and sensitivity in the detection of cancer antigens should be elaborately ensured. Some early-stage cancers can be diagnosed via detecting the cancer antigen CA-125, such as ovarian cancer, and required treatments can be applied more efficiently. Thus, detection of CA-125 by employing various optical or electrochemical biosensors is a preliminary and crucial step to treating cancers. In this review, a diverse range of optical and electrochemical means of detecting CA-125 are reviewed. Furthermore, an applicable comparison of their performance and sensitivity is provided, several commercial detection kits are investigated, and their applications are compared and discussed to determine whether they are applicable and accurate enough.

New Quantum-Dot-Based Fluorescent Immunosensor for Cancer Biomarker Detection

Cancer antigen 15-3 (CA 15-3) is a biomarker for breast cancer used to monitor response to treatments and disease recurrence. The present work demonstrates the preparation and application of a fluorescent biosensor for ultrasensitive detection of the cancer antigen CA 15-3 protein tumor marker using mercaptopropionic-acid-functionalized cadmium telluride (CdTe@MPA) quantum dots (QDs) conjugated with CA 15-3 antibodies. First, the QDs were synthesized by the hydrothermal route, resulting in spherical nanoparticles up to 3.50 nm in diameter. Subsequently, the QD conjugates were characterized by Fourier transform infrared spectroscopy (FTIR), UV absorption, and fluorescence. The interaction between the conjugates and the protein was studied by fluorescence spectroscopy in buffer and in 10-fold diluted commercial human serum. Calibration in spiked serum samples gave a detection limit of 0.027 U/mL, 1000-fold lower than the clinical limit for CA 15-3 (25 U/mL to 30 U/mL), indicating that this is an ultrasensitive technique. In addition, a rapid response was obtained within 10 min. The biosensor was selective in the presence of the interfering serum proteins BSA, CEA, and CA-125, with a maximum interference of 2% for BSA. The percent recovery was close to 100% with maximum relative standard deviation (RSD%) values of 1.56. Overall, the developed CA 15-3 biosensor provides a simple and sensitive method for ultrasensitive monitoring of breast cancer, as well as the ability to detect other molecules of interest in human serum matrices.

Inflammatory Mediators (CA125, CRP) and Uric Acid in Association with Severity of Preeclampsia in North Kordofan State, Western Sudan

Introduction: Inflammatory mediators could be laboratory markers of preeclampsia, as the induction of an inflammatory process within the placenta may trigger the expression of cancer antigen 125(CA125), C-reactive protein (CRP) and uric acid (UA). Regarding the pathophysiology of pre-eclampsia, there is defective trophoblastic invasion of uteroplacental blood vessels that leads to placental ischemia, and induction of an inflammatory process within the placenta.
 Objective: To evaluate the association of serum levels of cancer antigen (CA125), C-reactive protein (CRP) and serum uric acid with the Severity of Preeclampsia.
 Materials and Methods: The study recruited 200 singleton Sudanese pregnant women. These participants were divided into two groups: control (n = 100) and cases (n = 100). The cases were further subdivided into; mild preeclampsia (n =46), and severe preeclampsia (n = 54). The study groups were well-matched in maternal age, gestational age and body mass index. Blood samples were taken for measurement of serum cancer antigen-CA125, uric acid and C - reactive protein using immune- assay and enzymatic automated chemical analysis.
 Results: The mean levels of cancer antigen-CA125 in mild and severe preeclampsia groups were; 21.94±5.08 (IU/ml) and 40.77±9.82 (IU/ml) respectively, which were significantly higher, (P<0.001) in comparison with the control group (16.88±7.36 (IU/ml). The mean levels of C-reactive protein in mild and severe preeclampsia were; 15.17±5.35 (mg/L), 31.49±12.56 (mg/L) respectively. There was significant difference in their levels, compared to the control group (4.79±1.78 (mg/L), (P<0.01). Also, the mean levels of uric acid in mild and severe cases were; 6.44±1.98 and 7.37±2.00 which was significantly higher, in comparison with the control (4.00±0.61); (P<0.001). The level of uric acid also, showed significant difference within the case (severe and mild) group (P<0.05). CA125, CRP and UA level‎s correlated positively with Mean Arterial blood pressure (MAP), (r>0.7; P < 0.001). ROC curve validate the utility of these biomarker for the detection of preeclampsia severity (AUC>0. 8; P < 0.001).
 Conclusion: Serum cancer antigen 125(CA125), C- reactive protein and uric acid in studied preeclampsia groups were found to be significantly higher compared with the control group, and the rises were directly associated with the severity of preeclampsia.

