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International Journal of Clinical and... 2009Identification of metastasis and occult micrometastases of breast cancer demands sensitive and specific diagnostic markers. In this study, we assessed the utility of a...
Identification of metastasis and occult micrometastases of breast cancer demands sensitive and specific diagnostic markers. In this study, we assessed the utility of a mouse monoclonal antibody to human mammaglobin for one such purpose. Immunohistochemical stains were performed on paraffin-embedded sections from a total of 284 cases, which consisted of primary breast invasive carcinomas (41 cases) with matched metastases to ipsilateral axillary lymph nodes, metastatic breast carcinoma to liver (1 case) and kidney (1 case), non-breast neoplasms (161 cases), and normal human tissues (39 cases). The results showed 31 of the 41 cases of primary breast cancer with axillary lymph node metastases were positive for mammaglobin (76%). In the meantime, we documented expression of mammaglobin in occasional cases of endometrial carcinoma (17%). Our data further validated that mammaglobin is a valuable diagnostic marker for metastatic carcinoma of breast origin, although endometrial carcinoma should be considered as a major differential diagnosis.
PubMed: 19158935
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 -
BMC Cancer Feb 2008We sought to examine the detection rate of cancer cells in peripheral blood (PBL) and in bone marrow (BM) using an established 7-gene marker panel and evaluated whether...
BACKGROUND
We sought to examine the detection rate of cancer cells in peripheral blood (PBL) and in bone marrow (BM) using an established 7-gene marker panel and evaluated whether there were any definable associations of any individual gene with traditional predictors of prognosis.
METHODS
Patients with T1-T3 primary breast cancer were enrolled into a prospective, multi-institutional cohort study. In this interim analysis 215 PBL and 177 BM samples were analyzed by multimarker, real-time RT-PCR analysis designed to detect circulating and disseminated breast cancer cells.
RESULTS
At a threshold of three standard deviations from the mean expression level of normal controls, 63% (136/215) of PBL and 11% (19/177) of BM samples were positive for at least one cancer-associated marker. Marker positivity in PBL demonstrated a statistically significant association with grade II-III (vs. grade I; p = 0.0083). Overexpression of the mammaglobin (mam) gene alone had a statistically significant association with high tumor grade (p = 0.0315), and showed a trend towards ER-negative tumors and a high risk category. There was no association between marker positivity in PBL and the pathologic (H&E) and/or molecular (RT-PCR) status of the axillary lymph nodes (ALN).
CONCLUSION
This study suggests that molecular detection of circulating cancer cells in PBL detected by RT-PCR is associated with high tumor grade and specifically that overexpression of the mam gene in PBL may be a poor prognostic indicator. There was no statistically significant association between overexpression of cancer-associated genes in PBL and ALN status, supporting the concept of two potentially separate metastatic pathways.
Topics: Adult; Aged; Aged, 80 and over; Bone Marrow Cells; Breast Neoplasms; Cohort Studies; Female; Humans; Lymph Nodes; Mammaglobin A; Middle Aged; Neoplasm Proteins; Predictive Value of Tests; Prognosis; Prospective Studies; RNA, Messenger; Uteroglobin
PubMed: 18289390
DOI: 10.1186/1471-2407-8-55 -
Archives of Pathology & Laboratory... Feb 2008The lung is the most common site of metastasis during the natural history of malignant tumors. Breast carcinoma has a propensity for distant metastasis, and the lung and...
CONTEXT
The lung is the most common site of metastasis during the natural history of malignant tumors. Breast carcinoma has a propensity for distant metastasis, and the lung and pleura are among the most common metastatic sites. Although it is often difficult to make a clear-cut differential diagnosis between the two, distinguishing primary lung carcinoma from breast carcinoma metastatic to the lung is important because the treatment modalities are different.
OBJECTIVE
To elucidate the utility of mammaglobin and gross cystic disease fluid protein 15 (GCDFP-15), which are known to be breast-specific antigens, in distinguishing various primary lung and pleural tumors from breast carcinoma metastasizing to the lung.
DESIGN
A total of 20 cases of breast carcinoma metastatic to the lung and 263 tumors of nonbreast origin located in the lung and pleura were analyzed.
