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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 -
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 -
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 -
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 -
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 -
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 -
Human Vaccines & Immunotherapeutics 2014DNA vaccination has emerged as an attractive immunotherapeutic approach against cancer due to its simplicity, stability, and safety. Results from numerous clinical... (Review)
Review
DNA vaccination has emerged as an attractive immunotherapeutic approach against cancer due to its simplicity, stability, and safety. Results from numerous clinical trials have demonstrated that DNA vaccines are well tolerated by patients and do not trigger major adverse effects. DNA vaccines are also very cost effective and can be administered repeatedly for long-term protection. Despite all the practical advantages, DNA vaccines face challenges in inducing potent antigen specific cellular immune responses as a result of immune tolerance against endogenous self-antigens in tumors. Strategies to enhance immunogenicity of DNA vaccines against self-antigens have been investigated including encoding of xenogeneic versions of antigens, fusion of antigens to molecules that activate T cells or trigger associative recognition, priming with DNA vectors followed by boosting with viral vector, and utilization of immunomodulatory molecules. This review will focus on discussing strategies that circumvent immune tolerance and provide updates on findings from recent clinical trials.
Topics: Animals; Antigens, Neoplasm; Cancer Vaccines; Dendritic Cells; Humans; Immunotherapy; Mice; Neoplasms; Tumor Escape; Vaccination; Vaccines, DNA
PubMed: 25625927
DOI: 10.4161/21645515.2014.980686 -
Signal Transduction and Targeted Therapy May 2020Although targeted therapy has been extensively investigated for breast cancers, a molecular target with broad application is currently unavailable due to the high...
Although targeted therapy has been extensively investigated for breast cancers, a molecular target with broad application is currently unavailable due to the high heterogeneity of these cancers. Mammaglobin-A (Mam-A), which is overexpressed in most breast carcinomas, has been proposed as a promising target. However, the lack of specific targeting moieties due to uncertain binding epitopes hampers further translational study. Here, seven potential epitopes of Mam-A were disclosed, and a unique epitope was then identified in most types of breast cancers, despite the genotypic heterogeneity. With phage display technology, the epitope was determined to be N-terminal amino acids 42-51 of Mam-A (N). Then, the N epitope-specific monoclonal antibody, mAb785, was conjugated to poly lactic-co-glycolic acid (PLGA) nanoparticles loaded with therapeutic agents, thereby enhancing the drug uptake and therapeutic efficacy in different genotypes of breast cancers. The computer simulation of the N epitope and the mAb785 structures, as well as their interactions, further revealed the specific targeting mechanism of the mAb785-conjugated nanoparticles to breast cancers.
Topics: Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Breast Neoplasms; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Epitopes; Female; Humans; Mammaglobin A; Nanoparticles; Neoplasm Proteins; T-Lymphocytes, Cytotoxic
PubMed: 32467564
DOI: 10.1038/s41392-020-0183-1