title: Hyaluronan synthase 2 is an adverse prognostic marker in androgen receptor-negative breast cancer.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pathology, Peking University First Hospital, Beijing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Julia Y S
authors.initials: JY
authors.lastname: Tsang
authors.affiliation: Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Yun-Bi
authors.initials: YB
authors.lastname: Ni
authors.affiliation: Department of Pathology, Kwong Wah Hospital, Hong Kong, Hong Kong.
authors.forename: Siu-Ki
authors.initials: SK
authors.lastname: Chan
authors.affiliation: Department of Pathology, Tuen Mun Hospital, Hong Kong, Hong Kong.
authors.forename: Kui-Fat
authors.initials: KF
authors.lastname: Chan
authors.affiliation: Department of Pathology, Tuen Mun Hospital, Hong Kong, Hong Kong.
authors.forename: Sai-Yin
authors.initials: SY
authors.lastname: Cheung
authors.affiliation: Department of Pathology, Peking University First Hospital, Beijing, China.
authors.forename: Gary M
authors.initials: GM
authors.lastname: Tse
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D015331:Cohort Studies; D018572:Disease-Free Survival; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006801:Humans; D000076002:Hyaluronan Synthases; D007150:Immunohistochemistry; D008875:Middle Aged; D011379:Prognosis; D011944:Receptors, Androgen / Q000378:metabolism; D055815:Young Adult
chemical_list: C410798:AR protein, human; D014408:Biomarkers, Tumor; D011944:Receptors, Androgen; D014453:Glucuronosyltransferase; C101754:HAS2 protein, human; D000076002:Hyaluronan Synthases
keywords: BREAST CANCER; IMMUNOCYTOCHEMISTRY; STAINING