RESULTS
Of the 20 cases of breast carcinoma metastatic to the lung, 10 (50.0%) were immunoreactive for mammaglobin and 9 (45.0%) for GCDFP-15, the frequency of positivity being slightly higher for the former than for the latter. The area immunopositive for mammaglobin showed more diffuse staining than the area immunopositive for GCDFP-15. Furthermore, the specificity of mammaglobin for breast carcinoma metastatic to the lung was superior (98.9%) to that of GCDFP-15 (91.8%).
CONCLUSION
The sensitivity of mammaglobin is equal or superior to that of GCDFP-15 for investigation of breast carcinoma. Immunopositivity for mammaglobin is more diffuse than that for GCDFP-15. In terms of practical diagnosis, mammaglobin immunohistochemistry can serve as a differential marker of breast carcinoma and should be added to the immunohistochemical panel.
Topics: Biomarkers, Tumor; Breast Neoplasms; Carrier Proteins; Female; Fluorescent Antibody Technique, Direct; Glycoproteins; Humans; Immunoenzyme Techniques; Lung Neoplasms; Mammaglobin A; Membrane Transport Proteins; Neoplasm Proteins; Pleural Neoplasms; Sensitivity and Specificity; Uteroglobin
PubMed: 18251583
DOI: 10.5858/2008-132-239-AOEPOB -
Modern Pathology : An Official Journal... Feb 2007Previously, we used the reverse transcription-polymerase chain reaction (RT-PCR) to show that mammaglobin (MGB1) can serve as a differential marker of breast cancer...
Previously, we used the reverse transcription-polymerase chain reaction (RT-PCR) to show that mammaglobin (MGB1) can serve as a differential marker of breast cancer metastasis from primary lung cancer. However, mRNA-based methods are not appropriate for use in clinical practices. In this study, we examined MGB1 protein expression in 480 tumors from various organs using immunohistochemical detection and a tissue microarray technique. Breast cancers expressing MGB1 were also analyzed clinicopathologically to determine whether these cancers constitute a characteristic subset. Immunohistochemically, MGB1 was expressed specifically in breast cancers. Of the other cancers examined, including 29 of the head and neck, eight of the thyroid, 106 of the lung, 35 of the gastrointestinal tract, three of the pancreas, 14 of the uterine cervix and 13 of the ovary, none were positive for MGB1 except a proportion of salivary gland tumors (6/11, 55%) and endometrial cancers (3/23, 13%). Among the 238 breast cancers, MGB1 was expressed in 114 (48%), most of which were classified histologically as invasive duct or lobular carcinomas. Clinicopathologically, MGB1 expression was associated with positive expression of estrogen receptors and negative expression of CK5, but not with pathological stage, HER2 gene amplification or p53 immunoreactivity. Kaplan-Meier analysis revealed prolonged disease-free survival in patients with MGB1-positive breast cancers (log rank test, P=0.016), but the Cox proportional hazard model failed to confirm that MGB1 was an independent prognostic factor (hazard ratio 1.77, P=0.1755). In terms of practical diagnosis, MGB1 immunohistochemistry can serve as a differential marker of breast cancer metastasis from primary lung cancer for two reasons. Firstly, HER2-positive breast cancer frequently lacks estrogen receptor expression, but MGB1 is expressed in about half of this subtype. Secondly, as primary lung adenocarcinomas may express estrogen receptors, MGB1 expression provides further discrimination of the origin of breast cancers.
Topics: Adenocarcinoma; Biomarkers, Tumor; Breast Neoplasms; Cell Count; Diagnosis, Differential; Disease-Free Survival; Female; Humans; Immunoenzyme Techniques; Japan; Lung Neoplasms; Mammaglobin A; Neoplasm Proteins; Neoplasm Staging; Receptors, Estrogen; Survival Rate; Tissue Array Analysis; Uteroglobin
PubMed: 17192791
DOI: 10.1038/modpathol.3800731 -
Anticancer Research 2006The expressions of three mRNA markers were correlated with the results of extensive histopathological examination of a total of 290 axillary lymph nodes from 29 breast...
