Breast-specific expression of MGB1/mammaglobin: an examination of 480 tumors from various organs and clinicopathological analysis of MGB1-positive breast cancers. Mod Pathol

Aichi Cancer Center, Ōsaka, Ōsaka, Japan
Modern Pathology (Impact Factor: 6.19). 03/2007; 20(2):208-14. DOI: 10.1038/modpathol.3800731
Source: PubMed


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.

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Available from: Yutaka Hatanaka, Apr 08, 2014
    • "Human mammaglobins A and B are homologues and members of a large family, and subsequently have been repeatedly reported as potentially valuable in breast cancer diagnosis and prognosis1415161718. Nevertheless, hMAG-B subtypes (hMAG B-1 and B-2) have also been detected in endometrioid endometrial carcinoma especially in well- and moderately-differentiated tumours1920212223, and hMAG A was also detected in a case of a poorly differentiated myoepithelial cell rich carcinoma, though this may have been of breast origin24. The nomenclature used in the literature shows various other names and abbreviations for mammaglobin variants and their genes, such as MAM, MGB, UGB3, MMG, SCGB2A1. "
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    ABSTRACT: 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.
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    • "For tumor diagnosis, primary location, morphology, histology and cytology, as well as clinical data, are crucial. According to the literature, the sensitivity and specificity of MAG and GCDFP-15 for the detection of breast cancer vary significantly, with MAG sensitivity being 80% to 48%, and that of GCDFP-15 being 73% to 23% [9,13,15]. In our study, MAG sensitivity was 34%, and its specificity 83%, while the sensitivity and specificity of GCDFP-15 were 44% and 79%, respectively. "
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    ABSTRACT: After skin cancer, breast cancer is the most common malignancy in women. Tumors of unknown origin account for 5-15% of malignant neoplasms, with 1.5% being breast cancer. An immunohistochemical panel with conventional and newer markers, such as mammaglobin, was selected for the detection of neoplastic cells of breast origin. The specific objectives are: 1) to determine the sensitivity and specificity of the panel, with a special emphasis on the inclusion of the mammaglobin marker, and 2) to compare immunohistochemistry performed on whole tissue sections and on Tissue Micro-Array. Twenty-nine metastatic breast tumors were included and assumed as tumors of unknown origin. Other 48 biopsies of diverse tissues were selected and assumed as negative controls. Tissue Micro-Array was performed. Immunohistochemistry for mammaglobin, gross cystic disease fluid protein-15, estrogen receptor, progesterone receptor and cytokeratin 7 was done. Mammaglobin positive staining was observed in 10/29 cases, in 13/29 cases for gross cystic disease fluid protein-15, in 20/29 cases for estrogen receptor, in 9/29 cases for progesterone receptor, and in 25/29 cases for cytokeratin 7. Among the negative controls, mammaglobin was positive in 2/48, and gross cystic disease fluid protein-15 in 4/48. The inclusion of MAG antibody in the immunohistochemical panel for the detection of tumors of unknown origin contributed to the detection of metastasis of breast cancer. The diagnostic strategy with the highest positive predictive value (88%) included hormone receptors and mammaglobin in serial manner. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here:
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    • "The authors investigated the presence of breast cancer cells by histology and immunohistochemistry in more than 160 ovarian cortex biopsies originating from 133 women entering the fertility preservation program. One of these studies [17] focused on gross cystic disease fluid protein-15 (GCDFP15) and mammaglobin-1 (MGB-1), two specific markers of breast epithelium that are not normally expressed in ovarian tissue [18] [19] [20]. In two additional studies, the authors used broad spectrum cytokeratin (CK) antibodies [15] or CK-7, CKaecam and markers of ovarian epithelium [16]. "
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