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Genetics and Molecular Research : GMR 2010Detection of residual tumor cells in the circulation can provide prognostic as well as therapeutic information and help in identifying patients at high risk for...
Detection of residual tumor cells in the circulation can provide prognostic as well as therapeutic information and help in identifying patients at high risk for developing metastases. Maspin and mammaglobin are two molecules that are specifically associated with breast cancer. We looked for mammaglobin and maspin transcripts in the peripheral blood of patients with breast cancer and evaluated their utility as a marker of the response to therapy. Maspin and mammaglobin transcripts were analyzed in 85 breast-cancer patients by nested RT-PCR, prior to and after treatment. Before therapy, 10 patients were found positive for mammaglobin and 20 patients were positive for maspin. In four patients, both transcripts were detected. Immediately following treatment, only one patient was still positive for mammaglobin while maspin transcripts persisted in three patients. Disease progression was observed mainly in patients in whom maspin transcripts were not detectable. Molecular detection of circulating tumor cells during therapy based on analysis for mammaglobin and maspin transcripts is an easy and practical method that can be applied to follow-up patients. We suggest that detection of mammaglobin mRNA is useful to determine the effect of therapy while maspin transcripts may indicate more aggressive disease.
Topics: Adult; Biomarkers, Tumor; Breast Neoplasms; Disease Progression; Female; Humans; Mammaglobin A; Middle Aged; Neoplasm Proteins; Neoplastic Cells, Circulating; Prognosis; RNA, Messenger; RNA, Neoplasm; Serpins; Transcription, Genetic; Uteroglobin
PubMed: 20092039
DOI: 10.4238/vol9-1gmr649 -
Breast (Edinburgh, Scotland) Oct 2010There are limited data that compare the utility of immunohistochemical detection of mammaglobin with Gross Cystic Disease Fluid Protein-15 (GCDFP-15) in locally...
There are limited data that compare the utility of immunohistochemical detection of mammaglobin with Gross Cystic Disease Fluid Protein-15 (GCDFP-15) in locally recurrent and metastatic breast cancers. Forty-three local and 72 distant recurrences of breast cancer, 8 metastatic lesions to the breast from other organs, and 30 metastases from non-breast primaries were immunohistochemically stained with mammaglobin and GCDFP-15 antibodies. Mammaglobin was expressed in 55 (47.8%) and GCDFP-15 detected in 13 (11.3%) locally and distantly recurrent breast cancers. A higher percentage of tumor cells was stained with mammaglobin at greater staining intensity than GCDFP-15, for both metastatic and locally recurrent breast cancers. The difference in staining intensity as well as mean percentage of tumor cells stained for both markers was statistically significant (p < 0.005). Metastases to the breast from other organs and metastatic lesions from non-breast primaries were uniformly negative for both mammaglobin and GCDFP-15. Our study demonstrates that immunohistochemical analysis of mammaglobin is superior to GCDFP-15 in detecting a tumor of breast origin, and can be incorporated into immunohistochemical panels evaluating tumors from unknown primary sites.
Topics: Adenocarcinoma, Mucinous; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Carcinoma, Papillary; Carrier Proteins; Female; Glycoproteins; Humans; Immunohistochemistry; Mammaglobin A; Membrane Transport Proteins; Middle Aged; Neoplasm Metastasis; Neoplasm Proteins; Neoplasm Recurrence, Local; Neoplasms, Unknown Primary; Sensitivity and Specificity; Uteroglobin
PubMed: 20347310
DOI: 10.1016/j.breast.2010.02.007 -
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 -
The Indian Journal of Medical Research May 2014Human mammaglobin is a member of the uteroglobin proteins family that has recently been tested as a specific marker for breast cancer. While low levels may be seen in... (Review)
Review
Human mammaglobin is a member of the uteroglobin proteins family that has recently been tested as a specific marker for breast cancer. While low levels may be seen in normal breast tissue, expression is increased dramatically in breast cancer and is correlated with higher grade. Detection in blood and body fluids is also correlated with cancer metastasis, and its levels with prognosis. This promises to be a useful screen for early detection of breast cancer, especially in high risk individuals. Mammoglobin has also been used for immunotherapeutic targeting of breast cancer cells. However, there are some controversies regarding its diagnostic efficacy and prognostic value, which warrant further study.
Topics: Biomarkers, Tumor; Breast Neoplasms; Female; Humans; Lymphatic Metastasis; Mammaglobin A; Prognosis; RNA, Messenger; Uteroglobin
PubMed: 25027076
DOI: No ID Found -
Anticancer Research 2008Mammaglobin (SCGB2A2) and lipophilin B (SCGB1D2) are members of the secretoglobin polypeptide family. Mammaglobin has been shown to be overexpressed in breast tumor...
