Atomically Co-dispersed nitrogen-doped carbon for sensitive electrochemical immunoassay of breast cancer biomarker CA15-3.

The development of an ultrasensitive and precise measurement of a breast cancer biomarker (cancer antigen 15-3; CA15-3) in complex human serum is essential for the early diagnosis of cancer in groups of healthy populations and the treatment of patients. However, currently available testing technologies suffer from insufficient sensitivity toward CA15-3, which severely limits early large-scale screening of breast cancer patients. We report a versatile electrochemical immunoassay method based on atomically cobalt-dispersed nitrogen-doped carbon (Co-NC)-modified disposable screen-printed carbon electrode (SPCE) with alkaline phosphatase (ALP) and its metabolite, ascorbic acid 2-phosphate (AAP), as the electrochemical labeling and redox signaling unit for sensitive detection of low-abundance CA15-3. During electrochemical detection by differential pulse voltammetry (DPV), it was found that the Co-NC-SPCE electrode did not have a current signal response to the AAP substrate; however, it had an extremely favorable response current to ascorbic acid (AA). Based on the above principle, the target CA15-3-triggered immunoassay enriched ALP-catalyzed AAP produces a large amount of AA, resulting in a significant change in the system current signal, thereby realizing the highly sensitive detection of CA15-3. Under the optimal AAP substrate concentration and ALP catalysis time, the Co-NC-SPCE-based electrochemical immunoassay demonstrated a good DPV current for CA15-3 in the assay interval of 1.0 mU/mL to 10,000 mU/mL, with a calculated limit of detection of 0.38 mU/mL. Since Co-NC-SPCE has an excellent DPV current response to AA and employs split-type scheme, the constructed electrochemical immunoassay has the merits of high preciseness and anti-interference, and its clinical diagnostic results are comparable to those of commercial kits.

Breast cancer detection based on cancer antigen 15-3; emphasis on optical and electrochemical methods: A review.

Cancer antigen 15-3 (CA 15-3) is a crucial marker used in the diagnosis and monitoring of breast cancer (BC). The demand for early and precise cancer detection has grown, making the creation of biosensors that are highly sensitive and specific essential. This review paper provides a thorough examination of the progress made in optical and electrochemical biosensors for detecting the cancer biomarker CA 15-3. We focus on explaining their fundamental principles, sensitivity, specificity, and potential for point-of-care applications. The performance attributes of these biosensors are assessed by considering their limits of detection, reaction times, and operational stability, while also making comparisons to conventional methods of CA 15-3 detection. In addition, we explore the incorporation of nanomaterials and innovative transducer components to improve the performance of biosensors. This paper conducts a thorough examination of recent studies to identify the existing obstacles. It also suggests potential areas for future research in this fast progressing field.The paper provides insights into their advancement and utilization to enhance patient outcomes. Both categories of biosensors provide significant promise for the detection of CA 15-3 and offer distinct advantages compared to conventional analytical approaches.

An Innovative Approach for Tailoring Molecularly Imprinted Polymers for Biosensors-Application to Cancer Antigen 15-3.

This work presents a novel approach for tailoring molecularly imprinted polymers (MIPs) with a preliminary stage of atom transfer radical polymerization (ATRP), for a more precise definition of the imprinted cavity. A well-defined copolymer of acrylamide and N,N'-methylenebisacrylamide (PAAm-co-PMBAm) was synthesized by ATRP and applied to gold electrodes with the template, followed by a crosslinking reaction. The template was removed from the polymer matrix by enzymatic/chemical action. The surface modifications were monitored via electrochemical impedance spectroscopy (EIS), having the MIP polymer as a non-conducting film designed with affinity sites for CA15-3. The resulting biosensor exhibited a linear response to CA15-3 log concentrations from 0.001 to 100 U/mL in PBS or in diluted fetal bovine serum (1000×) in PBS. Compared to the polyacrylamide (PAAm) MIP from conventional free-radical polymerization, the ATRP-based MIP extended the biosensor's dynamic linear range 10-fold, improving low concentration detection, and enhanced the signal reproducibility across units. The biosensor demonstrated good sensitivity and selectivity. Overall, the work described confirmed that the process of radical polymerization to build an MIP material influences the detection capacity for the target substance and the reproducibility among different biosensor units. Extending this approach to other cancer biomarkers, the methodology presented could open doors to a new generation of MIP-based biosensors for point-of-care disease diagnosis.

