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Diagnostic Cytopathology Mar 2006Papillary carcinoma of the male breast is very rare. In this case report, we describe the cytologic, histologic, immunohistochemical, and radiological findings of a... (Review)
Review
Papillary carcinoma of the breast in a male patient with a treated prostatic carcinoma diagnosed by fine-needle aspiration biopsy: a case report and review of the literature.
Papillary carcinoma of the male breast is very rare. In this case report, we describe the cytologic, histologic, immunohistochemical, and radiological findings of a papillary carcinoma of male breast. A 67-yr-old man, who had a previous history of prostatic adenocarcinoma, presented with a retroareolar painless mass. There was no known history of breast cancer in his family. A fine-needle aspiration biopsy (FNAB) was performed. Cytological examination revealed a cellular aspirate with three-dimensional papillary clusters. A diagnosis of papillary lesion favoring papillary carcinoma was rendered. Immunohistochemical staining of the cell-block of the FNAB revealed the presence of mammaglobin, and the absence of prostatic specific antigen. The patient underwent lumpectomy, which showed a moderately differentiated infiltrating papillary carcinoma with adjacent areas of ductal carcinoma in situ. FNAB is a useful technique in identifying male breast carcinoma. In conjunction with ancillary studies, this procedure can effectively differentiate between a primary versus metastatic lesion.
Topics: Adenocarcinoma; Aged; Biopsy, Fine-Needle; Breast Neoplasms, Male; Carcinoma, Papillary; Diagnosis, Differential; Humans; Immunohistochemistry; Male; Mammaglobin A; Neoplasm Metastasis; Neoplasm Proteins; Neoplasms, Second Primary; Prostate-Specific Antigen; Prostatic Neoplasms; Uteroglobin
PubMed: 16548002
DOI: 10.1002/dc.20402 -
Thorax Mar 2006
Topics: Gene Expression; Humans; Mammaglobin A; Mesothelioma; Neoplasm Proteins; Pleural Effusion; Pleural Neoplasms; Uteroglobin
PubMed: 16517588
DOI: 10.1136/thx.2005.049270 -
Cancer Mar 2006Methods for identifying sentinel lymph nodes (SNs) and their clinical significance have been established. Recent advances in molecular immunology have enabled the...
BACKGROUND
Methods for identifying sentinel lymph nodes (SNs) and their clinical significance have been established. Recent advances in molecular immunology have enabled the analysis of precise immune responses. The objective of the current study was to clarify the dendritic cell (DC) maturation, T-helper type 1 (Th-1) and Th-2 responses, and regulatory T-cell responses of SNs in patients with breast carcinoma.
METHODS
SNs and non-SNs were identified by radioguided and blue dye-guided methods in 70 consecutive patients with clinically lymph node negative (N0) breast carcinoma. Lymphocytes were collected from SNs and non-SNs and were subjected to flow cytometric analysis (FCM) using antibodies of CD83-fluorescein isothiocyanate (FITC), CD80-phycoerythrin (PE), CD86-PE, CD40-PE, human leukemic D-related antigen (HLA-DR)-FITC, CD4-FITC, and CD25-PE. Total RNA was extracted from SNs and non-SNs, and the expression of CD83, interleukin 12p40 (IL-12p40), interferon gamma (IFN-gamma), IL-4, IL-10, and Foxp3 was evaluated by using quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. The immunologic status of SNs was analyzed further with regard to micrometastases, which were identified as negative microscopically but positive according to an RT-PCR analysis that was specific for mammaglobin.
RESULTS
SNs were detectable in 70 of 71 consecutive patients (98.6%) with clinically N0 breast carcinoma. Fourteen of 70 patients (20.0%) had positive metastasis in SNs. When SNs were compared with non-SNs in 56 metastasis-negative patients, FCM revealed that HLA-DR-positive, CD80-positive, CD86-positive, and CD40-positive cell populations were decreased significantly in SNs. RT-PCR analysis demonstrated that, among 44 patients with metastasis-negative SNs, the expression levels of CD83 and IFN-gamma mRNA were significantly lower in SNs compared with non-SNs. Immunologic parameters also were compared between 44 metastasis-negative SNs and 14 metastasis-positive SNs. The metastasis-positive SNs demonstrated significantly higher expression of CD83, IL-12p40, IFN-gamma, IL-10, and Foxp3 mRNA than the metastasis-negative SNs. Correction of micrometastasis detected by mammaglobin enhanced these differences consistently.