BACKGROUND
Mammaglobin (SCGB2A2) and lipophilin B (SCGB1D2) are members of the secretoglobin polypeptide family. Mammaglobin has been shown to be overexpressed in breast tumor tissue, indicating that mammaglobin might confer a growth advantage to mammaglobin-expressing tumor cells.
MATERIALS AND METHODS
The mammaglobin and lipophilin B mRNA expression levels were investigated in seven breast tumors and matched nonneoplastic tissues from the same patients using quantitative real-time RT-PCR. The effect of mammaglobin and lipophilin B expression on breast cancer cell proliferation rates was investigated by analyzing retrovirally transduced Hs578T cell clones. Cell proliferation rates were determined during the exponential growth phase by analyzing the change in lactate dehydrogenase activity over time.
RESULTS
All analyzed breast cancer tumors had lower expression levels of mammaglobin and lipophilin B than the respective mean level of the nonneoplastic breast tissues; no prominent overexpression was evident. There was high variability in the expression of mammaglobin and lipophilin B among the non-neoplastic samples, showing that caution should be taken when evaluating their over- and underexpression in tumors. The expression levels of mammaglobin and lipophilin B correlated with each other in the analyzed samples (p = 0.001). Ectopic overexpression of mammaglobin and lipophilin B did not affect the cell proliferation rate of Hs578T breast carcinoma cells in vitro.
CONCLUSION
Our findings suggest that the overexpression of mammaglobin observed in certain breast tumors is an epiphenomenon not causally involved in breast carcinogenesis.
Topics: Aged; Breast Neoplasms; Cell Growth Processes; Cell Lineage; Female; Humans; Mammaglobin A; Middle Aged; Myelin Proteins; Neoplasm Proteins; Proteolipids; RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction; Secretoglobins; Transduction, Genetic; Uteroglobin
PubMed: 18630503
DOI: No ID Found -
PloS One 2012Adoptive T cell therapy has proven to be beneficial in a number of tumor systems by targeting the relevant tumor antigen. The tumor antigen targeted in our model is...
Adoptive T cell therapy has proven to be beneficial in a number of tumor systems by targeting the relevant tumor antigen. The tumor antigen targeted in our model is Mammaglobin-A, expressed by approximately 80% of human breast tumors. Here we evaluated the use of adoptively transferred Mammaglobin-A specific CD8 T cells in combination with low dose irradiation to induce breast tumor rejection and prevent relapse. We show Mammaglobin-A specific CD8 T cells generated by DNA vaccination with all epitopes (Mammaglobin-A2.1, A2.2, A2.4 and A2.6) and full-length DNA in vivo resulted in heterogeneous T cell populations consisting of both effector and central memory CD8 T cell subsets. Adoptive transfer of spleen cells from all Mammaglobin-A2 immunized mice into tumor-bearing SCID/beige mice induced tumor regression but this anti-tumor response was not sustained long-term. Additionally, we demonstrate that only the adoptive transfer of Mammaglobin-A2 specific CD8 T cells in combination with a single low dose of irradiation prevents tumors from recurring. More importantly we show that this single dose of irradiation results in the down regulation of the macrophage scavenger receptor 1 on dendritic cells within the tumor and reduces lipid uptake by tumor resident dendritic cells potentially enabling the dendritic cells to present tumor antigen more efficiently and aid in tumor clearance. These data reveal the potential for adoptive transfer combined with a single low dose of total body irradiation as a suitable therapy for the treatment of established breast tumors and the prevention of tumor recurrence.
Topics: Adoptive Transfer; Animals; Breast Neoplasms; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Cytotoxicity, Immunologic; Dendritic Cells; Epitopes, T-Lymphocyte; Female; Humans; Immunologic Memory; Interferon-gamma; Interleukin-7 Receptor alpha Subunit; L-Selectin; Lipid Metabolism; Mammaglobin A; Mice; Mice, SCID; Mice, Transgenic; Scavenger Receptors, Class A; Tumor Necrosis Factor Receptor Superfamily, Member 7; Tumor Necrosis Factor-alpha; Vaccines, DNA; Whole-Body Irradiation
PubMed: 22911764
DOI: 10.1371/journal.pone.0041240 -
International Journal of Cancer Dec 2002Mammaglobin-A is highly overexpressed in breast cancer cell lines and primary breast tumors. This pattern of expression is restricted to mammary epithelium and...
