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
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
复制标题
乳腺癌中 JM403 抗原 GlcA-GlcNH3 在硫酸乙酰肝素糖胺聚糖上的细胞质表达 - 一种新型高度恶性乳腺癌增殖生物标志物
DOI：
10.1007/s10719-010-9311-4
复制
发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Kyogashima M
中科院分区：
文献类型：
--
作者：
Fujii M;Yusa A;Yokoyama Y;Kokuryo T;Tsunoda N;Oda K;Nagino M;Ishimaru T;Shimoyama Y;Utsunomiya H;Iwata H;Itoh Y;Itoh J;Kannagi R;Kyogashima M
应用识别不同糖链结构表位的单抗，对60例乳腺癌标本中硫酸乙酰肝素糖胺聚糖(HSGAGs)的表达进行了免疫组织化学研究。用JM403单抗检测到HSGAG上Glca-GlcNH3+的胞浆表达频率较高(58.3%)，而在正常乳腺导管中几乎检测不到。激光共聚焦扫描显微镜证实了这种细胞质的表达。JM403抗原在浸润性癌中的表达与核异型性评分(p= 0.0004)、核分裂计数评分(p= 0.0018)、核分级(p= 0.0061)和腋窝淋巴结转移率(p= 0.0061)显著相关。此外，在55例浸润性癌(p<； 0.005)和26例非浸润性癌(5例非浸润性癌和21例非浸润性癌)中，其表达与Ki67标记指数显著相关(p<； 0.05)。有趣的是，JM403抗原Glca-GlcNH3+也表达在正常隐窝上皮细胞的胞浆中，而Ki67蛋白表达在人小肠增生室的细胞核中。到目前为止，HSGAGs作为HS蛋白多糖的组成部分普遍存在于细胞表面膜和细胞外基质中，HSGAGs上的负电荷硫酸基结构域被认为是其功能的重要组成部分。然而，我们目前的发现表明，JM403抗原Glca-GlcNH3+在正电荷、非硫酸盐化的HSGAG上的胞浆表达可能与细胞增殖有关，并与恶性程度的增加有关。JM403单抗识别的HSGAGs上Glca-GlcNH3+的异常糖类抗原可能是高度恶性乳腺癌的一种新的增殖生物标志物。
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-GlcNH3+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-GlcNH3+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-GlcNH3+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-GlcNH3+on HSGAGs recognized by mAb JM403 may represent a novel proliferative biomarker for highly malignant mammary carcinomas.