CONCLUSIONS
In patients with breast carcinoma, cellular immune responses, from DC maturation to Th-1 responses, appeared to be less active in SNs compared with non-SNs before metastasis developed. Once metastasis was established in SNs, DC maturation was triggered and was followed by the up-regulation of Th-1 responses, which may reflect antigen-specific immune responses in SNs. Unlike DC maturation and Th-1 responses after metastasis in SNs, up-regulation of Th-2 and regulatory T-cell responses developed in parallel.
Topics: Adult; Aged; Antigens, CD; Biomarkers, Tumor; Breast Neoplasms; Dendritic Cells; Female; Flow Cytometry; Gene Expression Regulation, Neoplastic; Humans; Lymphatic Metastasis; Mammaglobin A; Middle Aged; Neoplasm Proteins; RNA, Messenger; RNA, Neoplasm; Reverse Transcriptase Polymerase Chain Reaction; Sentinel Lymph Node Biopsy; T-Lymphocytes, Regulatory; Th1 Cells; Th2 Cells; Uteroglobin
PubMed: 16475148
DOI: 10.1002/cncr.21729 -
British Journal of Cancer May 2005In cancer patients, the ability to detect disseminated tumour cells in peripheral blood or bone marrow could improve prognosis and consent both early detection of...
Effect of different cytokines on mammaglobin and maspin gene expression in normal leukocytes: possible relevance to the assays for the detection of micrometastatic breast cancer.
In cancer patients, the ability to detect disseminated tumour cells in peripheral blood or bone marrow could improve prognosis and consent both early detection of metastatic disease and monitoring of the efficacy of systemic therapy. These objectives remain elusive mainly due to the lack of specific genetic markers for solid tumours. The use of surrogate tissue-specific markers can reduce the specificity of the assays and give rise to a clinically unacceptable false-positive rate. Mammaglobin (MAM) and maspin are two putative breast tissue-specific markers frequently used for detection of occult tumour cells in the peripheral blood, bone marrow and lymph nodes of breast cancer patients. In this study, it was evaluated whether MAM and maspin gene expression may be induced in the normal blood and bone marrow cells exposed to a panel of cytokines, including chemotactic factors (C5a, interleukin (IL)-8), LPS, proinflammatory cytokines (TNF-alpha, IL-1beta) and growth factors (IL-3, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor). The experimental data show that all cytokines included in the panel, except for IL-8, were able to induce maspin expression; on the contrary, MAM gene was never induced. These results suggest that MAM is more specific than maspin and that the possible interference of cytokines should be taken into account in interpreting molecular assays for detection of isolated tumour cells.
Topics: Biomarkers, Tumor; Breast Neoplasms; Cytokines; False Positive Reactions; Gene Expression Regulation; Genes, Tumor Suppressor; Humans; Mammaglobin A; Neoplasm Metastasis; Neoplasm Proteins; Neoplastic Cells, Circulating; Reverse Transcriptase Polymerase Chain Reaction; Sensitivity and Specificity; Serpins; Tumor Cells, Cultured; Uteroglobin
PubMed: 15841077
DOI: 10.1038/sj.bjc.6602563 -
Cancer Dec 2004The most common causes of malignant pleural effusions in women are metastatic lung carcinomas and breast carcinomas. It is often very difficult to distinguish between...
Mammaglobin and CRxA-01 in pleural effusion cytology: potential utility of distinguishing metastatic breast carcinomas from other cytokeratin 7-positive/cytokeratin 20-negative carcinomas.
BACKGROUND
The most common causes of malignant pleural effusions in women are metastatic lung carcinomas and breast carcinomas. It is often very difficult to distinguish between breast carcinomas and other metastatic carcinomas when they share a similar morphology and a similar cytokeratin profile (CK7-positive/CK20-negative [CK7+/CK20-]). To better differentiate between metastatic mammary carcinomas and other metastatic carcinomas in pleural effusion cytology, the authors studied the potential use of a novel antibody, CRxA-01, which was identified by a cDNA subtraction library, together with a well characterized antibody against mammaglobin.
