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Breast Cancer : Basic and Clinical... 2019This study determines the co-expression of mammaglobin-A, vascular endothelial growth factor receptor-3 (VEGFR3) and Ki67 by immunohistochemistry (IHC) in tissue samples...
BACKGROUND/METHODS
This study determines the co-expression of mammaglobin-A, vascular endothelial growth factor receptor-3 (VEGFR3) and Ki67 by immunohistochemistry (IHC) in tissue samples from 80 patients undergoing breast surgery (cancer or benign disease). The tissue expression was compared with the tumour histopathology and Kaplan Meier 5-year survival analysis was performed.
RESULTS
Positive breast tissue expression was observed in 53% samples for mammaglobin, 41% Ki67 and 65% VEGFR3 with a significant positive correlation between Ki67 and VEGFR3 co-expression. Ki67 and VEGFR3 expression correlated with the breast tumour grade and Ki67 expression also correlated with oestrogen receptor (ER) status. At 5 years post-operatively, 6/80 patients had died and 3 patients were alive but had cancer recurrence. High Ki67 expression significantly correlated with poor survival (disease-free and overall).
CONCLUSIONS
In this study, VEGFR3 and Ki67 expression but not mammaglobin-A correlated with breast tumour pathology. Positive Ki67 expression was also associated with a poor 5-year survival outcome.
PubMed: 31263371
DOI: 10.1177/1178223419858957 -
International Journal of Molecular... Aug 2023The continuous evolution of cancer biology has led to the discovery of mammaglobin, a potential novel biomarker for breast carcinoma. This review aims to unravel the... (Review)
Review
The continuous evolution of cancer biology has led to the discovery of mammaglobin, a potential novel biomarker for breast carcinoma. This review aims to unravel the enigmatic aspects of mammaglobin and elucidate its potential role in redefining the paradigm of breast carcinoma biomarkers. We will thoroughly examine its expression in tumoral and peritumoral tissues and its circulating levels in the blood, thereby providing insights into its possible function in cancer progression and metastasis. Furthermore, the potential application of mammaglobin as a non-invasive diagnostic tool and a target for personalized treatment strategies will be discussed. Given the increasing incidence of breast carcinoma worldwide, the exploration of novel biomarkers such as mammaglobin is crucial in advancing our diagnostic capabilities and treatment modalities, ultimately contributing to improved patient outcomes.
Topics: Humans; Female; Breast Neoplasms; Biomarkers; Biology
PubMed: 37686210
DOI: 10.3390/ijms241713407 -
OncoTargets and Therapy 2018Mammaglobin A expression in peripheral blood (PB) of breast carcinoma patients has been evaluated by various studies, but the findings have been inconsistent. This... (Review)
Review
Mammaglobin A expression in peripheral blood (PB) of breast carcinoma patients has been evaluated by various studies, but the findings have been inconsistent. This meta-analysis aimed to clarify the prognostic value of mammaglobin A in the PB of breast carcinoma patients and define its relationships with clinicopathological features. PubMed, EMBASE, and the Cochrane Library databases were systematically searched for eligible studies through September 26, 2017. A total of 20 studies involving 2,323 patients were analyzed, and the data were independently extracted by two researchers. The combined hazard ratios (HRs) with 95% CI was used to assess the association between survival data and plasma mammaglobin A expression, and odds ratios (ORs) and 95% CIs were used to assess the associations between clinicopathological parameters and plasma mammaglobin A expression. The results indicated that plasma mammaglobin A expression was a predictor of poor prognosis for breast carcinoma patients, with an HR of 2.08 (95% CI=1.48-2.91; <0.0001) for overall survival. Moreover, plasma mammaglobin A was significantly associated with lymph node metastasis (OR=2.00; 95% CI=1.17-3.45; =0.01) and advanced tumor stage (OR=3.01; 95% CI=1.57-5.77; =0.0009) in breast carcinoma patients. However, the results revealed that plasma mammaglobin A was not significantly associated with tumor size (OR=1.29; 95% CI=0.46-3.66; =0.63), tumor differentiation (OR=0.99; 95% CI=0.63-1.57; =0.97), menopausal status (OR=0.75; 95% CI=0.48-1.18; =0.22), estrogen receptor status (OR=0.78; 95% CI=0.44-1.36; =0.38), progesterone receptor status (OR=0.76; 95% CI=0.57-1.02; =0.07), or human epidermal growth factor receptor 2 status (OR=1.12; 95% CI=0.78-1.59; =0.54). In conclusion, the results demonstrate that positive plasma mammaglobin A expression might serve as a biomarker of poor prognosis for breast carcinoma patients.