The expressions of three mRNA markers were correlated with the results of extensive histopathological examination of a total of 290 axillary lymph nodes from 29 breast carcinoma patients. Included were two established markers for breast cancer (cytokeratin-19 and mammaglobin) and the novel marker DNA methyltransferase 3b (DNMT3b). DNMT3b was significantly overexpressed in breast cancer compared to normal breast tissue. The expression of the three markers in axillary lymph nodes was determined using quantitative real-time RT-PCR. DNMT3b expression showed a specificity of more than 99%, which was comparable to that of cytokeratin-19 and better than that of mammaglobin. The sensitivity of RT-PCR relative to histopathology was highest for cytokeratin-19 (96%), followed by DNMT3b (88%) and mammaglobin (68%). The overall agreement of histological and RT-PCR results was 96-99%. The results indicate that expression analysis of marker genes by quantitative RT-PCR can be a useful tool for lymph node diagnosis in breast cancer.
Topics: Base Sequence; Breast Neoplasms; DNA (Cytosine-5-)-Methyltransferases; DNA Primers; Humans; Keratin-19; Lymphatic Metastasis; Mammaglobin A; Neoplasm Proteins; RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction; Uteroglobin; DNA Methyltransferase 3B
PubMed: 17094413
DOI: No ID Found -
Asian Pacific Journal of Cancer... 2006As many as 30% of node-negative breast cancer patients relapse within five years, suggesting that current histological detection methods are inadequate for identifying... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
As many as 30% of node-negative breast cancer patients relapse within five years, suggesting that current histological detection methods are inadequate for identifying metastatic disease. Detecting small number of cancer cells in the breast tissue or lymph node by reverse transcription-polymerase chain reaction (RT-PCR) assays using a combination of tissue and cancer specific markers might be very useful in the early detection or monitoring of the treatment. Mammaglobin is a member of the uteroglobin gene family and appears to be expressed only in breast tissue. Carcinoembryonic antigen has been the preferred molecular marker for detection of micro metastases in lymph nodes in almost all carcinomas.
MATERIALS AND METHODS
Samples were collected from randomly chosen breast cancer patients undergoing modified mastectomy or breast conserving surgery between September 2003 and July 2004. RT-PCR was applied to study the expression of MMG and CEA markers. Breast cancer micrometastases in axillary lymph nodes were also assessed.
RESULTS
The MMG marker was positive in 9/10 normal breast tissues, 3/3 breast fibroadenomas and 37/39 of breast carcinoma tissues, giving an overall sensitivity of 94%. The sensitivity was 80% for metastatic lymph node samples. On the other hand CEA showed 95% sensitivity for malignant breast tumors and 100% sensitivity for metastatic lymph nodes.
CONCLUSIONS
RT-PCR using a combination of MMG and CEA markers is a powerful tool to complement current routine histopathology techniques for detection of breast cancer metastasis in axillary nodes.
Topics: Axilla; Biomarkers, Tumor; Breast Neoplasms; Carcinoembryonic Antigen; Early Diagnosis; Female; Fibroadenoma; Humans; Lymph Nodes; Lymphatic Metastasis; Mammaglobin A; Mastectomy; Neoplasm Proteins; RNA, Messenger; RNA, Neoplasm; Reverse Transcriptase Polymerase Chain Reaction; Sensitivity and Specificity; Uteroglobin
PubMed: 17059329
DOI: No ID Found -
The Journal of Molecular Diagnostics :... Jul 2006
Topics: Biomarkers, Tumor; Breast; Gene Expression; Humans; Lung; Lung Neoplasms; Mammaglobin A; Neoplasm Proteins; Uteroglobin
PubMed: 16831819
DOI: 10.2353/jmoldx.2006.050143 -
Annals of Oncology : Official Journal... Jun 2006Mammaglobin is expressed mainly in mammary tissue, overexpressed in breast cancer (BC) and rarely in other tissue. The aim of this study was to assess the sensitivity...
Detection and quantification of mammaglobin in the blood of breast cancer patients: can it be useful as a potential clinical marker? Preliminary results of a GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.
BACKGROUND
Mammaglobin is expressed mainly in mammary tissue, overexpressed in breast cancer (BC) and rarely in other tissue. The aim of this study was to assess the sensitivity and specificity of transcript MGB1 detection and to evaluate the role of MGB1 as potential clinical marker for the detection of disseminated cancer cells in the blood of BC patients.
PATIENTS AND METHODS
A consecutive series of 23 BC tissues, 36 peripheral blood BC samples and 35 healthy peripheral blood samples was prospectively recruited to investigate MGB1 expression by means of a quantitative Real Time RT-PCR assay.