METHODS
A computer search for patients with malignant pleural effusion specimens between January 1992 and November 2002 generated 228 patients, 71 of whom had cell block material and a known clinical history. Primary malignancies among these patients included 20 breast carcinomas, 32 lung carcinomas, 4 endometrial carcinomas, 9 ovarian carcinomas, 4 gastrointestinal carcinomas, and 2 genitourinary carcinomas. All specimens were immunostained with anti-CK7, CK20, CRxA-01, and mammaglobin antibodies. Only CK7-positive/CK20-negative (CK7+/CK20-) specimens were included in the current study, and only definitive membranous staining for CRxA-01 and cytoplasmic staining for mammaglobin were considered to be positive.
RESULTS
For patients with metastatic breast carcinomas, mammaglobin was positive in 11 of 20 (55%) tissue specimens and CRxA-01 was positive in 12 of 20 (60%) tissue specimens. When CRxA-01 and mammaglobin were used together, 16 of 20 (80%) tissue specimens were positive for mammaglobin or/and CRxA-01 antibodies. This staining pattern was not seen for tissue specimens from patients with other metastatic carcinomas. Two of 4 (50%) uterine carcinoma specimens and 6 of 9 (67%) ovarian carcinoma specimens were positive for CRxA-01 only.
CONCLUSIONS
CRxA-01 and mammaglobin were expressed in most metastatic breast carcinoma specimens. Other CK7+/CK20- carcinoma specimens did not express mammaglobin and showed weak or negative staining for CRxA-01. When used together, CRxA-01 and mammaglobin greatly improved the sensitivity and specificity for the detection of metastatic breast carcinoma in pleural effusion specimens.
Topics: Antibodies, Neoplasm; Biomarkers, Tumor; Breast Neoplasms; Carcinoma; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Lung Neoplasms; Mammaglobin A; Neoplasm Metastasis; Neoplasm Proteins; Pleural Effusion; Sensitivity and Specificity; Uteroglobin
PubMed: 15558786
DOI: 10.1002/cncr.20627 -
British Journal of Cancer Nov 2004Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) is a technique with the potential of improving the quantification of disseminated epithelial cells... (Comparative Study)
Comparative Study
Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) is a technique with the potential of improving the quantification of disseminated epithelial cells (DEC) in haematological tissues due to its exquisite sensitivity. This sensitivity may lead to false positivity. Immunocytochemistry (ICC) is regarded as the standard methodology to diagnose DEC. In this study, detection with ICC was compared with quantitative real-time RT-PCR for CK-19 and mammaglobin (hMAM) mRNA in bone marrow (BM) of patients with metastatic breast cancer (MBC). Bone marrow was aspirated from 14 control patients and from 29 patients with MBC. Mononuclear cells (MNC) were isolated. Immunostaining was carried out with the Epimet kit. Quantitative PCR was performed on the ABI Prism 7700. The CK-19 and hMAM mRNA quantities were normalised against beta-Actin and calculated relative to a calibrator sample (relative gene expression). All controls were negative by ICC and for hMAM expression measured by RT-PCR, whereas the median RGE value for CK-19 was 0.57. For the MBC patients, the median RGE for hMAM was 0 and 10 out of 25 (40%) tested positive. Median RGE for CK-19 was 2.9 and 20 out of 25 (80%) tested positive. With ICC, the median value was 1 stained cell per sample, and 15 out of 24 (62%) samples were positive. A correlation was observed between CK-19 and hMAM expression (r=0.7; P=0.0003), and between hMAM expression and ICC (r=0.6; P=0.003). CK-19 expression and ICC (r=0.9; P<0.0001) showed the strongest correlation. Reverse transcriptase-polymerase chain reaction for CK-19 resulted in a higher number of positive BM samples of patients with MBC than ICC. Since an excellent correlation is observed between ICC and RT-PCR, and RT-PCR is probably more sensitive with the advantage of being less observer dependent and thus also more easy to automate, we consider our quantitative real-time RT-PCR method as validated for the detection of DEC in the bone marrow of breast cancer patients.