PubMed: 29881297
DOI: 10.2147/OTT.S156556 -
Diagnostics (Basel, Switzerland) Mar 2023Human mammaglobin-A (SCGB2A2) is a secretory protein with an unknown function that is used as a diagnostic marker for breast cancer. However, other tumors can also...
Human mammaglobin-A (SCGB2A2) is a secretory protein with an unknown function that is used as a diagnostic marker for breast cancer. However, other tumors can also express mammaglobin-A. To comprehensively study patterns of mammaglobin-A expression, a tissue microarray containing 16,328 samples from 128 different tumor types as well as 608 samples of 76 different normal tissue types was analyzed using immunohistochemistry. Mammaglobin-A positivity was found in only a few normal tissues, including luminal cells of the breast as well as endocervical and endometrial glands. In tumor tissues, 37 of 128 tumor categories showed mamma-globin-A staining, 32 of which were derived from one of four organs: breast (6 tumor categories), endometrium (5 tumor categories), ovary (5 tumor categories), and salivary glands (16 tumor categories). Only five additional tumor types showed occasional weak mammaglobin positivity, including medullary thyroid cancer, teratoma of the testis, squamous cell carcinoma of the skin and pharynx, and prostatic adenocarcinoma. Among 1139 evaluable invasive breast carcinomas of no special type, low mammaglobin-A immunostaining was linked to high BRE grade ( = 0.0011), loss of estrogen and progesterone receptor expression ( < 0.0001 each), and triple-negative status ( < 0.0001) but not to patient survival. In endometrial cancer, mammaglobin-A loss was linked to an advanced tumor stage ( = 0.0198). Our data characterize mammaglobin-A as a highly specific marker for tumors derived from either the breast, female genitals, or salivary gland.
PubMed: 36980510
DOI: 10.3390/diagnostics13061202 -
Applied Immunohistochemistry &... Apr 2016Traditional markers mammaglobin and GCDFP15 show good specificity but lack sensitivity and can be difficult to interpret in small tissue samples. We undertook a... (Review)
Review
The Novel Marker GATA3 is Significantly More Sensitive Than Traditional Markers Mammaglobin and GCDFP15 for Identifying Breast Cancer in Surgical and Cytology Specimens of Metastatic and Matched Primary Tumors.
Traditional markers mammaglobin and GCDFP15 show good specificity but lack sensitivity and can be difficult to interpret in small tissue samples. We undertook a comparative study of the novel nuclear marker GATA3 (expression typically restricted to breast and urothelial carcinomas) and GCDFP15 and mammaglobin. We first compared quantitative mRNA expression levels of these 3 markers across a diverse set of over 6000 tumors and 500 normal samples from The Cancer Genome Atlas which showed dramatically higher GATA3 expression (>10-fold higher) in breast cancer as compared with GCDFP15 or mammaglobin (both P<2.2e-16), suggesting that GATA3 may represent a more sensitive marker of breast cancer than GCDFP15 or mammaglobin. We next examined protein expression by immunohistochemistry in 166 cases (including surgical and cytology specimens) of metastatic breast carcinoma and 54 cases with available matched primaries. One whole-slide section from each case was stained for monoclonal GATA3 (L50-823), monoclonal mammaglobin (31A5), and monoclonal GCDFP15 (EP1582Y). Staining intensity (0 to 3+) and extent (0% to 100%) were scored with an H-score calculated (range, 0 to 300). Sensitivities by varying H-score cutoffs for a positive result in metastatic breast carcinoma among GATA3/GCDFP15/mammaglobin, respectively, were as follows: any H-score=95%/65%/78%, H-score>50=93%/37%/47%, H-score>100=90%/25%/27%, H-score>150=86%/21%/19%, H-score>200=73%/18%/9%, H-score>250=66%/14%/6%. Significant staining differences by specimen type, tumor subtype/grade, or ER/PR/HER2 status were not identified. Significantly stronger correlation was observed between primary/metastatic GATA3 expression [Pearson's correlation=0.81 (0.68-0.89)] as compared with the primary/metastatic correlations of GCDFP15 [Pearson's correlation=0.57 (0.33-0.74)] and mammaglobin [Pearson's correlation=0.50 (0.24-0.70)] (both P<0.05). In conclusion, the novel marker GATA3 stains a significantly higher proportion of both primary and metastatic breast carcinomas than GCDFP15 or mammaglobin with stronger and more diffuse staining, helpful in cases with small tissue samples. The matched primary/metastatic expression of GATA3 is also more consistent. We propose that GATA3 be included among a panel of confirmatory markers for metastatic breast carcinoma.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Breast Neoplasms; Carrier Proteins; Female; GATA3 Transcription Factor; Glycoproteins; Humans; Mammaglobin A; Mammaglobin B; Membrane Transport Proteins; Middle Aged; Neoplasm Metastasis; Sensitivity and Specificity
PubMed: 25906123
DOI: 10.1097/PAI.0000000000000186 -
Scientific Reports Nov 2017Mammaglobin B (MGB2) and mammaglobin A (MGB1) are proteins expressed in metastatic breast cancers. The early detection of circulating tumor cells (CTCs) in breast cancer...