Elevation of cancer antigen 15-3 owing to oncocytic renal neoplasm in a patient without evidence of breast cancer recurrence on follow-up: a case report.

BACKGROUND: Cancer antigen 15-3 is a protein that clinicians commonly measure to monitor outcomes and response to treatment in patients with breast cancer. However, cancer antigen 15-3 can also be elevated in other, benign and malignant conditions. CASE PRESENTATION: A 73-year-old White woman with history of breast cancer presented to her primary care physician with right hip pain, and laboratory testing revealed elevated cancer antigen 15-3. Further workup with radiographic imaging revealed a large mass in her right kidney. The renal mass was subsequently removed, and the cancer antigen 15-3 level returned to normal. CONCLUSIONS: Elevation of cancer antigen 15-3 owing to causes other than breast cancer recurrence can be a potential diagnostic pitfall during a patient's follow-up. It is important for clinicians to be aware of the limitations of cancer markers and to utilize a combination of diagnostic tests for patient evaluation.

Dual-Mode Sensing Platform for Cancer Antigen 15-3 Determination Based on a Silica Nanochannel Array Using Electrochemiluminescence and Electrochemistry.

An electrochemiluminescence-electrochemistry (ECL-EC) dual-mode sensing platform based on a vertically-ordered mesoporous silica films (VMSF) modified electrode was designed here for the sensitive and selective determination of cancer antigen 15-3 (CA 15-3), a specific biomarker of breast cancer. VMSF was assembled through a rapid electrochemically assisted self-assembly (EASA) method and plays a crucial role in signal amplification via a strong electrostatic interaction with the positively charged bifunctional probe Ru(bpy)32+. To construct the biorecognition interface, epoxy functional silane was linked to the surface of VMSF for further covalent immobilization of the antibody. As a benefit from the specific combination of antigen and antibody, a non-conductive immunocomplex layer was formed in the presence of CA 15-3, leading to the hinderance of the mass and electron transfer of the probes. Based on this strategy, the dual-mode determination of CA 15-3 ranging from 0.1 mU/mL to 100 mU/mL with a LOD of 9 µU/mL for ECL mode, and 10 mU/mL to 200 U/mL with a LOD of 5.4 mU/mL for EC mode, was achieved. The proposed immunosensor was successfully employed for the detection of CA 15-3 in human serum without tedious pretreatment.

Impact of Breast Tumor Onset on Blood Count, Carcinoembryonic Antigen, Cancer Antigen 15-3 and Lymphoid Subpopulations Supported by Automatic Classification Approach: A Pilot Study.

BACKGROUND: Recent observations showed that systemic immune changes are detectable in case of breast cancer (BC). In this preliminary study, we investigated routinely measured peripheral blood (PB) parameters for malignant BC cases in comparison to benign breast conditions. Complete blood count, circulating lymphoid subpopulation, and serological carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) levels were considered. METHODS: A total of 127 female patients affected by malignant (n = 77, mean age = 63 years, min = 36, max = 90) BC at diagnosis (naïve patients) or benign breast conditions (n = 50, mean age = 33 years, min = 18, max = 60) were included in this study. For each patient, complete blood count and lymphoid subpopulations (T-helper, T-cytotoxic, B-, NK-, and NKT-cells) analysis on PB samples were performed. Hormonal receptor status, Ki-67 expression, and serological CEA and CA15-3 levels were assessed in the case of patients with malignant BC via statistical analysis. RESULTS: Women with malignant BC disclosed increased circulating T-helper lymphocytes and CD4/CD8 ratio in PB when compared to those affected by benign breast conditions (2.345 vs 1.894, P < .05 Wilcoxon rank-sum test). In the case of malignant BC patients, additive logistic regression method was able to identify malignant BC cases with increased CA15-3 levels (CA15-3 >25 UI/mL) via the hematocrit and neutrophils/lymphocytes ratio values. Moreover, in the case of women with aggressive malignant BC featured by high levels of Ki-67 proliferation marker, an increasing number of correlations were found among blood count parameters and lymphocytes subpopulations by performing a Spearman's correlation analysis. CONCLUSIONS: This preliminary study confirms the ability of malignant BC to determine systemic modifications. The stratification of malignant BC cases according to the Ki-67 proliferation marker highlighted increasing detectable alterations in the periphery of women with aggressive BC. The advent of novel and more sensitive biomarkers, as well as deep immunophenotyping technologies, will provide additional insights for describing the relationship between tumor onset and peripheral alterations.

