Lien Huang-Chun, Lee Yi-Hsuan, Jeng Yung-Ming, Lin Ching-Hung, Lu Yen-Shen, Yao Yu-Tung
Department of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Histopathology. 2014 Sep;65(3):328-39. doi: 10.1111/his.12390. Epub 2014 Apr 2.
Hyaluronan synthase 2 (HAS2) is an enzyme in hyaluronan synthesis. Several studies have demonstrated that HAS2 plays a critical role in tumour progression in breast cancer cells. The in-situ expression patterns of HAS2 remain unclear, and the aim of this study was to determine these in order to elucidate the role of HAS2 in breast cancer.
We examined HAS2 expression using immunohistochemistry in 244 breast carcinomas of various subtypes. We found expression of HAS2 in 30.6% of invasive ductal carcinomas (IDCs); in IDCs, HAS2 expression was correlated significantly with the triple-negative phenotype and the basal-like phenotype, and univariate and multivariate analyses indicated that it was associated with poorer overall survival. In contrast to other carcinoma subtypes, HAS2 expression was observed in up to 72.7% of metaplastic carcinomas of breast (MCB), a carcinoma subtype related to the epithelial-mesenchymal transition (EMT). Consistently, we noted up-regulated levels of HAS2 RNA and protein in TGF-β-induced EMT in MCF-10A mammary epithelial cells.
Our findings demonstrate that HAS2 plays a role in aggressive phenotypes of primary breast carcinoma. The strong expression of HAS2 in MCB and the up-regulation of HAS2 in breast cells induced to exhibit EMT implicates an association between HAS2 expression and EMT in breast cancer.
透明质酸合酶2（HAS2）是透明质酸合成中的一种酶。多项研究表明，HAS2在乳腺癌细胞的肿瘤进展中起关键作用。HAS2的原位表达模式尚不清楚，本研究的目的是确定这些模式，以阐明HAS2在乳腺癌中的作用。
我们采用免疫组织化学方法检测了244例不同亚型乳腺癌中HAS2的表达。我们发现30.6%的浸润性导管癌（IDC）中有HAS2表达；在IDC中，HAS2表达与三阴性表型和基底样表型显著相关，单因素和多因素分析表明，它与较差的总生存率相关。与其他癌亚型不同，在高达72.7%的乳腺化生性癌（MCB）中观察到HAS2表达，MCB是一种与上皮-间质转化（EMT）相关的癌亚型。一致地，我们注意到在TGF-β诱导的MCF-10A乳腺上皮细胞EMT中，HAS2 RNA和蛋白水平上调。
我们的研究结果表明，HAS2在原发性乳腺癌的侵袭性表型中起作用。HAS2在MCB中的强表达以及在诱导表现出EMT的乳腺细胞中HAS2的上调表明HAS2表达与乳腺癌中的EMT之间存在关联。