Mammaglobin B (MGB2) and mammaglobin A (MGB1) are proteins expressed in metastatic breast cancers. The early detection of circulating tumor cells (CTCs) in breast cancer patients is crucial to decrease mortality rate. Herein, novel aptamers were successfully selected and characterized against MGB2 and MGB1 proteins using a hybrid SELEX approach. The potential use of the selected aptamers in breast CTC detection was studied using spiked breast cancer cells in whole blood lysate. The results obtained from this study showed that the selected aptamers (MAMB1 and MAMA2) bind to their target breast cancer cell lines with high affinity (low nanomolar K values) and specificity. They also bind to their free recombinant target proteins and show minimal non-specific binding to normal and other cancer cell lines. Additionally, they were able to distinguish a low number of breast cancer cells spiked in whole blood lysate containing normal blood cells. The results obtained in this study indicate the great potential for the use of aptamers to detect MGB1 and MGB2 protein biomarkers, expressed on the surface of breast CTCs.
Topics: Aptamers, Nucleotide; Biomarkers, Tumor; Breast Neoplasms; Cell Line; Computational Biology; Flow Cytometry; Hematologic Tests; Humans; Mammaglobin A; Mammaglobin B; Microscopy, Fluorescence; Neoplastic Cells, Circulating; SELEX Aptamer Technique; Sensitivity and Specificity
PubMed: 29101327
DOI: 10.1038/s41598-017-13751-z -
European Journal of Histochemistry : EJH Apr 2022Increasing evidence has shown that mammaglobin, GATA-binding protein 3 (GATA3), and epithelial growth factor receptor (EGFR) have unique clinical implications for breast...
Increasing evidence has shown that mammaglobin, GATA-binding protein 3 (GATA3), and epithelial growth factor receptor (EGFR) have unique clinical implications for breast cancer subtyping and classification, as well as for breast cancer targeted therapy. It is particularly important to clarify the correlation between their expression and different molecular breast carcinoma subtypes to better understand the molecular basis of the subtypes and to identify effective therapeutic targets for the disease. This study aimed to evaluate mammaglobin, GATA3, and EGFR expression in different breast cancer subtypes, as well as their clinical significance. Subjects of the study included 228 patients with breast cancer at The First Affiliated Hospital of University of Science and Technology of China. They were divided into triple negative (TN), Luminal A, Luminal B, and HER-2 positive (HER-2.P) breast cancer groups based on molecular classification. Immunohistochemical methods were used to detect mammaglobin, GATA3, and EGFR expression in cases of different molecular subtypes before determining the correlation between protein expression and subtype. Mammaglobin and GATA3 expression levels were found to significantly vary with respect to histopathological grade, lymph node status, and molecular subtype; EGFR expression was significantly correlated with breast cancer histopathological grade and molecular subtype. For breast cancer, the expression levels of mammaglobin and GATA3, as well as mammaglobin and EGFR, were significantly correlated. In addition, there was a significantly negative correlation between the expression levels of GATA3 and EGFR in breast cancer tissue samples, especially in HER-2.P samples. These findings provide a theoretical basis for assessing breast cancer clinical prognosis based on the cancer subtype, and hence, have significant practical value.
