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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 -
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 -
BMC Veterinary Research Jun 2018Mammaglobin, a member of secretoglobin family has been recognized as a breast cancer associated protein. Though the exact function of the protein is not fully known, its...
BACKGROUND
Mammaglobin, a member of secretoglobin family has been recognized as a breast cancer associated protein. Though the exact function of the protein is not fully known, its expression has been reported to be upregulated in human breast cancer.We focused on studying the expression of mammaglobin-B gene and protein in canine mammary tumor (CMT) tissue. Expression of mammaglobin-B mRNA and protein were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC), respectively.
RESULTS
High levels of mammaglobin-B mRNA expression (6.663 ± 0.841times) was observed in CMT as compared to age and breed matched healthy controls. Further, expression of mammaglobin-B protein was detected in paraffin-embedded mammary tumor tissues from the same subjects by IHC. Mammaglobin-B protein was overexpressed only in 6.67% of healthy mammary glands while, a high level of its expression was scored in 76.7% of the CMT subjects. Moreover, no significant differences in terms of IHC score and qRT-PCR score with respect to CMT histotypes or tumor grades were observed, indicating that mammaglobin-B over-expression occurred irrespective of CMT types or grades.
CONCLUSION
Overall, significantly increased expression of mammaglobin-B protein was found in CMTs with respect to healthy mammary glands, which positively correlates to its transcript. These findings suggest that overexpression of mammaglobin-B is associated with tumors of canine mammary glands.
Topics: Animals; Dog Diseases; Dogs; Female; Gene Expression; Immunohistochemistry; Mammaglobin B; Mammary Neoplasms, Animal; Neoplasm Grading; RNA, Messenger; RNA, Neoplasm; Real-Time Polymerase Chain Reaction
PubMed: 29903015
DOI: 10.1186/s12917-018-1507-z -
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 -
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 -
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 -
Turk Patoloji Dergisi 2018Cytomorphologic differentiation of metastatic breast carcinoma from non breast metastases in cytological materials can be difficult. Current breast immunocytochemical... (Comparative Study)
Comparative Study
Can GATA3 Immunocytochemistry be Utilized as a Reliable Diagnostic Marker for Metastatic Breast Carcinoma in Cytological Materials? A Comparative Study with Mammaglobin and GCDFP-15 Expression.
OBJECTIVE
Cytomorphologic differentiation of metastatic breast carcinoma from non breast metastases in cytological materials can be difficult. Current breast immunocytochemical markers have low sensitivities. Transcription factor GATA 3 is a promising marker for detecting breast differentiation in cytological materials. The aim of the study was to assess the diagnostic value of GATA 3 as a breast differentiation marker in metastatic cytological materials and to compare it with expression of mammaglobin and gross cystic disease fluid protein-15 (GCDFP-15).
MATERIAL AND METHOD
We retrospectively retrieved 133 cases of metastatic breast carcinoma from the archive the of Cytology Unit between December 2013 and June 2015. They included 77 fine needle aspiration and 56 serous effusion samples. Forty-five cytological materials from non mammary metastatic tumors were used as a control. Immunostaining was performed on cell blocks for the presence of GATA 3, mammaglobin and GCDFP-15.
RESULTS
GATA 3 nuclear staining was detected in 82.7% of metastatic breast carcinomas, and 11.1% of metastatic non mammary adenocarcinomas (p < 0.001). GATA 3 sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 82.7%, 88.9%, 95.7%, 63.5% and 84.3%, respectively. Mammaglobin and GCDFP-15 staining of metastatic breast carcinoma cases was positive in 70.7% and 47.1%, respectively. GATA 3 staining was significantly higher compared with mammaglobin and GCDFP-15 (p < 0.001).
CONCLUSION
GATA 3 is more sensitive marker than mammaglobin and GCDFP-15 for diagnosing metastatic breast carcinoma in cytological cell block materials. Adding mammaglobin to GATA 3 resulted in improvement in its sensitivity. GATA 3 was occasionally positive in some metastatic non mammary carcinoma that may cause misdiagnosis.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Breast Neoplasms; Carrier Proteins; Female; GATA3 Transcription Factor; Glycoproteins; Humans; Mammaglobin A; Membrane Transport Proteins; Middle Aged; Retrospective Studies; Sensitivity and Specificity
PubMed: 29235613
DOI: 10.5146/tjpath.2017.01419 -
Journal of Cancer Research and Clinical... Feb 2018Male breast cancer is an uncommon disease often discovered in advanced stage; thus, in the setting of metastatic adenocarcinoma, breast origin must be taken to account....
BACKGROUND
Male breast cancer is an uncommon disease often discovered in advanced stage; thus, in the setting of metastatic adenocarcinoma, breast origin must be taken to account. Breast markers as NY-BR-1, GATA-3, mammaglobin, and BRST-2 are established tools for labelling primary and metastatic female breast cancer; however, none of them has been sufficiently studied in male breast cancer. The aim of this study was to analyze the expression of these markers in male breast cancer.
MATERIALS AND METHODS
Thirty consecutive cases of male breast cancer and eight loco-regional metastases were re-revaluated, assembled in tissue micro array (TMA), and stained with immunohistochemistry (IHC) for NY-BR-1, GATA-3, mammaglobin, and BRST-2. The IHC stains were scored either positive or negative. In addition, concordant expression patterns of primary tumors and matched metastasis were noted.