The Role of Tumor Markers: Carcinoembryonic Antigen and Cancer Antigen 15-3 in Patients With Breast Cancer.

Introduction  Breast cancer is a major cause of mortality among females, worldwide. The present study was intended to evaluate the significance in the management of carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) in patients with breast cancer. Methodology A cohort study was conducted at the Jinnah Postgraduate Medical Center, Karachi, Pakistan from June 2020 to May 2021. All diagnosed cases of breast cancer who underwent surgical excision of tumor were eligible to partake. Patients who had metastatic breast cancer or had a recurrence were excluded. The patient's sociodemographic and clinical data were documented in a predefined pro forma. It included information about the age, sex, weight, as well as serum CEA and CA15-3. The CA15-3 and CEA levels for each patient were assessed by taking a 5ml blood sample and sending it to the laboratory for further workup. preoperatively on the second, seventh, and 28th postoperative days. Results A mean ± SD age of 52.6 ± 8.89 years was reported. Family history of breast cancer was positive in one-fourth of the patients. Nodal metastasis was negative in 114 (46.72%) patients. Three-fourth of patients had Stage II-IV with only a minority diagnosed with Stage I. The mean levels for CA15-3 in women with Stage I cancer was significantly lower on the seventh day and 28th postoperative day, compared to preoperative levels (p = 0.05). Similar associations were seen for stages II and III. Higher CEA levels were significantly associated with stage III breast cancer preoperatively (5.88 ng/ml, p = 0.05) compared to postoperative values. Conclusion The current study revealed that preoperative values of serum CEA and CA15-3 significantly reduced postoperatively. Moreover, patients with advanced cancers had significantly higher levels of both tumor markers than those with less advanced diseases. The current study highlighted the importance of regular assessment of serum CEA and CA15-3 in breast cancer patients. Both these biomarkers are substantially elevated in breast cancer patients, preoperatively. Determining the levels of serum CEA and CA15-3 pre- and postoperatively may determine the prognosis and aid in forming the most optimal patient care regime with respect to the stage and subtype of cancer.

Preoperative Routine Laboratory Markers for Predicting Postoperative Recurrence and Death in Patients with Breast Cancer.

Simple, convenient, and reliable preoperative prognostic indicators are needed to estimate the future risk of recurrences and guide the treatment decisions associated with breast cancer. We evaluated preoperative hematological markers related to recurrence and mortality and investigated independent risk factors for recurrence and mortality in patients after breast cancer surgery. We reviewed electronic medical records of patients with invasive breast cancer diagnosed at our tertiary institution between November 2005 and December 2010 and followed them until 2015. We compared two groups of patients classified according to recurrence or death and identified risk factors for postoperative outcomes. Data from 1783 patients were analyzed ultimately. Cancer antigen (CA) 15-3 and red cell distribution width (RDW) had the highest area under the curve values among several preoperative hematological markers for disease-free survival and overall survival (0.590 and 0.637, respectively). Patients with both preoperative CA 15-3 levels over 11.4 and RDW over 13.5 had a 1.7-fold higher risk of recurrence (hazard ratio (HR): 1.655; 95% confidence interval (CI): 1.154-2.374; p = 0.007) and mortality (HR: 1.723; 95% CI: 1.098-2.704; p = 0.019). In conclusion, relatively high preoperative RDW (>13.5) and CA 15-3 levels (>11.4) had the highest predictive power for mortality and recurrence, respectively. When RDW and CA 15-3 exceeded the cut-off value, the risk of recurrence and death also increased approximately 1.7 times.

Serum biomarker CA 15-3 as predictor of response to antifibrotic treatment and survival in idiopathic pulmonary fibrosis.