Network Meta-analysis of peroral Chinese patent medicines for activating blood and resolving stasis in treatment of endometriosis

Network Meta-analysis was performed to systematically compare the efficacy of different Chinese patent medicines for activating blood and resolving stasis in the treatment of endometriosis and to provide evidence-based references for clinical medication regimens. The relevant randomized controlled trials(RCTs) involving Chinese patent medicines combined with conventional treatment(experimental group) vs conventional treatment(control group) were retrieved from Chinese and English literature databases. The bias risk assessment tool recommended in Cochrane handbook 5.3 was used to evaluate the quality of the included studies. The result data of each outcome index was extracted for network Meta-analysis in Stata 15.0. A total of 44 RCTs were included in this study, involving 4 345 patients and 9 Chinese patent medicines. The network Meta-analysis revealed the following trends.(1)In terms of reducing the visual analogue scale(VAS) scores, Dan'e Fukang Plaster+conventional treatment>Xuefu Zhuyu Capsules+conventional treatment>Gongliuxiao Capsules+conventional treatment.(2)In terms of reducing cancer antigen CA125, Xiaojin Capsules+conventional treatment>Shaofu Zhuyu Granules+conventional treatment>Dan'e Fukang Plaster+conventional treatment.(3)In terms of reducing estradiol(E_2), Gongliuxiao Capsules+conventional treatment>Xiaojin Capsules+conventional treatment>Sanjie Zhentong Capsules+conventional treatment.(4) In terms of reducing recurrence rate, Guizhi Fuling Capsules+conventional treatment>Xuefu Zhuyu Capsules+conventional treatment>Dan'e Fukang Plaster+conventional treatment. The peroral Chinese patent medicines for activating blood and resolving stasis combined with conventional treatment have better efficacy in the treatment of endometriosis than conventional treatment. However, considering the low quality of the included literature, large-scale high-quality clinical trials are needed in the future research.

The Role of Mesothelin Expression in Serous Ovarian Carcinoma: Impacts on Diagnosis, Prognosis, and Therapeutic Targets.

Simple SummaryOvarian cancer is the most lethal gynaecological malignancy, of which serous carcinoma is the most common subtype. The lack of symptoms and sensitive diagnostic tests for the early stages of its development may explain why diagnosis often occurs late, when the neoplasm has already spread outside the pelvis. Currently, the standard treatment for high-grade serous ovarian carcinomas (HSOCs) involves cytoreductive surgery followed by platinum-based systematic chemotherapy, which does not reduce either recurrence or mortality. Despite intense efforts to develop novel therapies using new chemotherapeutic agents, such as anti-angiogenesis agents and poly (ADP-ribose)-polymerase inhibitors, to improve patient outcomes, the five-year survival for this malignancy remains low. Therefore, it is important to identify new targetable molecules for the early diagnosis, monitoring, and treatment of this malignancy. The aim of this review is to discuss the role of mesothelin in serous ovarian carcinomas, focusing on diagnostic, prognostic, and therapeutic perspectives.Mesothelin (MSLN) is a protein expressed in the mesothelial cell lining of the pleura, peritoneum, and pericardium; its biological functions in normal cells are still unknown. Experimental studies using knockout mice have suggested that this molecule does not play an important role in development and reproduction. In contrast, it has been observed that this molecule is produced in abnormal amounts in several malignant neoplasms, such as mesotheliomas and pancreatic adenocarcinomas. Many molecular studies have also demonstrated that mesothelin is overexpressed in HSOCs. Here, we discuss the current knowledge of mesothelin and focus on its role in clinical and pathological diagnoses, as well as its impact on the prognosis of HSOC. Moreover, regarding the binding of MSLN to the ovarian cancer antigen CA125, which has been demonstrated in many studies, we also report on signal transduction pathways that may play an important role in the spread and neoplastic progression of this lethal neoplasm. Given that mesothelin is overexpressed in many solid tumours and has antigenic properties, this molecule could be considered an antigenic target for the treatment of many malignancies. Consequently, we also review the literature to report on mesothelin-targeting therapies for HSOC that have been recently investigated in many clinical studies.