Mammaglobin-A is highly overexpressed in breast cancer cell lines and primary breast tumors. This pattern of expression is restricted to mammary epithelium and metastatic breast tumors. Thus, mammaglobin-A-specific T cell immune responses may provide an important approach for the design of breast cancer-specific immunotherapy. The purpose of our study was to define the T cell-mediated immune response to mammaglobin-A. We determined that the frequency of mammaglobin-A-reactive CD8+ and CD4+ T cells in breast cancer patients is significantly higher than that observed in healthy female controls using limiting dilution analyses (p = 0.026 and p = 0.02, respectively). We identified 8 mammaglobin-A-derived 9-mer peptides with the highest binding affinity for the HLA-A3 molecule (Mam-A3.1-8) using a computer-assisted analysis of the mammaglobin-A protein sequence. Subsequently, we determined that CD8+ T cells from breast cancer patients reacted to peptides Mam-A3.1 (23-31, PLLENVISK), Mam-A3.3 (2-10, KLLMVLMLA), Mam-A3.4 (55-63, TTNAIDELK) and Mam-A3.8 (58-66, AIDELKECF) using an IFN-gamma enzyme-linked immunospot assay. A CD8+ T cell line generated in vitro against HLA-A*0301-transfected TAP-deficient T2 cells loaded with these peptides showed significant cytotoxic activity against the Mam-A3.1 peptide. This CD8+ T cell line showed a significant HLA-A3-restricted cytotoxic activity against mammaglobin-A-positive but not mammaglobin-A-negative breast cancer cells. In summary, our study identified four HLA-A3-restricted mammaglobin-A-derived epitopes naturally expressed by breast cancer cells, indicating the immunotherapeutic potential of this novel antigen for the treatment and prevention of breast cancer.
Topics: Breast Neoplasms; CD8-Positive T-Lymphocytes; Epitopes; Female; HLA-A3 Antigen; Humans; Immunodominant Epitopes; Mammaglobin A; Neoplasm Proteins; T-Lymphocytes, Cytotoxic; Tumor Cells, Cultured; Uteroglobin
PubMed: 12432553
DOI: 10.1002/ijc.10736 -
Breast Cancer Research and Treatment Feb 2013Mammaglobin-A (Mam-A) is a 10 kDa secretory protein that is overexpressed in 80 % of primary and metastatic human breast cancers. Previous studies from our laboratory...
Mammaglobin-A (Mam-A) is a 10 kDa secretory protein that is overexpressed in 80 % of primary and metastatic human breast cancers. Previous studies from our laboratory demonstrated that Mam-A cDNA vaccine can induce Mam-A-specific CD8 T cell responses and mediate regression of human breast cancer xenografts in NOD/SCID mice. In this article, we present our results on a phase I clinical trial of a Mam-A cDNA vaccination in breast cancer patients with stage-IV metastatic disease, including the impact of vaccination on the expression of the inducible co-stimulator molecule (ICOS) on CD4 T cells. Specimens from seven patients with stage-IV metastatic cancer were available for these analyses. Patients were vaccinated with a Mam-A cDNA vaccine on days 0, 28, and 56, and immune responses were assessed at serial time points following vaccination. At 6 months following the first vaccination, flow cytometric analysis demonstrated a significant increase in the frequency of CD4+ICOS(hi) T cells from 5 ± 2 % pre-vaccination to 23 ± 4 % (p < 0.001), with a concomitant decrease in the frequency of CD4+FoxP3+ T cells (regulatory T cells [Treg]) from 19 ± 6 to 10 ± 5 % (p < 0.05). ELISpot analysis of CD4+ICOS(hi) sorted T cells demonstrated that following vaccination the cytokines produced by Mam-A-specific T cells switched from IL-10 (78 ± 21 spm pre-vaccination to 32 ± 14 spm 5 months post-vaccine p < 0.001) to IFN-γ (12 ± 6 spm pre-vaccination to 124 ± 31 spm 5 months post-vaccine p < 0.001). The ratio of CD4+ICOS(hi) T cells to CD4+FoxP3+ T cells increased from 0.37 ± 0.12 before vaccination to 2.3 ± 0.72 (p = 0.021) following vaccination. Further, these activated CD4+ICOS(hi) T cells induced preferential lysis of human breast cancer cells expressing Mam-A protein. We conclude that Mam-A cDNA vaccination is associated with specific expansion and activation of CD4+ICOS(hi) T cells, with a concomitant decrease in Treg frequency. These encouraging results strongly suggest that Mam-A cDNA vaccination can induce antitumor immunity in breast cancer patients.
Topics: Breast Neoplasms; CD4-Positive T-Lymphocytes; Cancer Vaccines; DNA, Complementary; Female; Forkhead Transcription Factors; Humans; Inducible T-Cell Co-Stimulator Protein; Interferon-gamma; Interleukin-10; Lymphocyte Count; Mammaglobin A; T-Lymphocytes, Cytotoxic; Vaccines, DNA
PubMed: 22678162
DOI: 10.1007/s10549-012-2110-9 -
Cancer Cytopathology Apr 2014The usefulness of GATA3 (GATA-binding protein 3 to DNA sequence [A/T]GATA[A/G]) as a marker for metastatic breast carcinoma in serous effusion specimens was investigated. (Comparative Study)
Comparative Study
BACKGROUND
The usefulness of GATA3 (GATA-binding protein 3 to DNA sequence [A/T]GATA[A/G]) as a marker for metastatic breast carcinoma in serous effusion specimens was investigated.
