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.
Keywords: BREAST CANCER; IMMUNOCYTOCHEMISTRY; STAINING.
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