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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 -
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 -
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 -
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 -
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 -
Cancer Research Feb 2011Pathologic axillary lymph node (ALN) status is an important prognostic factor for staging breast cancer. Currently, status is determined by histopathology following...
Pathologic axillary lymph node (ALN) status is an important prognostic factor for staging breast cancer. Currently, status is determined by histopathology following surgical excision of sentinel lymph node(s), which is an invasive, time consuming, and costly procedure with potential morbidity to the patient. Here, we describe an imaging platform for noninvasive assessment of ALN status, eliminating the need for surgical examination of patients to rule out nodal involvement. A targeted imaging probe (MamAb-680) was developed by conjugation of a mammaglobin-A-specific monoclonal antibody to a near-infrared fluorescent dye. Using DNA and tissue microarray, mammaglobin-A was validated as a cell-surface target that is expressed in ALN-positive patient samples but is not expressed in normal lymph nodes. In vivo selectivity was determined by i.v. injection of MamAb-680 into mice with mammaglobin-A-positive and -negative mammary fat pad (MFP) tumors; and by peritumoral MFP injection of the targeted imaging probe in mice with spontaneous ALN metastases. Fluorescence imaging showed that probe was only retained in positive tumors and metastases. As few as 1,000 cells that endogenously express mammaglobin-A were detected in ALN, indicating high sensitivity of this method. Translation of this approach offers considerable potential as a noninvasive clinical strategy to stage breast cancer.
Topics: Animals; Antibodies, Monoclonal; Antibody Specificity; Breast Neoplasms; Diagnostic Imaging; Female; Fluorescent Dyes; Humans; Immunoconjugates; Lymph Nodes; Lymphatic Metastasis; Mammaglobin A; Mice; Mice, Nude; Neoplasm Proteins; RNA, Messenger; Transplantation, Heterologous; Uteroglobin
PubMed: 21169406
DOI: 10.1158/0008-5472.CAN-10-3091 -
PloS One 2013Mammaglobin A (MGBA) is a novel breast cancer-associated antigen almost exclusively over-expressed in primary and metastatic human breast cancers, making it a potential...
Mammaglobin A (MGBA) is a novel breast cancer-associated antigen almost exclusively over-expressed in primary and metastatic human breast cancers, making it a potential therapeutic target for breast cancer. The development of dendritic cell (DC)-induced tumor antigen specific CD8(+) cytotoxic T lymphocytes (CTLs) may hold promise in cancer immunotherapy. In this study we constructed recombinant replication-defective adenoviral (Ad) vectors encoding MGBA and evaluated their ability to trigger anti-tumor immunity in vitro. DCs were isolated from the human peripheral blood monocyte cells (PBMCs) of two HLA-A33(+) healthy female volunteers, and infected with adenovirus carrying MGBA cDNA (Ad-MGBA). After that, the Ad-MGBA-infected DCs were used to stimulate CD8(+) CTLs in vitro and the latter was used for co-culture with breast cancer cell lines. The data revealed that infection with Ad-MGBA improved DC maturation and up-regulated the expression of co-stimulatory molecules and the secretion of interleukin-12 (IL-12), but down-regulated interleukin-10 (IL-10) secretion from DCs. Ad-MGBA-infected DC-stimulated CD8(+)CTLs displayed the highest cytotoxicity towards HLA-A33(+)/MGBA(+) breast cancer MDA-MB-415 cells compared with other CD8(+)CTL populations, and compared with the cytotoxicity towards HLA-A33(-)/MGBA(+) breast cancer HBL-100 cells and HLA-A33(-)/MGBA(-) breast cancer MDA-MB 231 cells. In addition, Ad-MGBA-infected DC-stimulated CD8(+) CTLs showed a high level of IFNγ secretion when stimulated with HLA-A33(+)/MGBA(+) breast cancer MDA-MB-415 cells, but not when stimulated with HLA-A33(-)/MGBA(+) HBL-100 and HLA-A33(-)/MGBA(-)MDA-MB-231 cells. In addition, killing of CD8(+)CTLs against breast cancer was in a major histocompability complex (MHC)-limited pattern. Finally, the data also determined the importance of TNF-α in activating DCs and T cells. These data together suggest that MGBA recombinant adenovirus-infected DCs could induce specific anti-tumor immunity against MGBA(+) breast cancers, which could provide a novel strategy in the immunotherapy of breast cancer.
Topics: Adenoviridae; Adult; Breast Neoplasms; Cell Line, Tumor; Cells, Cultured; Coculture Techniques; Cytotoxicity, Immunologic; Dendritic Cells; Female; Genetic Vectors; Humans; Immunotherapy; Interferon-gamma; Interleukin-10; Interleukin-12; Mammaglobin A; T-Lymphocytes, Cytotoxic
PubMed: 23650543
DOI: 10.1371/journal.pone.0063055 -
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 -
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