Aims The important role of hyaluronan synthase 2 (HAS2), an isozyme responsible for hyaluronan synthesis, in cancer has been increasingly recognised. However, only a few studies with inconsistent results have been reported in breast cancers. With a large cohort, we aim to determine the clinical significance of HAS2 in breast cancers.
Methods We examined HAS2 expression in 1142 breast cancers using immunohistochemistry.
Results HAS2 was associated with both prognostically favourable (androgen receptor (AR), p<0.001) and unfavourable (basal and epithelial mesenchymal transition markers, p≤0.039) biomarkers. In addition, HAS2 showed differential associations with various features and outcome between AR+ and AR− subgroups. HAS2+AR− breast cancers showed significantly worse outcome than other subgroups, and HAS2+AR− subgroup was an independent adverse prognostic factor for disease-free survival (HR 1.309, p=0.046). Interestingly, HAS2 was associated with many poor prognostic features (including higher grade, lymphovascular invasion, basal-like breast cancer subtype, high Ki67 and basal marker expression) only in AR−, but not AR+ breast cancers.
Conclusions HAS2 has been proposed to be a target for therapeutic intervention in cancer. Our findings suggested a possible antagonistic role of AR pathway on HAS2 function. It will be interesting to further investigate their precise interaction, which may have important implication in HAS2 targeting.
- BREAST CANCER
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Handling editor Cheok Soon Lee
Contributors HZ performed the experiments, collected the data and wrote the paper. JYST analysed the data and wrote the paper. Y-BN, S-KC, K-FC and S-YC collected and arranged clinicopathological data of cases. GMT conceived the idea for the paper, provided guidance and critically revised the paper. All authors read and approved the final version to be published.
Competing interests None declared.
Ethics approval Joint Chinese University of Hong Kong—New Territories East Cluster clinical research ethics committee.
Provenance and peer review Not commissioned; externally peer reviewed.