Aim: Cancer antigen 15-3 (CA 15-3) is a baseline biomarker in idiopathic pulmonary fibrosis (IPF), but its value during follow-up is unknown. Materials and methods: Associations between serum CA 15-3 and pulmonary function tests during 1-year follow-up were evaluated by a mixed model in 132 IPF treated with pirfenidone or nintedanib. Results: Increased baseline (median: 56 kU/l) and follow-up CA 15-3 levels were inversely associated with forced vital capacity and diffusing capacity of the lung for carbon monoxide (estimates respectively: -5.21 and -4.69; p < 0.001). Baseline and 6-month CA 15-3 above 58.5 (hazard ratio: 1.67; p = 0.031) and 50.5 kU/l (hazard ratio: 2.99; p < 0.001), respectively, showed impaired survival compared with lower levels. Conclusion: CA 15-3 is associated with pulmonary function test during follow-up in IPF on antifibrotic treatment. Higher (follow-up) values are related with poor survival. Therefore, CA 15-3 is a promising follow-up biomarker in IPF.

Correlation between salivary and serum CA15-3 concentrations in patients with breast cancer.

The early detection of breast cancer enables the use of less aggressive treatment and increases patient survival. The transmembrane glycoprotein mucin 1, which is also known as cancer antigen 15-3 (CA15-3), is aberrantly glycosylated and overexpressed in a variety of epithelial cancers, and serves a crucial role in the progression of the disease. CA15-3 is currently used as a marker of breast cancer. In the present study, CA15-3 concentrations in saliva and blood of patients with breast cancer were evaluated to test new assays to detect salivary CA15-3 in addition to ELISA and its diagnostic value. To the best of our knowledge, there are no previous reports of the use of chemiluminescence assay (CLIA) and electrochemiluminescence assay (ECLIA) in saliva. Saliva and blood were collected on the same day from patients with breast cancer (n=26) and healthy controls (n=28). For each subject, the level of serum CA15-3 was measured using ECLIA, and the level of salivary CA15-3 was measured using ECLIA, CLIA and enzyme-linked immunosorbent assay (ELISA). ELISA and CLIA were able to detect CA15-3 in saliva; however, ECLIA could not detect salivary CA15-3. There was no significant difference between the mean serum and salivary CA15-3 levels in patients with breast cancer or healthy controls. The levels of CA15-3 were highest for luminal breast cancer subtypes and stage IV cases. A moderate correlation was observed between salivary and serum CA15-3 levels as measured by ELISA in breast cancer patients (r=0.56; P=0.0047). The results demonstrated that ECLIA was not a good method to detect salivary CA15-3, although it is the gold standard for detecting serum CA15-3. The presence of CA15-3 in saliva was confirmed, and this will be useful in future research. Further investigations are necessary to confirm the ability to detect salivary CA15-3 and its correlation with serum CA15-3.

The Distribution of Circulating Tumor Cells Is Different in Metastatic Lobular Compared to Ductal Carcinoma of the Breast-Long-Term Prognostic Significance.

BACKGROUND: Invasive lobular carcinoma (ILC) has distinguishing features when compared to invasive ductal carcinoma of no special type (NST). In this study, we explored the distributional and prognostic characteristics of circulating tumor cells (CTCs) in metastatic ILC and NST. MATERIALS AND METHODS: Patients were included in an observational trial (ClinicalTrials.gov NCT01322893) with ILC (n = 28) and NST (n = 111). CTC count (number/7.5 mL blood) was evaluated with serial sampling (CellSearch). The primary endpoint was progression-free survival (PFS). RESULTS: The CTC counts were higher in ILC (median 70) than in NST cases (median 2) at baseline (p < 0.001). The evidence for ≥5 CTCs as a prognostic factor for PFS in ILC was weak, but stronger with higher cut-offs (CTC ≥ 20: hazard ratio (HR) 3.0, p = 0.01) (CTC ≥ 80: HR 3.6, p = 0.004). In NST, however, the prognostic effect of CTCs ≥5 was strong. Decline in CTC count from baseline to three months was associated with improved prognosis in ILC and NST. CONCLUSIONS: The number of CTCs is higher in ILC than in NST, implying that a higher CTC cut-off could be considered for ILC when applying the CellSearch technique.

