The Usefulness of the Combination of Free CA 15.3 and CA 15.3-IGM Complexes for Breast Cancer Diagnosis

2009 ◽  
Vol 24 (3) ◽  
pp. 193-193
Author(s):  
Elisa Bucca ◽  
Luca Beneduce ◽  
Antonette E. Leon ◽  
Aline S.C. Fabricio ◽  
Silvia Michilin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Immune Complexes ◽  
Serum Levels ◽  
Diagnostic Value ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Serum Samples ◽  
Ca 15.3 ◽  
Cutoff Values

Background Several studies have shown that the main circulating biomarkers of liver and colorectal cancer can be detected in the bloodstream and are also associated with immunoglobulin M to form stable complexes. These immune complexes show increased capacity of discrimination between cancer patients and healthy controls if combined with the free biomarker form. Within the context of the Project FIRB 2003 - Nanosized Cancer Polymarker Biochip - we wanted to investigate if IgM complexes have importance also in breast cancer. We focused our study on the immune complexes between IgM and CA 15.3 because free CA 15.3 is the most commonly used breast cancer biomarker in clinical practice. However, this biomarker alone lacks satisfactory sensitivity especially in early cancer detection. Aim The aim of our study was to assess the occurrence of immune complexes between CA 15.3 and IgM in sera from patients with primary breast cancer and in sera from healthy controls to evaluate its putative diagnostic value compared with the diagnostic value of free CA 15.3. Methods A total of 130 serum samples were obtained from 56 healthy women (mean age±SD, 45±8.23 years) and 74 women with stage l and II breast cancer (mean age±SD, 59±13.6 years) before any treatment, either surgical or chemo-therapeutic. Serum samples were collected, aliquoted and stored at-80°C in the centralized biobank of the project according to very stringent standard operating procedures (SOPs) distributed by the coordinating unit. To evaluate the presence of CA 15.3-lgM immune complexes, we developed and validated a novel enzyme-linked immunosorbent assay (ELISA) with a polyclonal rabbit anti-human CA 15.3 antibody (Abcam) as the catcher antibody. CA 15.3-lgM was detected with peroxidase-conjugated anti-human IgM and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and hydrogen peroxide as substrate (Sigma Aldrich, Italy). The levels of CA 15.3-lgM were expressed in arbitrary units per mL (AU/mL) by interpolation on a calibration curve obtained by serial dilution of a reference calibrator purified by gel filtration chromatography from a pool of serum samples with high levels of CA 15.3-lgM. Serum levels of free CA 15.3 were assessed in parallel on each sample using an automated immunoassay system (ADVIA Centaur-Siemens Diagnostics) and expressed in U/mL. Results To discriminate between cancer patients and healthy controls, we used as cutoff values 31.5 U/mL for free CA 15.3 (corresponding to the cutoff used in the clinical routine) and 794 AU/mL for CA 15.3-lgM (representing the 95th percentile of the distribution of serum levels of CA 15.3-lgM in healthy controls). By using these cutoff values, we obtained a sensitivity of 1 0% (7/74 cases) and a specificity of 95% (53/56 controls) for CA 15.3-lgM. The sensitivity and specificity of free CA15.3 were 7% (5/74 cases) and 1 00% (56/56 controls), respectively. Interestingly, the serum levels of the two biomarkers did not overlap, so their combination at 95% specificity identified 12/74 cases (16.2%). When we took a cutoff of 22 U/ mL for free CA15.3 (the 95th percentile of its distribution in healthy controls), we calculated a sensitivity of 26% (1 9/74 cases) and a specificity of 95% (53/56 controls); its combination with CA 15.3-lgM had a sensitivity of 34% (25/74 cases) and a specificity of 90% (50/56 controls). Conclusions These results demonstrate for the first time the presence of CA 15.3-lgM in the bloodstream of patients with breast cancer. In addition, our data suggest that CA 15.3-lgM is a complementary serological marker to free CA 15.3 and the combination of these biomarkers could improve the diagnosis of breast cancer.

