Differential expression of hyaluronan synthase 2 in breast carcinoma and its biological significance

Abstract

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.