A novel electrochemical sensor for monitoring ovarian cancer tumor protein CA 125 on benzothiophene derivative based electrodes

COVID-19 crisis affects ovarium cancer patients seriously. Thus, it is vital to diagnose ovarium cancer, one of the most common types of cancer diagnosed and the causes of death of women around the world, at early stages. Herein, 5-(2-phenylbenzo[b]thiophen-3-yl) thiophene-2-carbaldehyde (PTTC)-based sensor is designed to detect CA-125 more precisely and rapidly via electrochemical methods. PTTC, novel benzothiophene derivative, is synthesized by electrophilic cyclization reactions and Pd-catalyst coupling reactions. Then, PTTC is dispersed homogeneously in Nafion solution, and an ink is obtained. This ink is transferred onto the glassy carbon electrode and CA-125 is incubated on this electrode. Cyclic voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy measurements are employed to determine sensitivity and reliability of CA-125 on PTTC based GCE electrode. The effect of CA 125 concentration, incubation time, scan rate studies are performed by CV to determine the optimum conditions. Optimum conditions are found as 3 μL PTTC loading, 5000 ng/mL CA125 antigen concentration and 30 min incubation time. Linear range of the PTTC based GCE electrode prepared at optimum conditions are obtained by DPV as 1–100 ng/ml.Limit of detection and limit of quantification values were obtained as 0.0096 ng/mL and 0.0288 ng/mL, respectively. Interference and artificial serum results reveal that this electrode is a promising electrode for CA125 antigen determination for the ovarium cancer. PTTC is a novel and unique material for the detection of ovarium cancer antigen CA-125 and promising for CA-125 antigen detection.

S1772 A Giant Hyperplastic Colorectal Polyp With No Malignant Features

Introduction: Hyperplastic polyps (HP) are a benign subgroup of serrated polyps. HP larger than 10 mm is considered a large polyp and larger than 2 cm carry a risk for malignancy. A case of near obstructing giant hyperplastic polyp of the recto-sigmoid colon with no malignant features is presented with a topic review and proposed further follow-up. Case Description/Methods: A 29-year-old African American man presented to the gastroenterology clinic with a 1-year history of early satiety, intermittent rectal bleeding, alteration in bowel habits, and weight loss. Upper and lower endoscopies identified a large pedunculated mass with near-complete obstruction in the recto-sigmoid colon [Figure 1A]. Biopsies show hyperplastic mucosa with no evidence of a malignant process. Imaging revealed distal colonic mass extending over a 6 cm segment [Figure 1B]. CEA and cancer antigen CA 19-9 markers were unremarkable. Laparoscopic sigmoid resection was performed. Histology reported pedunculated polyp 2.5 x 2.5 x 1.8 cm and 2 cm stalk with serrated appearance, hyperplasia, and no evidence of malignancy [Figure 1C]. Postoperative course was uneventful, with improvement in appetite and weight gain. Genetics evaluation deferred further testing. Discussion: HP are the most abundant type and now believed to be a subgroup of serrated polyps (SP). SP are classified into two main subgroups based on malignant potential. The majority of the serrated carcinomas arising from HP follow BRAF and KRAS pathways. Microsatellite instability has also been associated [1]. Serrated polyposis syndrome is associated with the risk of colorectal cancer. Due to the inability of subtracting a single responsible gene, other syndromes should be excluded. Polyps larger than 1 cm are classified as large, and exceeding 3 cm as a giant. Parallel to the size increases the malignant potential. Risk stratification of giant, pedunculated polyps is advised prior to endoscopy due to the risk of perforation and bleeding. Due to the concern for malignant transformation with obstructive signs and symptoms, surgical excision was advised.Further discussions are needed to establish clear guidelines for testing and surveillance of single giant non-malignant polyps. We propose our own management including surgical vs. endoscopic resection, genetic testing, and colonoscopy in 1,3, and 5- year intervals, followed by standard surveillance.Figure 1.: A. Abdominal CT scan. B. Colonoscopic view. C. Lower Endoscopic Ultrasound View. D. Histopathology.

Signal amplification strategy of label-free ultrasenstive electrochemical immunosensor based ternary Ag/TiO2/rGO nanocomposites for detecting breast cancer biomarker CA 15-3

Cancer Antigen 15-3 (CA 15-3) is a fast, non-invasive and reproducible significant biomarker diagnostic tool. More reliable, easy, and precise approaches for the detection of CA 15-3 are still urgently required. This study suggested a new label-free electrochemical immunosensor for the quantitative determination of the breast cancer antigen CA 15-3. Ternary silver/titanium dioxide/reduced graphene oxides (Ag/TiO2/rGO) nanocomposites were employed as a signal amplification platform for the developed immunosensor. A possible signal amplification mechanism of the amperometric detection was investigated by measuring the reduction of hydrogen peroxide and evaluating the electrocatalytic current response via the immunoreaction between CA 15-3 antibody-antigen on the surface of the developed Ag/TiO2/rGO nanocomposite immunosensor. The change in current response of the tested antigen in the presence of other interfering elements was lower than 5% revealing great selectivity in determining the breast cancer CA 15-3 antigen. Furthermore, a linear concentration 0.1–300 UmL−1 with a correlation coefficient of 0.9996 was achieved with a very low limit of detection (0.07 UmL−1) in human serum samples. The outcomes ensured that the development of such type of immunosensors can open the gate to fabricate many others suitable for the early detection of tumor markers with more accuracy and convenience.