Topics: Biomarkers, Tumor; Bone Marrow Examination; Bone Marrow Neoplasms; Breast Neoplasms; Epithelial Cells; Female; Humans; Immunohistochemistry; Keratins; Mammaglobin A; Molecular Diagnostic Techniques; Neoplasm Proteins; RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction; Sensitivity and Specificity; Uteroglobin
PubMed: 15505629
DOI: 10.1038/sj.bjc.6602189 -
Molecular Therapy : the Journal of the... Oct 2004Expression of secretoglobin family 2A member 2 (SCGB2A2, also known as mammaglobin-1) has been detected in a high percentage of primary and metastatic breast tumors, to...
The human SCGB2A2 (mammaglobin-1) promoter/enhancer in a helper-dependent adenovirus vector directs high levels of transgene expression in mammary carcinoma cells but not in normal nonmammary cells.
Expression of secretoglobin family 2A member 2 (SCGB2A2, also known as mammaglobin-1) has been detected in a high percentage of primary and metastatic breast tumors, to a lesser extent in normal breast, but not in other normal tissues. Plasmid transfection studies in our lab and others, however, were unable to identify the genetic elements regulating this specificity. Here we demonstrate that a 25-kb DNA fragment derived from the human SCGB2A2 gene upstream of the protein coding sequence was highly active and preferentially expressed in breast cancer cells when introduced via a helper-dependent adenoviral (HDAd) vector. HDAd delivery was selected for its high cloning capacity, its high efficiency of gene transfer, and the absence of cis-acting viral sequences that can potentially interfere with specificity of the inserted promoters. A series of vectors with deletions in the 25-kb fragment was constructed to identify important regulatory regions of the SCGB2A2 promoter. We have determined that elements controlling the specificity of expression reside within the first 345 bp upstream of the coding sequence. In addition, we identified a strong enhancer several kilobases upstream of this minimal promoter. We suggest that the SCGB2A2 promoter/enhancer should be particularly advantageous for gene therapy protocols involving oncolytic viruses or toxic gene transfer via adenovectors to mammary tumors.
Topics: Adenoviridae; Animals; Base Pairing; Breast Neoplasms; Carcinoma; Cell Line, Tumor; Enhancer Elements, Genetic; Female; Gene Expression Regulation, Neoplastic; Genes, Reporter; Genetic Therapy; Genetic Vectors; Helper Viruses; Humans; Luciferases; Mammaglobin A; Mammary Neoplasms, Experimental; Mice; Mice, Transgenic; Molecular Sequence Data; Neoplasm Proteins; Promoter Regions, Genetic; Sequence Deletion; Uteroglobin
PubMed: 15451460
DOI: 10.1016/j.ymthe.2004.06.849 -
Clinical Chemistry Nov 2004The aim of this study was to examine the potential usefulness of a mammaglobin multigene reverse transcription-PCR (RT-PCR) assay and a mammaglobin sandwich ELISA as...
BACKGROUND
The aim of this study was to examine the potential usefulness of a mammaglobin multigene reverse transcription-PCR (RT-PCR) assay and a mammaglobin sandwich ELISA as diagnostic tools in breast cancer.
METHODS
We studied peripheral blood samples from 147 untreated Senegalese women with biopsy-confirmed breast cancer and gathered patient information regarding demographic, and clinical staging of disease. The samples were tested for mammaglobin and three breast cancer-associated gene transcripts by a multigene real-time RT-PCR assay and for serum mammaglobin protein by a sandwich ELISA assay.
RESULTS
In 77% of the breast cancer blood samples, a positive signal was obtained in the multigene RT-PCR assay detecting mammaglobin and three complementary transcribed genes. Fifty samples from healthy female donors tested negative. Significant correlations were found between mammaglobin protein in serum, presence of mammaglobin mRNA-expressing cells in blood, stage of disease, and tumor size. Circulating mammaglobin protein was detected in 68% of the breast cancer sera, and was increased in 38% in comparison with a mixed control population. The RT-PCR assay and the ELISA for mammaglobin produced a combined sensitivity of 84% and specificity of 97%.
CONCLUSION
The ELISA and RT-PCR for mammaglobin and mammaglobin-producing cells could be valuable tools for diagnosis and prognosis of breast cancer.