Serum chemokine CXCL7 activity after resection of breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22182-e22182
Author(s):  
Mary Ann Kosir ◽  
Donghong Ju
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Serum Levels ◽  
Partial Mastectomy ◽  
Enzyme Linked Immunosorbent Assay ◽  
Normal Donor ◽  
Breast Cancer Patients ◽  
Serum Samples ◽  
Preoperative Serum ◽  
Er Positive

e22182 Background: The chemokine CXCL7 is associated with tumor migration, invasion and angiogenesis and is a ligand for CXCR2. The purpose of the study is to measure changes in serum chemokine CXCL7 from resectable breast cancer patients between preoperative and postoperative blood samples. Methods: With IRB approval, we prospectively collected serum samples from patients undergoing breast cancer surgery immediately preoperatively and at least one week postoperatively. Serum CXCL7 protein concentrations were measured by enzyme-linked immunosorbent assay (ELISA) using human CXCL7/NAP-2 Duo set ELISA Development System (R and D Systems, Minneapolis, MN) according to manufacturer’s instructions. Measurements were performed in duplicate with three separate experiments. Results were analyzed using unpaired and paired Student’s t-Test. Demographic and clinical information were collected. Normal donor samples were from ProteoGenex. Results: Twenty-three matched serum samples were analyzed. The mean age was 52 years (range 36-67), 65.2% were African American, 56.5% underwent partial mastectomy. There were 5 in Stage I, 9 in Stage II, 2 in Stage III, and 7 in Stage 0. Only 4 of 16 with invasive cancer had nodal disease, 11 were ER positive, 6 were triple negative, and 5 of 7 with DCIS were ER positive. Matched serum samples showed greater CXCL7 serum levels in preoperative samples when compared to normal donor samples (9.10 ±0.45 vs 8.10 ± 0.22 ug/ml; mean±sem, p<0.05). The CXCL7 serum levels were significantly decreased in postoperative serum as compared to preoperative serum (8.40 ± 0.47 vs 9.10 ± 0.45 ug/ml; mean±sem, p<0.05) reaching normal donor serum levels. When individual matched pairs of serum were analyzed, 16 showed decrease in postoperative CXCL7 levels compared to preoperative. Conclusions: The chemokine CXCL7 found in serum is increased in breast cancer patients compared to normal donors, and significantly decreases postoperatively to normal levels. This supports translational research of the role of CXCL7 in breast cancer.

Overexpression of microRNA-21 in the Serum of Breast Cancer Patients

MicroRNA ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 58-63
Author(s):  
Batool Savari ◽  
Sohrab Boozarpour ◽  
Maryam Tahmasebi-Birgani ◽  
Hossein Sabouri ◽  
Seyed Mohammad Hosseini
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Tumor Resection ◽  
Tumor Grade ◽  
Healthy Controls ◽  
Breast Cancer Patients ◽  
Serum Samples ◽  
Post Surgery ◽  
Polymerase Chain

Background: Breast cancer is the most common cancer diagnosed in women worldwide. So it seems that there's a good chance of recovery if it's detected in its early stages even before the appearances of symptoms. Recent studies have shown that miRNAs play an important role during cancer progression. These transcripts can be tracked in liquid samples to reveal if cancer exists, for earlier treatment. MicroRNA-21 (miR-21) has been shown to be a key regulator of carcinogenesis, and breast tumor is no exception. Objective: The present study was aimed to track the miR-21 expression level in serum of the breast cancer patients in comparison with that of normal counterparts. Methods: Comparative real-time polymerase chain reaction was applied to determine the levels of expression of miR-21 in the serum samples of 57 participants from which, 42 were the patients with breast cancer including pre-surgery patients (n = 30) and post-surgery patients (n = 12), and the others were the healthy controls (n = 15). Results: MiR-21 was significantly over expressed in the serum of breast cancer patients as compared with healthy controls (P = 0.002). A significant decrease was also observed following tumor resection (P < 0.0001). Moreover, it was found that miR-21 overexpression level was significantly associated with tumor grade (P = 0.004). Conclusion: These findings suggest that miR-21 has the potential to be used as a novel breast cancer biomarker for early detection and prognosis, although further experiments are needed.

scholarly journals Clinical Significance of Annexin A2 Expression in Breast Cancer Patients

