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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 -
Virchows Archiv : An International... May 2023The lack of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 expression in breast cancer (BC) is the basis for the categorization...
The lack of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 expression in breast cancer (BC) is the basis for the categorization of the tumour as triple negative breast carcinoma (TNBC). The majority of TNBCs are aggressive tumours with common metastases and decreased expression of markers that could help in identifying the metastatic lesion as of mammary origin. Breast markers, such as gross cystic disease fluid protein-15 (GCDPF-15), GATA binding protein 3 (GATA3), mammaglobin (MGB) and SOX10, are not uniquely specific to BC. Our aim was to evaluate trichorhinophalangeal syndrome type 1 (TRPS1) protein as a breast marker in a series of cytokeratin-5-expressing TNBC, mostly corresponding to basal-like TNBCs, previously characterized for the expression of other breast markers. One hundred seventeen TNBCs in tissue microarrays were immunostained for TRPS1. The cut-off for positivity was ≥ 10%. The reproducibility of this classification was also assessed. TRPS1 positivity was detected in 92/117 (79%) cases, and this exceeded the expression of previously tested markers like SOX10 82 (70%), GATA3 11 (9%), MGB 10 (9%) and GCDFP-15 7 (6%). Of the 25 TRPS1-negative cases, 11 were positive with SOX10, whereas 5 to 6 dual negatives displayed positivity for the other makers. The evaluation showed substantial agreement. Of the five markers compared, TRPS1 seems the most sensitive marker for the mammary origin of CK5-expressing TNBCs. Cases that are negative are most often labelled with SOX10, and the remainder may still demonstrate positivity for any of the 3 other markers. TRPS1 has a place in breast marker panels.
Topics: Humans; Female; Triple Negative Breast Neoplasms; Biomarkers, Tumor; Breast Neoplasms; Keratin-5; Reproducibility of Results; Mammaglobin A; Carrier Proteins; GATA3 Transcription Factor; Repressor Proteins
PubMed: 37012444
DOI: 10.1007/s00428-023-03535-4 -
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 -
Asian Pacific Journal of Cancer... Feb 2023Mammaglobin and GCDFP-15 are traditional immunohistochemistry (IHC) markers utilized to recognize metastasis of breast carcinoma in an unknown primary. GATA-3 is...
BACKGROUND AND OBJECTIVE
Mammaglobin and GCDFP-15 are traditional immunohistochemistry (IHC) markers utilized to recognize metastasis of breast carcinoma in an unknown primary. GATA-3 is increasingly being used as a marker of primary breast origin. This study was done to evaluate and compare GATA-3 with GCDFP-15 and Mammaglobin in invasive primary including metastatic and triple negative breast carcinomas.
METHODS
Immunohistochemistry for GATA-3, GCDFP-15 and Mammaglobin was applied on 100 cases of primary breast carcinomas, including 20 triple negative cases and 30 cases of metastatic breast carcinomas. Staining scores were given for each marker by multiplying the percentage of positive tumor cells by the intensity of staining (1+, 2+ or 3+), with scores ranging from 0 to 300. Staining score of 1 or more was considered positive.
RESULTS
GATA-3 was expressed in 92% of primary, 80% of metastatic and 60% of triple negative breast carcinomas, with an average staining score of 270. Mammaglobin was expressed in 68% of primary, 56.6% of metastatic and 25% of triple negative breast carcinomas, with an average staining score of 180. GCDFP-15 was expressed in 48% of primary, 26.6% of metastatic and 05% of breast carcinomas, with an average staining score of 60. GATA-3 demonstrated to have higher staining score (average of 270) than other two markers in maximum number of cases.
CONCLUSION
GATA-3 has a higher sensitivity and increased staining scores in primary breast carcinomas, metastatic breast carcinomas as well as in triple negative breast carcinomas.
Topics: Humans; Asian People; Breast; Staining and Labeling; Triple Negative Breast Neoplasms; Mammaglobin A; Biomarkers, Tumor
PubMed: 36853299
DOI: 10.31557/APJCP.2023.24.2.509 -
Breast Cancer Research : BCR Oct 2022Metastatic breast carcinoma is commonly considered during differential diagnosis when metastatic disease is detected in females. In addition to the tumor morphology and...
BACKGROUND
Metastatic breast carcinoma is commonly considered during differential diagnosis when metastatic disease is detected in females. In addition to the tumor morphology and documented clinical history, sensitive and specific immunohistochemical (IHC) markers such as GCDFP-15, mammaglobin, and GATA3 are helpful for determining breast origin. However, these markers are reported to show lower sensitivity in certain subtypes, such as triple-negative breast cancer (TNBC).
MATERIALS AND METHODS
Using bioinformatics analyses, we identified a potential diagnostic panel to determine breast origin: matrix Gla protein (MGP), transcriptional repressor GATA binding 1 (TRPS1), and GATA-binding protein 3 (GATA3). We compared MGP, TRPS1, and GATA3 expression in different subtypes of breast carcinoma of (n = 1201) using IHC. As a newly identified marker, MGP expression was also evaluated in solid tumors (n = 2384) and normal tissues (n = 1351) from different organs.