RESULTS
30 of 30 (100%) primary tumors and 8 of 8 (100%) metastases were positive for NY-BR-1. 30 of 30 (100%) primary tumors and 6 of 8 (75%) metastases were positive for GATA-3. 22 of 30 (73.3%) primary tumors and 6 of 8 (75%) metastases were positive for Mammaglobin. 18 of 30 (60%) primary tumors and 5 of 8 (62.5%) metastases were positive for BRST-2. Differences in staining percentage were not significant with Fisher's exact test.
CONCLUSION
We found a high sensitivity for all the markers analyzed. Moreover, the expression of NY-BR-1 and GATA-3 seemed the most effective for labelling male breast cancer in primary and metastatic setting.
Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Breast Neoplasms, Male; Carrier Proteins; Cohort Studies; GATA3 Transcription Factor; Glycoproteins; Humans; Immunohistochemistry; Male; Mammaglobin A; Membrane Transport Proteins; Middle Aged; Neoplasm Metastasis; Tissue Array Analysis
PubMed: 29116378
DOI: 10.1007/s00432-017-2542-z -
Clinical Cancer Research : An Official... Dec 2014Mammaglobin-A (MAM-A) is overexpressed in 40% to 80% of primary breast cancers. We initiated a phase I clinical trial of a MAM-A DNA vaccine to evaluate its safety and...
PURPOSE
Mammaglobin-A (MAM-A) is overexpressed in 40% to 80% of primary breast cancers. We initiated a phase I clinical trial of a MAM-A DNA vaccine to evaluate its safety and biologic efficacy.
EXPERIMENTAL DESIGN
Patients with breast cancer with stable metastatic disease were eligible for enrollment. Safety was monitored with clinical and laboratory assessments. The CD8 T-cell response was measured by ELISPOT, flow cytometry, and cytotoxicity assays. Progression-free survival (PFS) was described using the Kaplan-Meier product limit estimator.
RESULTS
Fourteen subjects have been treated with the MAM-A DNA vaccine and no significant adverse events have been observed. Eight of 14 subjects were HLA-A2(+), and the CD8 T-cell response to vaccination was studied in detail. Flow cytometry demonstrated a significant increase in the frequency of MAM-A-specific CD8 T cells after vaccination (0.9% ± 0.5% vs. 3.8% ± 1.2%; P < 0.001), and ELISPOT analysis demonstrated an increase in the number of MAM-A-specific IFNγ-secreting T cells (41 ± 32 vs. 215 ± 67 spm; P < 0.001). Although this study was not powered to evaluate progression-free survival (PFS), preliminary evidence suggests that subjects treated with the MAM-A DNA vaccine had improved PFS compared with subjects who met all eligibility criteria, were enrolled in the trial, but were not vaccinated because of HLA phenotype.
CONCLUSION
The MAM-A DNA vaccine is safe, capable of eliciting MAM-A-specific CD8 T-cell responses, and preliminary evidence suggests improved PFS. Additional studies are required to define the potential of the MAM-A DNA vaccine for breast cancer prevention and/or therapy.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Breast Neoplasms; CD8-Positive T-Lymphocytes; Cancer Vaccines; Combined Modality Therapy; Cytotoxicity, Immunologic; Epitopes, T-Lymphocyte; Female; Genetic Vectors; Humans; Interferon-gamma; Male; Mammaglobin A; Middle Aged; NK Cell Lectin-Like Receptor Subfamily K; Neoplasm Metastasis; Treatment Outcome; Tumor Necrosis Factor-alpha; Vaccination; Vaccines, DNA
PubMed: 25451106
DOI: 10.1158/1078-0432.CCR-14-0059 -
3 Biotech Jul 2019In the present study, the simultaneous application of gene of and - antigen on the induction of immune responses against breast cancer tumors was investigated in...
In the present study, the simultaneous application of gene of and - antigen on the induction of immune responses against breast cancer tumors was investigated in BALB/c mice. The pBudCE4.1-azurin-MAM-A recombinant vector was generated and prepared at a large scale. This recombinant vector alone or combined with chitosan nanoparticles was infused into the hip muscle of animals. Animals were divided into the "prevention" and "therapy" categories. The animals of prevention category were first, immunized by a recombinant vector and then exposed to chemical cancer inducers; while the animals in the therapy category were first treated with chemical compounds and then infused by a recombinant plasmid. The tumor tissues, infusion sites, and blood specimens were collected and examined by serological, molecular, and histological tests. The breast tumor incidence in the infused animals by recombinant plasmid alone or combined with nanoparticles (in both prevention and therapy categories) compared with infused mice by empty pBudCE4.1 vector was significantly decreased (< 0.05). These results were supported by histological studies using H&E staining. The ELISA and q-real-time PCR techniques showed the range of IFN-γ, IL-12, IL-4, and IL-17A cytokines in the infused mice by recombinant vector alone or combined with nanoparticles compared to the healthy mice and infused animals by intact pBudCE4.1 were significantly increased (< 0.05). Accordingly, the expression of the tumor markers , , and were significantly decreased in treated mice either by the sole recombinant vector or combined with nanoparticles (< 0.05). These findings indicated that pBudCE4.1-azurin-MAM-A recombinant vector plays an essential role against the formation and expansion of breast tumors in the animal model. In addition, this recombinant vector is safe and has the proper ability to stimulate the immune system. In addition, the chitosan nanoparticle represents a promising adjuvant for DNA vaccine delivery, which improves the immune system stimulation and boosts the vaccine performance.
PubMed: 31245235
DOI: 10.1007/s13205-019-1804-7