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 2
Author(s):  
Lee D. Gibbs ◽  
Kelsey Mansheim ◽  
Sayantan Maji ◽  
Rajesh Nandy ◽  
Cheryl M. Lewis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Clinical Significance ◽  
Cell Lines ◽  
Breast Cancer Subtypes ◽  
Enzyme Linked Immunosorbent Assay ◽  
Breast Cancer Patients ◽  
Serum Samples ◽  
Cancer Subtypes ◽  
Tumor Tissues

Increasing evidence suggests that AnxA2 contributes to invasion and metastasis of breast cancer. However, the clinical significance of AnxA2 expression in breast cancer has not been reported. The expression of AnxA2 in cell lines, tumor tissues, and serum samples of breast cancer patients were analyzed by immunoblotting, immunohistochemistry, and enzyme-linked immunosorbent assay, respectively. We found that AnxA2 was significantly upregulated in tumor tissues and serum samples of breast cancer patients compared with normal controls. The high expression of serum AnxA2 was significantly associated with tumor grades and poor survival of the breast cancer patients. Based on molecular subtypes, AnxA2 expression was significantly elevated in tumor tissues and serum samples of triple-negative breast cancer (TNBC) patients compared with other breast cancer subtypes. Our analyses on breast cancer cell lines demonstrated that secretion of AnxA2 is associated with its tyrosine 23 (Tyr23) phosphorylation in cells. The expression of non-phosphomimetic mutant of AnxA2 in HCC1395 cells inhibits its secretion from cells compared to wild-type AnxA2, which further suggest that Tyr23 phosphorylation is a critical step for AnxA2 secretion from TNBC cells. Our analysis of AnxA2 phosphorylation in clinical samples further confirmed that the phosphorylation of AnxA2 at Tyr23 was high in tumor tissues of TNBC patients compared to matched adjacent non-tumorigenic breast tissues. Furthermore, we observed that the diagnostic value of serum AnxA2 was significantly high in TNBC compared with other breast cancer subtypes. These findings suggest that serum AnxA2 concentration could be a potential diagnostic biomarker for TNBC patients.

Exploring The Clinical Significance of Serum Angiopoietin-2 In Breast Cancer Patients

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Abeer I Abd Elmagid ◽  
Hala Abdel Al ◽  
Wessam El Sayed Saad ◽  
Seham Kamal Mohamed
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Serum Levels ◽  
Tnm Staging ◽  
Control Group ◽  
Healthy Controls ◽  
Breast Cancer Patients ◽  
Female Patients ◽  
Significant Difference ◽  
Angiopoietin 2

Abstract Background Breast cancer is the most common cancer among women and one of the most important causes of death among them.Angiogenesis is an important step for primary tumor growth, invasiveness, and metastases. Angiopoietins are well-recognized endothelial growth factors that are involved in angiogenesis associated with tumors. Aim To explore the diagnostic significance of serum angiopoietin-2 (Ang-2) in breast cancer and to evaluate its prognostic efficacy through studying the degree of its association with the TNM staging of the disease. Patients and Methods This study was conducted on (35) Egyptian female patients who were diagnosed as breast cancer according to histopathological examination of breast biopsy (Group 1, Breast Cancer Patients) and (25) female patients with benign breast diseases (Group II, Pathological Control Patients), in addition to (20) age - matched apparently healthy, free mammogram, females serving as healthy controls (Group III, Healthy Controls). For all participants, measurement of serum Ang-2 was done using enzyme linked immunosorbent assay (ELISA) technique. Results A highly significant increased levels of Ang-2 was observed in breast cancer patients when compared to healthy control group (Z = 4.95, p &lt; 0.01). However, no significant difference was observed in Ang-2 levels between breast cancer patients group and pathological control group (Z = 3.37, p &gt; 0.05). No significant difference was detected in Ang-2 levels in relation to TNM stage and histological grade. No significant correlation was found between Ang-2 levels and serum levels of CA15-3, hormone receptors, HER2/new receptor status (p &gt; 0.05, respectively). Conclusion This study revealed that Ang-2 serum levels were significantly increased in patient with breast cancer compared with healthy controls, indicating that high Ang-2 level is a promising non invasive biomarker for breast cancer diagnosis. However, no significant difference of Ang-2 levels was detected in relation of breast TNM staging in the population studied.

scholarly journals Differential Expression of Serum Exosomal miRNAs in Breast Cancer Patients and Healthy Controls