RESULTS
MGP and TRPS1 had comparable positive expression in HER2-positive (91.2% vs. 92.0%, p = 0.79) and TNBC subtypes (87.3% vs. 91.2%, p = 0.18). GATA3 expression was lower than MGP (p < 0.001) or TRPS1 (p < 0.001), especially in HER2-positive (77.0%, p < 0.001) and TNBC (43.3%, p < 0.001) subtypes. TRPS1 had the highest positivity rate (97.9%) in metaplastic TNBCs, followed by MGP (88.6%), while only 47.1% of metaplastic TNBCs were positive for GATA3. When using MGP, GATA3, and TRPS1 as a novel IHC panel, 93.0% of breast carcinomas were positive for at least two markers, and only 9 cases were negative for all three markers. MGP was detected in 36 cases (3.0%) that were negative for both GATA3 and TRPS1. MGP showed mild-to-moderate positive expression in normal hepatocytes, renal tubules, as well as 31.1% (99/318) of hepatocellular carcinomas. Rare cases (0.6-5%) had focal MGP expression in renal, ovarian, lung, urothelial, and cholangiocarcinomas.
CONCLUSIONS
Our findings suggest that MGP is a newly identified sensitive IHC marker to support breast origin. MGP, TRPS1, and GATA3 could be applied as a reliable diagnostic panel to determine breast origin in clinical practice.
Topics: Female; Humans; Triple Negative Breast Neoplasms; Breast Neoplasms; Biomarkers, Tumor; GATA3 Transcription Factor; Mammaglobin A; Calcium-Binding Proteins; Repressor Proteins; Matrix Gla Protein
PubMed: 36284362
DOI: 10.1186/s13058-022-01569-1 -
FEBS Open Bio Oct 2022Overexpression of human epidermal growth factor receptor 2 (HER2) in various cancers is correlated with poor patient survival. Trastuzumab, a recombinant humanized...
Overexpression of human epidermal growth factor receptor 2 (HER2) in various cancers is correlated with poor patient survival. Trastuzumab, a recombinant humanized monoclonal antibody against HER2, has been considered to be a first-line therapy for HER2-positive breast cancer patients, but its usefulness is limited by the development of resistance. In this study, we established resistant cells by long-term treatment with trastuzumab. These cells showed higher proliferation, invasion, and migration abilities than the wild-type cells. Mammaglobin 1 (MGB1), cyclin D1, E1, A2, and phosphorylated NF-κB (p-p65) were upregulated in resistant cells. These proteins regulate cell proliferation, migration, and invasion of resistant cells. Depletion of MGB1 decreased cyclin and p-p65 expression. Cyclin D1 and A2, but not E1 expression, were affected by p-p65 downregulation. In summary, our results indicate that MGB1 expression is increased in breast cancer cells that have gained resistance to trastuzumab, and suggest that MGB1 promotes aggressiveness through cyclin and NF-κB regulation.
Topics: Breast Neoplasms; Cell Line, Tumor; Cyclin D1; Female; Humans; Mammaglobin A; NF-kappa B; Trastuzumab
PubMed: 35945910
DOI: 10.1002/2211-5463.13468 -
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 -
Journal For Immunotherapy of Cancer Oct 2020We previously showed selectively hampered activation of lymph node-resident (LNR) dendritic cell (DC) subsets in the breast cancer (BrC) sentinel lymph node (SLN) to...
BACKGROUND
We previously showed selectively hampered activation of lymph node-resident (LNR) dendritic cell (DC) subsets in the breast cancer (BrC) sentinel lymph node (SLN) to precede a state of profound T cell anergy. Reactivating these DC subsets by intratumoral delivery of the Toll-like receptor-9 (TLR9) agonist CpG-B could potentially offer a promising immune therapeutic strategy to combat this immune suppression and prevent disease spread. Unfortunately, CpG-B can limit its own immune stimulatory activity through direct TLR9-mediated activation of signal transducer and activator of transcription 3 (STAT3), pinpointed as a key regulator of immune suppression in the tumor microenvironment. Here, we have investigated whether in vitro exposure to CpG-B, with or without simultaneous inhibition of STAT3 signaling, could overcome immune suppression in BrC SLN.
METHODS
Immune modulatory effects of CpG-B (CPG7909) with or without the JAK2/STAT3 inhibitor (STAT3i) AG490 were assessed in ex vivo cultured BrC SLN-derived single-cell suspensions (N=29). Multiparameter flow cytometric analyses were conducted for DC and T cell subset characterization and assessment of (intracellular) cytokine profiles. T cell reactivity against the BrC-associated antigen Mammaglobin-A was determined by means of interferon-γ ELISPOT assay.
