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

摘要

Aims: 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.Methods and results: 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 analysesindicated 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-beta-induced EMT in MCF-10A mammary epithelial cells. Conclusion: 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.