Change in Serum Biomarker CA 15-3 as an Early Predictor of Response to Treatment and Survival in Hypersensitivity Pneumonitis.

BACKGROUND: Hypersensitivity pneumonitis (HP) is an interstitial lung disease with a heterogeneous course of disease and treatment response. Cancer antigen 15-3 (CA 15-3), part of mucin 1, is believed to reflect epithelial cell injury and lung permeability and could be a potential biomarker for treatment response in HP. OBJECTIVE: To assess the value of CA 15-3 as a predictive biomarker in non-fibrotic and fibrotic HP during immunosuppressive therapy. DESIGN: Serum levels of CA 15-3 and pulmonary function tests (PFTs) were retrospectively retrieved from 48 HP patients treated with prednisone or cyclophosphamide at initiation of therapy (baseline), after 3 and 6 months. Pearson's correlation coefficient was computed to assess correlations between change in serum levels and PFT. Survival was evaluated using Kaplan-Meier curves. RESULTS: After 6 months of immunosuppressive therapy CA 15-3 levels decreased significantly compared to baseline (p = 0.001). Change in CA 15-3 after 6 months correlated with FVC change (r = - 0.469; p = 0.001). Correlations with FVC change were observed in prednisone-treated HP (r = - 0.514; p = 0.005) and fibrotic HP (r = - 0.417; p = 0.007). Three-month CA 15-3 change correlated with 6-month FVC change (r = - 0.599; p < 0.001). CA 15-3 declines of at least 7.9% after 6 months were associated with increased survival compared to minor CA 15-3 changes (HR 0.34; p = 0.020). CONCLUSION: Serum CA 15-3 correlates with PFT during 6 months of immunosuppressive therapy in HP. Interestingly, early CA 15-3 changes could predict future PFT. Furthermore, a decrease in CA 15-3 is related to longer survival. Therefore, serum CA 15-3 is a promising biomarker for implementation in HP care.

Dosagem sérica do marcador tumoral CA 15. 3 em cadelas portadoras de neoplasias mamárias pelo método de eletroquimioluminescência / Serum dosage of the tumor marker Ca 15. 3 in bitches presenting mammary neoplasia with the chemiluminescence method

The objective of the present study was to analyze the serum levels of the tumor marker Ca15.3 in healthy bitches and those with mammary neoplasms, correlating results with tumor type, clinical staging, time until presentation, and presence of ulceration and vascularization. For the study, 30 bitches with mammary tumors and 30 healthy bitches (control group) were selected. Histopathology was performed for identification of tumor type, and blood was collected for measurement of serum concentration of the marker via the chemiluminescence method using a commercial kit. A higher frequency of malignant neoplasms was observed (76.7%), with a higher quantity of carcinoma in mixed tumor (26.7%). Regarding serum concentration of the marker Ca15.3, there was no difference in serum values when comparing the means from bitches with neoplasia and healthy bitches, nor when comparing the other characteristics. The majority of results for serum concentration of Ca15.3, whether in bitches with neoplasia or in healthy bitches, was zero. It is concluded that the measurement of the marker Ca15.3 using the chemiluminescence method and commercial kits for humans did not offer significant results that would make this method or this marker a useful tool for patient monitoring and evaluation of the prognosis of bitches with mammary neoplasms.(AU)

Determination of the prognostic value of preoperative CA15-3 and CEA in predicting the prognosis of young patients with breast cancer.

To the best of our knowledge, no previous study has investigated the association of carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) with the prognosis for young patients (≤40 years) with breast cancer. In the present study, preoperative CEA and CA15-3 serum levels were evaluated in the prediction of the prognosis for young patients with breast cancer. In total, 699 patients were recruited, for which the CEA and CA15-3 serum levels had been measured prior to surgery via a blood sample. The optimal cut-off high and low values were determined using receiver operating characteristic curve analysis and Youden's index. The value of CEA and CA15-3 in predicting overall survival (OS) and disease-free survival (DFS) were measured using univariate and multivariate Cox's regression analyses. The cut-off values were 3.38 ng/ml and 12.32 U/ml for CEA and CA15-3, respectively. It was identified that CEA, but not CA15-3, was a predictor for the prognosis of the young patients with breast cancer. Multivariate analysis confirmed that CEA, but not CA15-3, was an independent prognostic marker for all young patients with breast cancer. In total, 623 young patients exhibited decreased levels of CEA; in these patients, CA15-3 with a cut-off value of 12.48 U/ml was an independent prognostic factor for OS and DFS. Preoperative serum CEA may thus serve as an independent predictor of poor prognosis for young patients with breast cancer. However, for low-risk patients with decreased CEA levels, serum CA15-3 may supplement the prediction of overall prognosis.