Topics: Adult; Aged; Biomarkers, Tumor; Breast Neoplasms; Cell Line, Tumor; Enzyme-Linked Immunosorbent Assay; Female; Humans; Mammaglobin A; Middle Aged; Neoplasm Proteins; Neoplasm Staging; Reference Values; Reverse Transcriptase Polymerase Chain Reaction; Sensitivity and Specificity; Uteroglobin
PubMed: 15375015
DOI: 10.1373/clinchem.2004.038687 -
The Journal of Molecular Diagnostics :... May 2004The risk of developing second primary cancers is increased in patients with breast cancer. The lung is one of the major target organs, and therefore a differential...
The risk of developing second primary cancers is increased in patients with breast cancer. The lung is one of the major target organs, and therefore a differential diagnosis between primary and metastatic cancers is required for the treatment of lung tumors in patients with a history of breast cancer. However, biopsy specimens frequently result in small, fragmented tissues containing only a few, degenerated cancer cells. We attempted to find a useful marker for differential diagnosis, using the online SAGE database. We selected three molecules, small breast epithelial mucin (SBEM), prostate epithelium-specific Ets transcription factor (PDEF), and mammaglobin (MGB1), as potential markers for breast cancer. SBEM and PDEF proved of no use for practical differential diagnosis because they are expressed in the normal bronchus. In contrast, expression of MGB1 was detected in all 22 primary breast cancers, but not in 22 normal lung tissues. Furthermore, all 12 metastatic breast cancers examined demonstrated positive MGB1 transcripts, whereas one of 48 primary lung adenocarcinomas expressed MGB1. This suggests that MGB1 can serve as a differential molecular marker. In practice, prospective examination, using the nine cases with a history of breast cancer, confirmed the usefulness of MGB1 in differential diagnosis.
Topics: Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Breast Neoplasms; Bronchi; Diagnosis, Differential; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Lung; Lung Neoplasms; Lymphatic Metastasis; Mammaglobin A; Mucins; Neoplasm Proteins; Prospective Studies; Proto-Oncogene Proteins c-ets; Transcription Factors; Uteroglobin
PubMed: 15096563
DOI: 10.1016/S1525-1578(10)60495-3 -
Archives of Pathology & Laboratory... Oct 2003Organ specificity is a desirable property of a tumor marker, especially in metastatic adenocarcinomas of unknown primary origin. Mammaglobin, a mammary-specific member...
CONTEXT
Organ specificity is a desirable property of a tumor marker, especially in metastatic adenocarcinomas of unknown primary origin. Mammaglobin, a mammary-specific member of the uteroglobin family, is known to be overexpressed in human breast cancer.
OBJECTIVE
We investigated mammaglobin A expression in metastatic carcinomas of lymph nodes from the breast and various other organs and its usefulness in identifying metastatic carcinoma of the breast. For comparative purposes, we also investigated BRST-1 and BRST-2 expression.
DESIGN
We produced recombinant mammaglobin and polyclonal antimammaglobin antibodies. Mammaglobin expression was analyzed by immunohistochemical staining using a tissue microarray and by reverse transcription-polymerase chain reaction in 210 carcinomas, including those of the breast (n = 70), lung (n = 30), stomach (n = 30), colorectum (n = 25), hepatobiliary tract (n = 20), urinary tract (n = 10), thyroid gland (n = 10), ovary and endometrium (n = 10), and salivary gland (n = 5).
RESULTS
Mammaglobin expression was observed in 59 cases (84.3%) of breast cancer and in 21 cases (15.0%) of nonbreast cancer. The BRST-1 and BRST-2 expression rates were 75.7% and 44.3% in breast cancer and 26.4% and 2.1% in nonbreast cancer, respectively. Mammaglobin is superior to BRST-1 for both specificity and sensitivity and is superior to BRST-2 for sensitivity.
CONCLUSION
Our data suggest that mammaglobin is one of the first relatively mammary-specific and mammary-sensitive markers. Mammaglobin and BRST-2 appear to represent useful markers for breast cancer and should be used as a component of panels evaluating tumors of unknown primary sites.
Topics: Biomarkers, Tumor; Breast Neoplasms; Carcinoma; Female; Gene Expression; Humans; Immunohistochemistry; Lymph Nodes; Lymphatic Metastasis; Mammaglobin A; Neoplasm Proteins; Reverse Transcriptase Polymerase Chain Reaction; Uteroglobin
PubMed: 14521461
DOI: 10.5858/2003-127-1330-MEILNI