| Cytoplasmic expression of the JM403 antigen GlcA-GlcNH3+ on heparan sulfate glycosaminoglycan in mammary carcinomas--a novel proliferative biomarker for breast cancers with high malignancy. | |
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MedLine Citation:
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PMID: 21046235 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The expressions of heparan sulfate glycosaminoglycans (HSGAGs) in breast carcinoma specimens from 60 patients were immunohistochemically investigated using monoclonal antibodies (mAbs) that recognized different epitopes of the glycan structure. Cytoplasmic expression of GlcA-GlcNH(3)(+) on HSGAG was detected in carcinomas at high frequency (58.3%) using mAb JM403, whereas it was almost undetectable in normal breast ducts. This cytoplasmic expression was confirmed using confocal laser scanning microscopy. The expression of JM403 antigen in invasive carcinomas significantly correlated with nuclear atypia score (p = 0.0004), mitotic counts score (p = 0.0018), nuclear grade (p = 0.0061) and the incidence of metastasis to axillary lymph nodes (p = 0.0061). Furthermore, its expression was significantly correlated with the Ki67-labeling index in 55 invasive carcinomas (p < 0.05) as well as in 26 non-invasive carcinomas (5 non-invasive carcinomas and 21 non-invasive carcinomas that were observed in individual invasive carcinomas) (p < 0.005). Interestingly, the JM403 antigen GlcA-GlcNH(3)(+) was also expressed in the cytoplasm of normal crypt epithelial cells where Ki67 protein was expressed in the cell nuclei in the proliferative compartment of the human small intestines. To date, HSGAGs have generally been found to exist on cell surface membranes and in extracellular matrices as components of HS proteoglycans, and the negatively-charged sulfated domains on HSGAGs are considered to be important for their functions. However, our present findings indicate that the cytoplasmic expression of the JM403 antigen GlcA-GlcNH(3)(+) on positively charged, non-sulfated HSGAG may be involved in cell proliferation and associated with increased degrees of malignancy. The unordinary carbohydrate antigen of GlcA-GlcNH(3)(+) on HSGAGs recognized by mAb JM403 may represent a novel proliferative biomarker for highly malignant mammary carcinomas. |
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Authors:
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Masahiro Fujii; Akiko Yusa; Yukihiro Yokoyama; Toshio Kokuryo; Nobuyuki Tsunoda; Koji Oda; Masato Nagino; Tsuyoshi Ishimaru; Yoshie Shimoyama; Hirotoshi Utsunomiya; Hiroji Iwata; Yoshiko Itoh; Johbu Itoh; Reiji Kannagi; Mamoru Kyogashima |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-11-03 |
Journal Detail:
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Title: Glycoconjugate journal Volume: 27 ISSN: 1573-4986 ISO Abbreviation: Glycoconj. J. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-12-16 Completed Date: 2011-04-18 Revised Date: 2012-10-12 |
Medline Journal Info:
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Nlm Unique ID: 8603310 Medline TA: Glycoconj J Country: United States |
Other Details:
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Languages: eng Pagination: 661-72 Citation Subset: IM |
Affiliation:
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Division of Molecular Pathology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Aged, 80 and over Antigens, Neoplasm / biosynthesis* Breast Neoplasms / metabolism*, pathology, ultrastructure Cell Proliferation Cytoplasm / metabolism* Female Heparan Sulfate Proteoglycans / biosynthesis* Humans Intestine, Small / cytology, metabolism Ki-67 Antigen / biosynthesis Mammary Glands, Human / metabolism Middle Aged Receptor, erbB-2 / biosynthesis Receptors, Estrogen / biosynthesis Receptors, Progesterone / biosynthesis Tumor Markers, Biological / biosynthesis* |
| Chemical | |
Reg. No./Substance:
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0/Antigens, Neoplasm; 0/Heparan Sulfate Proteoglycans; 0/Ki-67 Antigen; 0/Receptors, Estrogen; 0/Receptors, Progesterone; 0/Tumor Markers, Biological; EC 2.7.10.1/ERBB2 protein, human; EC 2.7.10.1/Receptor, erbB-2 |
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