2021 ◽  
Author(s):  
Rahim Asgari ◽  
Jafar Rezaie
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Circulatory System ◽  
Health Concern ◽  
Healthy Controls ◽  
Flow Cytometry Analysis ◽  
Breast Cancer Patients ◽  
Serum Samples ◽  
Exosomal Mirnas ◽  
And Control

Purpose: Breast cancer has become as a serious public health concern worldwide. Breast cancer cells release exosomes into the circulatory system, which are easily accessible for further analysis like cancer diagnosis. In this study, we aimed to investigate expression of circulating exosomal miRNAs (miRs) in the serum of individuals with breast cancer and healthy controls. Methods: Exosomes were collected from serum samples using a commercial kit and characterized by scanning electron microscopy (SEM) and flow cytometry analysis. Expression of miRs such as miR-21, miR-155, miR-182, miR-373, and miR-126 were evaluated by real-time PCR. Results: The result showed that the expression level of exosomal miR-21, miR-155, miR-182, and miR-373 in the serum of breast cancer patients was higher than of those controls (P<0.05). However, expression of miR-126 did not change between breast cancer and control individuals (P>0.05). Conclusion: Our results showed a different miRs expression pattern between breast cancer and healthy samples, supposing potential biomarkers for breast cancer. Further studies focusing on these miRs are required to confirm our findings.

CA 549 and SP2 in postoperative breast cancer patients. Comparison with CA 15.3, CEA and TPA

1995 ◽  
Vol 10 (2) ◽  
pp. 94-99 ◽  
Author(s):  
M. Torres ◽  
C. Pacheco ◽  
A. Valverde ◽  
A.C. Rebollo ◽  
A. Moral ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Statistical Analysis ◽  
Cancer Patients ◽  
Blood Donors ◽  
Serum Levels ◽  
Breast Cancer Patients ◽  
Benign Diseases ◽  
Ca 15.3 ◽  
Cancer Group ◽  
Breast Cancer Group

The levels of CA 549 and SP2 were measured in 430 subjects: 100 healthy blood donors, 130 patients with benign diseases and 200 postoperative breast cancer patients. In the latter group, the serum levels of CA 15.3, CEA and TPA were also measured. The Kolmogorov-Smirnov, Mann Whitney and McNemar tests were used for statistical analysis. The upper normal limits were established on the basis of the values obtained in the healthy blood donors group, the benign diseases group and R.O.C. analysis of the breast cancer group. They were: CA 549 = 13 U/ml, SP2 = 14 U/ml, CA 15.3 = 35 U/ml, CEA = 5 ng/ml and TPA = 110 U/ml. The sensitivity, specificity and accuracy in the breast cancer group were, respectively: CA 549 = 78.1%, 97.1% and 88%; SP2 = 21.9%, 90.4% and 57.5%; CEA = 66.7%, 95.2% and 81.5%; CA 15.3 = 80.2%, 98.1% and 89.5%, and TPA = 73.9%, 78.8% and 76.5%. Statistical analysis showed significant differences only between CA 15.3, the marker which gave the best results, and SP2 (p<0.001). There were no significant differences with the association of two or three tumor markers.

scholarly journals Secreted Frizzled-Related Protein 2 Is Associated with Disease Progression and Poor Prognosis in Breast Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Chumei Huang ◽  
Zhuangjian Ye ◽  
Jianxin Wan ◽  
Jianbo Liang ◽  
Min Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Poor Prognosis ◽  
Cancer Drug ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Related Protein ◽  
Breast Cancer Patients ◽  
Kaplan Meier ◽  
Potential Biomarker

Purpose. Secreted frizzled-related protein 2 (sFRP2) is a secreted protein associated with cancer drug resistance and metastasis. However, few studies have reported serum sFRP2 levels in breast cancer. We evaluated serum sFRP2 as a potential biomarker for breast cancer. Methods. Serum sFRP2 concentrations were detected in 274 breast cancer patients along with 147 normal healthy controls by enzyme-linked immunosorbent assay (ELISA). Diagnostic significance was evaluated by area under the curve (AUC) analysis and the Youden index. Prognostic significance was determined by Kaplan-Meier survival method and univariate and multivariate Cox proportional hazard regression model analyses. Results. Serum sFRP2 was elevated in breast cancer patients compared to normal healthy controls (P<0.001). The sensitivity of sFRP2 in diagnosing breast cancer was 76.9% at a specificity of 76.6%. Elevated serum sFRP2 levels are associated with primary tumor size, TNM stage, and lymph node metastases. The Kaplan-Meier curves showed a significant association of serum sFRP2 with progression-free survival. The multivariate Cox analysis confirmed that high serum sFRP2 was an independent prognostic factor for poor prognosis (HR=3.89, 95% CI=1.95-7.68, P=0.001). Conclusions. In conclusion, serum sFRP2 may serve as a potential biomarker for breast cancer diagnosis and prognostic evaluation.