Simplified approach for in-vitro production and purification of cell derived Cancer Antigen 15-3.

Cancer antigen 15-3 (CA15-3) is a key biomarker, currently used for understanding the onset and prognosis of breast cancer. In present investigation, CA15-3 has been purified from the culture supernatant of breast cancer T47-D cell line with 76% yield and 3350 fold purification. Isolated CA15-3 was analyzed by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), immunoblotting (western blotting), chemiluminescence immunoassay (CLIA) and Fourier-transform infrared spectroscopy (FTIR). CA15-3 is a monomeric protein with an apparent molecular mass in between ∼250-350kDa. The FTIR spectroscopy revealed similar profiles of T47-D derived CA15-3 and commercially available CA15-3 protein. With the easy availability of T47-D cell line and a simple purification approach described here will support for the large scale production of CA15-3 to be used for various clinical and diagnostic applications.

Cancer antigen 15-3, platelet distribution width, and fibrinogen in combination to distinguish breast cancer from benign breast disease in non-conclusive mammography patients.

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females. However, mammographic diagnosis is sometimes non-conclusive with a Breast imaging Reporting and Data System (Bi-RaDS) result of 0. Cancer antigen 15-3 (CA15-3) is the most widely used serum tumor marker for breast cancer screening. Platelet distribution width (PDW) is an early indicator of platelet activation. Fibrinogen contributed to angiogenesis and distant metastasis. The aim of this study was to investigate the ability of CA15-3, PDW, and fibrinogen individually or in combination, to distinguish breast cancer from benign breast disease. 200 consecutive patients with breast cancer and 187 patients with benign breast disease were included in this retrospective study. Patients' characteristics and hematologic tests data at initial diagnosis were collected. The benefit of adding PDW and fibrinogen to a model with only CA15-3 was evaluated as an increased in the area under the curve (AUC) obtained by receiver operating curve (ROC). CA15-3, PDW and fibrinogen are higher in breast cancer patients than in patients with benign breast disease. Single biomarkers had AUC values ranging from 0.687 for fibrinogen to 0.810 for CA15-3. In addition, the combination of PDW, CA15-3, and fibrinogen increased the AUC to 0.900 (0.866-0.928) (p<0.0001), significantly higher than those of any single marker. In conclusion, the combined use of CA15-3, PDW and fibrinogen may be clinically useful in discriminating between breast cancer and benign breast disease in non-conclusive mammography patients.

Diagnostic value of epidermal growth factor, cancer antigen 125, and cancer antigen 15-3 in bronchoalveolar lavage fluid of lung cancer.

AIM: In the present study, we assessed the diagnostic value of epidermal growth factor (egf) and cancer antigens 125 (ca125) and 15-3 (ca15-3) in bronchoalveolar lavage fluid (balf) of lung cancer from 79 enrolled patients with suspected lung cancer. METHODS: All patients underwent fibrescopic examination, during which balf samples were collected. Levels of egf, ca125, and ca15-3 were determined in balf using commercially available test kits. RESULTS: The results showed that levels of egf in balf were significantly higher in patients with lung cancer than in patients with benign diseases (p < 0.01); no significant differences for ca125 (p = 0.67) or ca15-3 (p = 0.43) in balf were observed between the lung cancer patients and the non-cancer control subjects. With a cut-off value of 27.22 pg/mL, egf showed a sensitivity of 63.6% and a specificity of 65.7% in predicting the malignant nature of pulmonary disease. CONCLUSIONS: The study findings suggest that levels of egf are significantly increased in balf from patients with lung cancer than in balf from patients with benign disease. Detection of the level of egf in balf is proposed as a noninvasive test to identify patients at high risk for lung cancer.