RESULTS
Although CpG-B alone induced activation of all DC subsets, combined inhibition of the JAK2/STAT3 pathway resulted in superior DC maturation (ie, increased CD83 expression), with most profound activation and maturation of LNR DC subsets. Furthermore, combined CpG-B and JAK2/STAT3 inhibition promoted Th1 skewing by counterbalancing the CpG-induced Th2/regulatory T cell response and significantly enhanced Mammaglobin-A specific T cell reactivity.
CONCLUSION
Ex vivo immune modulation of the SLN by CpG-B and simultaneous JAK2/STAT3 inhibition can effectively overcome BrC-induced immune suppression by preferential activation of LNR DC, ultimately restoring type 1-mediated antitumor immunity, thereby securing a BrC-specific T cell response. These findings provide a clear rationale for clinical exploration of SLN-immune potentiation through local CpG/STAT3i administration in patients with BrC.
Topics: Breast Neoplasms; Dendritic Cells; Female; Humans; Immunomodulation; STAT3 Transcription Factor; Sentinel Lymph Node; Tumor Microenvironment
PubMed: 33046620
DOI: 10.1136/jitc-2020-000761 -
Saudi Journal of Biological Sciences Sep 2020Azurin protein of is an anti-tumor agent against breast cancer and mammaglobin-A (MAM-A) protein is a specific antigen on the surface of MCF-7 for induction of cellular...
Azurin protein of is an anti-tumor agent against breast cancer and mammaglobin-A (MAM-A) protein is a specific antigen on the surface of MCF-7 for induction of cellular immune. The purpose of the present study was to investigate the effects of simultaneous expression of and human genes on the mRNA expression level of apoptosis-related and cell cycle genes in MCF-7 breast cancer cell line. The recombinant or empty plasmids were separately transferred into MCF-7 cells using Lipofectamine reagent. Flow cytometry was done to detect cell death and apoptosis. The expression of genes were evaluated by IF assay, RT-PCR and western blot methods. Finally, apoptosis-related and cell cycle genes expression was examined in transformed and non-transformed MCF-7 cells by qPCR method. The successful expression of and genes in the MCF-7 cell were confirmed by RT-PCR, IF and western blotting. The apoptosis assay was showed a statistically significant ( < 0.05) difference after transfection. The expression of , , and genes in transformed cells compare with non-transformed and transformed MCF-7 by pBudCE4.1 were increased statistically significant ( < 0.05) increases. Although, the increase of and expressions in transformed cells were not statistically significant ( > 0.05). Co-expression of and genes could induce apoptosis and necrosis in human MCF-7 breast cancer cells by up-regulation of , and genes. In future researches, it must be better the immune stimulation of pBudCE4.1-azurin-MAM-A recombinant vector in animal models and therapeutic approaches will be evaluated.
PubMed: 32884412
DOI: 10.1016/j.sjbs.2020.04.007 -
Scientific Reports Aug 2020Despite all the advances in the management of breast cancer (BC), patients with distance metastasis are still considered incurable with poor prognosis. For that reason,...
Despite all the advances in the management of breast cancer (BC), patients with distance metastasis are still considered incurable with poor prognosis. For that reason, early detection of the metastatic lesions is crucial to improve patients' life span as well as quality of life. Many markers were proposed to be used as biomarkers for metastatic BC lesions, however many of them lack organ specificity. This highlights the need for novel markers that are more specific in detecting disseminated BC lesions. Here, we investigated mammaglobin-1 expression as a potential and specific marker for metastatic BC lesions using our patient cohort consisting of 30 newly diagnosed BC patients. For all patients, bone marrow (BM) aspiration, BM biopsy stained by H&E and BM immunohistochemically stained for mammaglobin-1 were performed. In addition, the CA15-3 in both serum and bone marrow plasma was also evaluated for each patient. Indeed, mammaglobin-1 immuno-staining was able to detect BM micrometastases in 16/30 patients (53.3%) compared to only 5/30 patients (16.7%) in BM biopsy stained by H&E and no cases detected by BM aspirate (0%). In addition, our results showed a trend of association between mammaglobin-1 immunoreactivity and the serum and BM plasma CA15-3. Further validation was done using large publicly available databases. Our results showed that mammaglobin-1 gene expression to be specifically upregulated in BC patients' samples compared to normal tissue as well as samples from other cancers. Moreover, our findings also showed mammaglobin-1 expression to be a marker of tumour progression presented as lymph nodes involvement and distant metastasis. These results provide an initial evidence for the use of mammaglobin-1 (SCGB2A2) immunostaining in bone marrow as a tool to investigate early BM micrometastases in breast cancer.
Topics: Biomarkers, Tumor; Biopsy; Bone Marrow; Bone Marrow Neoplasms; Breast Neoplasms; Cohort Studies; Early Detection of Cancer; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Mammaglobin A; Mucin-1; Neoplasm Micrometastasis; RNA, Messenger; Suction
PubMed: 32747636
DOI: 10.1038/s41598-020-70012-2