Prognostic value of circulating Bcl-2 and anti-p53 antibodies in patients with breast cancer: A long term follow-up (17.5 years)

2020 ◽  
pp. 1-10
Author(s):  
Maja Sirotković-Skerlev ◽  
Natalija Dedić Plavetić ◽  
Filip Sedlić ◽  
Sanja Kusačić Kuna ◽  
Damir Vrbanec ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Serum Levels ◽  
High Serum ◽  
Clinicopathological Parameters ◽  
Enzyme Linked Immunosorbent Assay ◽  
Breast Cancer Patients ◽  
P53 Antibodies

BACKGROUND: Apoptosis inhibition is a major tumorigenic factor. Bcl-2 dysregulation and TP53 mutation status, which may correlate with autoantibody generation, contribute to impaired apoptosis. OBJECTIVE: This study aimed to investigate the prognostic value of circulating Bcl-2 and anti-p53 antibodies (p53Abs) in a 17.5-year follow-up of breast cancer patients. We also analyzed the correlations of Bcl-2 and p53Abs with various clinicopathological parameters in order to assess their impact on tumor aggressiveness. METHODS: Serum Bcl-2 and p53Abs levels were analyzed by the enzyme-linked immunosorbent assay (ELISA) in 82 patients with invasive breast cancer and twenty individuals without malignancy. RESULTS: Serum Bcl-2 and p53Abs levels in breast cancer patients were significantly higher than those in controls. Patients with high levels of Bcl-2 (cut-off 200 U/ml) had a poorer prognosis (17.5-year survival) than those with lower Bcl-2 values. In combined analysis the subgroup of patients with elevated p53Abs (cut-off 15 U/ml) and elevated Bcl-2 (cut-offs 124 U/ml and 200 U/ml) had the worse prognosis in 17.5-year survival. In correlation analysis p53Abs and Bcl-2 were associated with unfavorable clinicopathological parameters. CONCLUSIONS: Our results suggest that breast cancer patients with high serum levels of p53Abs and Bcl-2 present an especially unfavorable group in a long follow-up.

Study of serum tumor markers CEA, CA 15.3 and CA 27.29 as diagnostic parameters in patients with breast carcinoma

1995 ◽  
Vol 10 (1) ◽  
pp. 24-29 ◽  
Author(s):  
L. Rodríguez De Paterna ◽  
F. Arnaiz ◽  
J. Estenoz ◽  
B. Ortuño ◽  
E. Lanzós
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Tumor Markers ◽  
Serum Levels ◽  
Breast Diseases ◽  
Breast Cancer Patients ◽  
Ca 15.3 ◽  
Combined Use ◽  
Malignant Breast

Serum levels of CEA, CA 15.3 and CA 27.29 were measured during the follow-up of 499 breast cancer patients. Studies included three different groups of women: 82 blood donors free of disease, 42 patients with non-malignant breast diseases and 499 breast cancer patients. After the determinaion of cut-off values, serum levels of tumor markers did not show significant elevations in benign breast diseases. On the basis of our results CA 15.3 (sensitivity = 57%; accuracy = 87%) was the most effective marker, CA 27.29 (sensitivity = 62%; accuracy = 83%) was the most sensitive and CEA (sensitivity = 45%; accuracy = 81%) was the least sensitive and effective marker. The combined use of markers was evaluated by step-wise logistic regression analysis. The regression coefficients showed that CA 15.3 (coeff. = 2.97) and CA 27.29 (coeff. = 1.46) were suitable for the detection of possible metastases during follow-up. Finally, we studied the relationship between pT, pN, pM and circulating levels of CA 15.3 and CA 27.29.

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