METHODS
Cell block sections from 74 serous effusion specimens (32 ascitic, 2 pericardial, and 40 pleural fluids) were stained with an anti-GATA3 murine monoclonal antibody. The specimens included 62 confirmed metastatic carcinomas from the breast (30 specimens), female genital tract (13 specimens), gastrointestinal tract (7 specimens), lung adenocarcinoma (9 specimens), pancreas (1 specimen), kidney (1 specimen), and bladder (1 specimen). The breast carcinoma cases included 15 ductal carcinomas and 8 lobular carcinomas; the histology subtype was not available for 7 specimens. Twelve cases containing florid reactive mesothelial cells were also stained. The breast carcinoma cases were also stained for mammaglobin and gross cystic disease fluid protein of 15 kilodaltons (GCDFP-15) to compare their sensitivity with GATA3.
RESULTS
Positive nuclear staining for GATA3 was found to be present in 90% of metastatic breast carcinoma specimens (27 of 30 specimens). All nonbreast metastatic carcinomas tested were negative with the exception of the single case of metastatic urothelial carcinoma. No staining was observed in any of the benign reactive cases or in benign mesothelial cells present in the malignant cell block preparations. Two cases demonstrated weak positivity of benign lymphoid cells. Staining results were unambiguous because all positive cases demonstrated intense nuclear staining in > 50% of tumor cells. Mammaglobin (57% staining; 17 of 30 cases) and GCDFP-15 (33% staining; 10 of 30 cases) were found to be less sensitive markers of breast carcinoma. If used in a panel, mammaglobin and GCFP-15 staining would have identified only 1 additional case compared with those stained with GATA3.
CONCLUSIONS
GATA3 may be a useful addition to immunostaining panels for serous effusion specimens when metastatic breast carcinoma is a consideration.
Topics: Adult; Aged; Ascitic Fluid; Biomarkers, Tumor; Biopsy, Needle; Breast Neoplasms; Carrier Proteins; Diagnosis, Differential; Female; GATA3 Transcription Factor; Glycoproteins; Humans; Immunohistochemistry; Mammaglobin A; Membrane Transport Proteins; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Pericardial Effusion; Pleural Effusion, Malignant; Sampling Studies; Sensitivity and Specificity
PubMed: 24421220
DOI: 10.1002/cncy.21393 -
Human Immunology Jan 2012Human breast cancer-associated antigen, mammaglobin-A (Mam-A), potentially offers a novel therapeutic target as a breast cancer vaccine. In this study, we define the...
Human breast cancer-associated antigen, mammaglobin-A (Mam-A), potentially offers a novel therapeutic target as a breast cancer vaccine. In this study, we define the CD8(+) cytotoxic T lymphocyte (CTL) response to Mam-A-derived candidate epitopes presented in the context of HLA-A24 (A*2402). HLA-A24 has a frequency of 72% in Japanese, 27% in Asian Indian, and 18% in Caucasian populations. Using a human leukocyte antigen (HLA)-binding prediction algorithm we identified 7 HLA-A24-restricted Mam-A-derived candidate epitopes (MAA24.1-7). Membrane stabilization studies with TAP-deficient T2 cells transfected with HLA-A2402 (T2.A24) indicated that MAA24.2 (CYAGSGCPL) and MAA24.4 (ETLSNVEVF) have the highest HLA-A24 binding affinity. Further, 2 CD8(+) CTL cell lines generated in vitro against T2.A24 cells individually loaded with Mam-A-derived candidate epitopes demonstrated significant cytotoxic activity against MAA24.2 and MAA24.4. In addition, the same CD8(+) CTL lines lysed the HLA-A24(+)/Mam-A(+) stable transfected human breast cancer cell lines AU565 and MDA-MB-361. However, these CTLs had no cytotoxicity against HLA-A24(-)/Mam-A(+) and HLA-A24(+)/Mam-A(-) breast cancer cell lines. In summary, our results define HLA-A24-restricted, Mam-A-derived, CD8(+) CTL epitopes that can potentially be employed for Mam-A-based breast cancer vaccine therapy to breast cancer patients with HLA-A24 phenotype.
Topics: Amino Acid Sequence; Binding, Competitive; Breast Neoplasms; CD8 Antigens; Cancer Vaccines; Cell Line, Tumor; Cells, Cultured; Cytotoxicity, Immunologic; Epitope Mapping; Epitopes, T-Lymphocyte; Female; HLA-A24 Antigen; Humans; Mammaglobin A; Protein Binding; T-Lymphocytes, Cytotoxic; Transfection
PubMed: 22074997
DOI: 10.1016/j.humimm.2011.10.017