RESULTS
MGB1 overexpression in tissue samples of BC patients is significantly associated only with high level of Ki67 (P <0.05). None of the samples from peripheral blood of 35 healthy female individuals were positive for MGB1 transcript. In contrast MGB1 mRNA expression was detected in three of 36 (8%) peripheral blood of BC patients.
CONCLUSIONS
Our preliminary results demonstrate that the detection of MGB1 transcript in peripheral blood of BC patients was specific but with low sensitivity. MGB1 overexpression by itself or in combination with Ki67 might be considered an index of BC progression.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Breast Neoplasms; Female; Humans; Mammaglobin A; Middle Aged; Neoplasm Proteins; Neoplastic Cells, Circulating; Prospective Studies; RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction; Sensitivity and Specificity; Uteroglobin
PubMed: 16760290
DOI: 10.1093/annonc/mdl948 -
BMC Cancer Apr 2006Mammaglobin A (SCGB2A2) and lipophilin B (SCGB1D2), two members of the secretoglobin superfamily, are known to be co-expressed in breast cancer, where their proteins...
Expression analysis of mammaglobin A (SCGB2A2) and lipophilin B (SCGB1D2) in more than 300 human tumors and matching normal tissues reveals their co-expression in gynecologic malignancies.
BACKGROUND
Mammaglobin A (SCGB2A2) and lipophilin B (SCGB1D2), two members of the secretoglobin superfamily, are known to be co-expressed in breast cancer, where their proteins form a covalent complex. Based on the relatively high tissue-specific expression pattern, it has been proposed that the mammaglobin A protein and/or its complex with lipophilin B could be used in breast cancer diagnosis and treatment. In view of these clinical implications, the aim of the present study was to analyze the expression of both genes in a large panel of human solid tumors (n = 309), corresponding normal tissues (n = 309) and cell lines (n = 11), in order to evaluate their tissue specific expression and co-expression pattern.
METHODS
For gene and protein expression analyses, northern blot, dot blot hybridization of matched tumor/normal arrays (cancer profiling arrays), quantitative RT-PCR, non-radioisotopic RNA in situ hybridization and immunohistochemistry were used.
RESULTS
Cancer profiling array data demonstrated that mammaglobin A and lipophilin B expression is not restricted to normal and malignant breast tissue. Both genes were abundantly expressed in tumors of the female genital tract, i.e. endometrial, ovarian and cervical cancer. In these four tissues the expression pattern of mammaglobin A and lipophilin B was highly concordant, with both genes being down-, up- or not regulated in the same tissue samples. In breast tissue, mammaglobin A expression was down-regulated in 49% and up-regulated in 12% of breast tumor specimens compared with matching normal tissues, while lipophilin B was down-regulated in 59% and up-regulated in 3% of cases. In endometrial tissue, expression of mammaglobin A and lipophilin B was clearly up-regulated in tumors (47% and 49% respectively). Both genes exhibited down-regulation in 22% of endometrial tumors. The only exceptions to this concordance of mammaglobin A/lipophilin B expression were normal and malignant tissues of prostate and kidney, where only lipophilin B was abundantly expressed and mammaglobin A was entirely absent. RNA in situ hybridization and immunohistochemistry confirmed expression of mammaglobin A on a cellular level in endometrial and cervical cancer and their corresponding normal tissues.
CONCLUSION
Altogether, these data suggest that expression of mammaglobin A and lipophilin B might be controlled in different tissues by the same regulatory transcriptional mechanisms. Diagnostic assays based on mammaglobin A expression and/or the mammaglobin A/lipophilin B complex appear to be less specific for breast cancer, but with a broader spectrum of potential applications, which includes gynecologic malignancies.
Topics: Biomarkers, Tumor; Blotting, Northern; Breast Neoplasms; Cell Line, Tumor; Endometrial Neoplasms; Female; Gene Expression; Gene Expression Profiling; Genital Neoplasms, Female; Humans; Immunohistochemistry; In Situ Hybridization; Mammaglobin A; Myelin Proteins; Neoplasm Proteins; Ovarian Neoplasms; Proteolipids; RNA, Neoplasm; Reverse Transcriptase Polymerase Chain Reaction; Secretoglobins; Uterine Cervical Neoplasms; Uteroglobin
PubMed: 16603086
DOI: 10.1186/1471-2407-6-88