Machine learning-based LIBS spectrum analysis of human blood plasma allows ovarian cancer diagnosis.

Early-stage screening and diagnosis of ovarian cancer represent an urgent need in medicine. Usual ultrasound imaging and cancer antigen CA-125 test when prescribed to a suspicious population still require reconfirmations. Spectroscopic analyses of blood, at the molecular and atomic levels, provide useful supplementary tests when coupled with effective information extraction methods. Laser-induced breakdown spectroscopy (LIBS) was employed in this work to record the elemental fingerprint of human blood plasma. A machine learning data treatment process was developed combining feature selection and regression with a back-propagation neural network, resulting in classification models for cancer detection among 176 blood plasma samples collected from patients, including also ovarian cyst and normal cases. Cancer diagnosis sensitivity and specificity of respectively 71.4% and 86.5% were obtained for randomly selected validation samples.

The evolving role of MUC16 (CA125) in the transformation of ovarian cells and the progression of neoplasia.

MUC16 (the cancer antigen CA125) is the most commonly used serum biomarker in epithelial ovarian cancer, with increasing levels reflecting disease progression. It is a transmembrane glycoprotein with multiple isoforms, undergoing significant changes through the metastatic process. Aberrant glycosylation and cleavage with overexpression of a small membrane-bound fragment consist MUC16-related mechanisms that enhance malignant potential. Even MUC16 knockdown can induce an aggressive phenotype but can also increase susceptibility to chemotherapy. Variable MUC16 functions help ovarian cancer cells avoid immune cytotoxicity, survive inside ascites and form metastases. This review provides a comprehensive insight into MUC16 transformations and interactions, with description of activated oncogenic signalling pathways, and adds new elements on the role of its differential glycosylation. By following the journey of the molecule from pre-malignant states to advanced stages of disease it demonstrates its behaviour, in relation to the phenotypic shifts and progression of ovarian cancer. Additionally, it presents proposed differences of MUC16 structure in normal/benign conditions and epithelial ovarian malignancy.

Biochemical study of Cancer Antigen CEA and CA 19-9 as prognostic markers in colorectal cancer (CRC)

Colorectal cancer is one of the most common types of cancer in the world. Several factors have been shown to put individuals at risk to CRC and these include age, the presence of polyps, inflammatory bowel disease, lifestyle, genetic background and family medical history. In the present study, we were related to the cancer antigen CEA and CA19-9 as prognostic markers in colorectal cancer. This may be helping us to detect colorectal cancer in an early stage. In this study, we have included 60 patients diagnosed with colorectal cancer. These patients were categorized as 10 patients between stage I-IV with disease dissemination and recurrence; 50 patients in between stage I- IV without dissemination and recurrence; 60 healthy controls. The cancer antigen CEA and Ca 19-9 were analyzed as prognostic markers in colorectal cancer. The statistical analysis was done by using SPSS software and expressed in terms of mean ± standard deviation. The p values (p˂0.005) were considered as statistically significant value. Person correlation between the cancer antigen CEA and CA-19-9 were analyzed. The cancer antigen CEA and Ca19-9 level were significantly increased in colorectal cancer patients as compared to the healthy controls group (p˂0.005). The significant Person correlation was observed in between CEA and CA19-9. The level of CEA and CA19-9 were significantly prognostic indicator in colorectal cancer. CEA and CA19-9 can be used as a diagnostic and prognostic marker for the screening of both colon and rectum cancer.

Gene expressions involved in immune system control and serum CA125 content in polycythemia vera. Tap

Polycythemia Vera (PV) is a slowly progressing blood cancer associated with myeloproliferative neoplasms. The disease is characterized by an abnormal proliferation of three cell types including red blood cells, white blood cells and platelets and a symptom of pruritus caused by release of itching agents of activated mast cells. The enhanced expression of several genes involved in immune system control including CTLA-4, PD-1 and LAG3 are linked to activation immune tolerance. Klotho gene has anti-aging, anti-inflammation and anti-cancer functions. The SHP gene group belongs to the tyrosine phosphatase protein signaling family that regulates cancer cell proliferation through maturation, migration and apoptosis and includes two main genes, SHP-1 and SHP-2. The increased serum content of cancer antigen CA125 is considered as a cancer marker of several blood and hematopoietic disorders. In this study, we conducted experiments to determine mRNA expression of above genes in PV patients by realtime-PCR and CA125 concentration by ELISA. Results showed that expression of klotho, LAG3, CTLA-4 and PD-1 genes was decreased in PV patients, indicating that the immune tolerance was inactivated in PV patients. CA125 concentration was significantly increased in PV patients compared to healthy individuals and interestingly, there was a positive association among three patients, who having increased CA125 concentration and biochemical indicators including LDH, AST and ALT. The results in this study provide an important reference document for further studies that serve for the early detection of PV disease.