Topics: Biomarkers, Tumor; Breast Neoplasms; Carrier Proteins; ErbB Receptors; Female; GATA3 Transcription Factor; Humans; Immunohistochemistry; Mammaglobin A
PubMed: 35388661
DOI: 10.4081/ejh.2022.3315 -
Applied Immunohistochemistry &... Jul 2014Metastases represent the most common type of intracranial neoplasm. In women, 30% of such tumors derive from breast carcinoma. In neurosurgical cases with ambiguous... (Clinical Trial)
Clinical Trial
Metastases represent the most common type of intracranial neoplasm. In women, 30% of such tumors derive from breast carcinoma. In neurosurgical cases with ambiguous cellular morphology and/or limited biopsy material, immunohistochemistry (IHC) is often performed to distinguish metastases from primary central nervous system (CNS) neoplasms. IHC for mammaglobin-A (MGA), a protein expressed in a majority of breast carcinomas, is commonly applied in this setting, but its utility for distinguishing primary CNS neoplasms from metastatic breast carcinoma is unknown; the reactivity of MGA in primary and metastatic CNS neoplasms has never been described. Here, we describe the frequency and patterns of IHC reactivity for MGA in metastatic and primary CNS neoplasms from patients with well-documented histories of breast carcinoma. Following a published protocol previously applied to non-CNS neoplasms, MGA staining of moderate to strong intensity within 5% or more of a neoplasm was considered positive. On the basis of these criteria, 3 of 12 (25.0%) glioblastomas, 1 of 10 (10.0%) meningiomas, and 47 of 95 (49.5%) metastases were positive. Importantly, the cytoarchitectural staining characteristics among all 4 MGA-positive primary CNS neoplasms (cytoplasmic and nuclear) differed from those of the metastases (cytoplasmic and membranous). These findings suggest that MGA IHC staining intensity and distribution can distinguish metastases from primary CNS neoplasms (P=0.0086) in women with a history of breast carcinoma but also indicate that cytologic staining patterns must be interpreted for more accurate tumor classification.
Topics: Biomarkers, Tumor; Brain Neoplasms; Breast Neoplasms; Female; Glioblastoma; Humans; Mammaglobin A; Meningeal Neoplasms; Meningioma; Neoplasm Metastasis; Neoplasm Proteins; Retrospective Studies
PubMed: 23958549
DOI: 10.1097/PAI.0b013e318294ca46 -
Oncoimmunology Feb 2016We recently completed a phase 1 clinical trial demonstrating the safety of a mammaglobin-A DNA vaccine in patients with metastatic breast cancer. We are currently...
We recently completed a phase 1 clinical trial demonstrating the safety of a mammaglobin-A DNA vaccine in patients with metastatic breast cancer. We are currently enrolling patients with early stage breast cancer in a phase 1b clinical trial. The mammaglobin-A DNA vaccine will be administered concurrently with neoadjuvant endocrine therapy, providing a unique opportunity to examine the impact of vaccination in the tumor microenvironment.
PubMed: 27057470
DOI: 10.1080/2162402X.2015.1069940 -
Breast Cancer Research and Treatment Oct 2014Mammaglobin-A (MAM-A) is a secretory protein that is overexpressed in 80 % of human breast cancers. Its near-universal expression in breast cancer as well as its...
Mammaglobin-A (MAM-A) is a secretory protein that is overexpressed in 80 % of human breast cancers. Its near-universal expression in breast cancer as well as its exquisite tissue specificity makes it an attractive target for a breast cancer prevention vaccine, and we recently initiated a phase 1 clinical trial of a MAM-A DNA vaccine. Previously, we have identified multiple MAM-A CD8 T cell epitopes using a reverse immunology candidate epitope approach based on predicted binding, but to date no attempt has been made to identify epitopes using an unbiased approach. In this study, we used human T cells primed in vitro with autologous dendritic cells expressing MAM-A to systematically identify MAM-A CD8 T cell epitopes. Using this unbiased approach, we identified three novel HLA-A2-restricted MAM-A epitopes. CD8 T cells specific for these epitopes are able to recognize and lyse human breast cancer cells in a MAM-A-specific, HLA-A2-dependent fashion. HLA-A2(+)/MAM-A(+) breast cancer patients have an increased prevalence of CD8 T cells specific for these novel MAM-A epitopes, and vaccination with a MAM-A DNA vaccine significantly increases the number of these CD8 T cells. The identification and translational validation of novel MAM-A epitopes has important implications for the ongoing clinical development of vaccine strategies targeting MAM-A. The novel MAM-A epitopes represent attractive targets for epitope-based vaccination strategies, and can also be used to monitor immune responses. Taken together these studies provide additional support for MAM-A as an important therapeutic target for the prevention and treatment of breast cancer.
Topics: Amino Acid Sequence; Breast Neoplasms; CD8-Positive T-Lymphocytes; Cancer Vaccines; Epitopes, T-Lymphocyte; Female; HLA-A2 Antigen; Humans; Mammaglobin A; Molecular Sequence Data; Reproducibility of Results; Vaccines, DNA
PubMed: 25212176
DOI: 10.1007/s10549-014-3129-x