Diagnostic Value of Neuron-Specific Enolase (NSE) and Cancer Antigen 15-3 (CA 15-3) in the Diagnosis of Pleural Effusions

Introduction: Pleural effusion diagnosis plays an important role in determining treatment strategies. The aim of this study was to determine the diagnostic capacity of tumor markers CA 15-3 and NSE solely or in combination in differentiating the nature of pleural fluid. Methods and Materials: In this cross-sectional study we evaluated 93 patients with pleural effusions (44 malignant and 49 benign). NSE and CA 15-3 serum and pleural levels were measured simultaneously using immunoenzyme assay kits. Diagnosis was established on the basis of cytological study. Results: Sensitivity and specificity of CA 15-3 serum and pleural level measurement were 70.4%, 49.0%, and 79.5% and 49.0%, respectively. Serum NSE levels had 75.0% sensitivity and 69.4% specificity while the respective pleural figures were 75.0% and 73.5%. The combination of NSE and CA 15-3 serum and pleural levels had the highest sensitivity (93.2%), although combined serum levels had the lowest sensitivity (47.7%). With an accuracy of 74.2%, pleural levels of NSE had the highest diagnostic potential. Conclusion: Measuring NSE and CA 15-3 tumor markers is a suitable approach to distinguish the nature of pleural effusions, with NSE pleural levels demonstrating the highest diagnostic accuracy.

A new marker for breast cancer diagnosis, human epididymis protein 4: A preliminary study.

Breast cancer is the most frequently diagnosed cancer type in women. Tumor markers have been widely used for assessing the treatment response and early diagnosis of recurrence. Human epididymis protein 4 (HE4) is expressed in ductal carcinoma of the breast tissue; however, its serum levels and their diagnostic and prognostic potential in breast cancer have not been investigated, which was therefore the aim of the present study. The serum levels of HE4 were determined in 36 breast cancer patients, 11 ovarian cancer patients and 16 healthy volunteers. The association between clinicopathological characteristics of breast cancer and serum HE4 levels was investigated. A significant difference in the median serum levels of HE4 was identified between breast cancer patients, ovarian cancer patients and healthy volunteers (P=0.013). The cutoff value for the prediction of breast cancer was determined at >13.24 pmol/l for HE4, with a sensitivity of 61.11%, specificity of 68.75%, positive predictive value of 81.48%, negative predictive value of 44.0% and accuracy of 63.46%. Furthermore, a positive correlation between the serum levels of HE4 and cancer antigen 15-3 was determined (r=0.399, P=0.026). To the best of our knowledge, the present study was the first to determine the diagnostic value of serum HE4 for breast cancer. A significant elevation of serum HE4 levels in patients with breast cancer compared with that in healthy controls was identified. HE4 may serve as a novel biomarker for the diagnosis of breast cancer.

A cross-sectional study of tumor markers during normal and high-risk pregnancies.

OBJECTIVE: To determine tumor marker concentrations during normal and high-risk pregnancies. METHODS: The present cross-sectional study included women attending the gynecology outpatient department at All India Institute of Medical Sciences, New Delhi, India, between November 1, 2012 and March 31, 2013. Their serum was assayed for carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), and cancer antigen 15-3 (CA15-3). RESULTS: A total of 251 pregnant women and 31 nonpregnant women were included. Median CEA value was lower among pregnant women than among nonpregnant women (1.2µg/L vs 1.4µg/L; P=0.006), whereas that of CA15-3 was higher (16.7U/mL vs 12.3U/mL; P=0.03). CA19-9 concentration was higher among pregnant women aged 25-29years (7.0U/mL) or 30-34years (7.2U/mL) than among those aged 20-24years (4.2U/mL; P=0.01 for both). The CA15-3 level was increased during the second (13.0U/mL) and third (60.5U/mL) trimesters compared with the first trimester (9.5U/mL) (P≤0.01 for both comparisons). It was also raised in high-risk pregnancies (33.7U/mL), specifically pregnancies complicated by gestational diabetes mellitus (39.7U/mL), intrahepatic cholestasis of pregnancy (64.3U/mL), or heart disease (54.0U/mL) (P<0.05 for all). CONCLUSION: CA15-3 concentrations rise during pregnancy, but whether this increase can be attributed to physiological changes in breast tissue needs to be investigated further.