Label-Free Detection of Ovarian Cancer Antigen CA125 by Surface Enhanced Raman Scattering.

Surface-enhanced Raman spectroscopy (SERS) has drawn attention in recent years for imaging biologicalmolecules as an analytical tool due to its label-free approach. The SERS approach can be used in tracking organic molecules and monitoring unique Raman spectra of the organic molecules bound to metal nanoparticles (NPs). In this paper, the molecular specifity of Raman Spectroscopy was used together with self-assembled monolayer of metallic AuNPs as a sensor platform in order to detect CA125 antibody-antigen probe molecules. Highly enhanced electromagnetic fields localized around neighboring AuNPs provide hot-spot construction due to the spatial distribution of SERS enhancement on the CA125 proteins at nM concentration level. Time resolved SERS mapping of CA125 antibody and antigen couples was recorded. Even though blinking behavior was observed for some cases, vast variety SERS signals from CA125 proteins were highly reproducible. Blinking behavior is attributed to single molecular detection. Distinguished feature of SERS mapping images of CA125 antibody and antigen with such a low concentration level is very promising for this technique to be used for diagnostic purposes.

Clinical Use and Optimal Cutoff Value of Ca15-3 in Evaluation of Adnexal Mass: Retrospective Cohort Study and Review of the Literature.

To estimate the diagnostic performance and reference values of serum cancer antigen (Ca)15-3 levels in the triage of adnexal masses. This retrospective cohort study was carried out in 481 patients referred to the Gynecology Department at Carmel Medical Center due to adnexal mass between years 2005 and 2012. All patients underwent surgery with histopathologically confirmed diagnosis and routine preoperative measurements of serum Ca125 and Ca15-3. Combination of Ca125 with Ca15-3 elevated the sensitivity of Ca125 alone (from 86.9% to 93.2%; P=0.029), along with reduction of its specificity (from 80.5% to 69.5%; P=0.005) in differentiation between malignant and benign cases. According to receiver operating characteristic curve, Ca15-3 level of 21 U/mL was shown to be the optimal reference value for malignancy detection. All cases with Ca15-3 levels above 44.5 U/mL were malignant, mostly of primary ovarian source. As Ca15-3 assessment allowed detection of significantly more malignancy cases, we believe that measurement of this marker in combination with Ca125 is worthwhile in patients presenting with adnexal masses. The cutoff of 21 U/mL seems to be the optimal value in this specific population. High Ca15-3 levels (above 44.5 U/mL) strongly direct to a diagnosis of malignancy, mostly of primary ovarian tumors rather than breast malignancy.

Analysis of CA125 antigen in normal human seminal plasma highlightsthe molecular heterogeneity of underlying glycosylated species

Cancer antigen CA125 represents an extracellular part of transmembrane mucin MUC16 and may be expressed in tissues of the male reproductive tract. It reaches human seminal plasma (hSP) after undergoing the main processes involved in protein speciation: synthesis, posttranslational modifications, compartmentalization, and auto/proteolytic degradation. This study was aimed at profiling CA125-immunoreactive species in hSP from healthy subjects as a specific and unexplored source of this tumor-associated antigen expressed under normal physiological conditions. High molecular mass components from total hSP and corresponding acid-soluble hSP preparations were analyzed. The results indicated that antibodies recognizing two distinct immunogenic areas of CA125 antigen exhibited a common pattern of immunoreactive bands affected by low pH and reducing agents. They comprise a large, heavily glycosylated moiety and a mixture of low glycosylated species ranging from 100 to 150 kDa. High molecular mass CA125-immunoreactive smears overlapped core 2 O-glycans and the Lex glycotope, the latter also being abundant on distinct lower molecular mass immunoreactive bands. Within the bulk of normal hSP mucins, the CA125 antigen is present in low amounts and resides on heterogeneously glycosylated species that may be proteolysis-derived and sensitive to redox environments. Both factors influence the composition of hSP and therefore might affect speciation of mucin16 under normal and pathological conditions.