The key hypoxia regulated gene CAIX is upregulated in basal-like breast tumours and is associated with resistance to chemotherapy

• DOI: 10.1038/sj.bjc.6604844
• Publication Date: 2009-01-22T23:52:46Z
• Authors: E Y Tan; M Yan; L Campo; C Han; E Takano; H Turley; I Candiloro; F Pezzella; K C Gatter; E K A Millar; S A O'Toole; C M McNeil; P Crea; D Segara; R L Sutherland; A L Harris; S B Fox
• Keywords: Basal (medicine); Nottingham Prognostic Index; Hypoxia

Basal-like tumours account for 15% of invasive breast carcinomas and are associated with a poorer prognosis resistance to therapy. We hypothesised that this aggressive phenotype is because an intrinsically elevated hypoxic response. Microarrayed from 188 patients were stained hypoxia-inducible factor (HIF)-1α, prolyl hydroxylase (PHD)1, PHD2, PHD3 inhibiting HIF (FIH)-1, carbonic anhydrase (CA) IX in 456 tumours. Tumour subtypes correlated standard clincopathological parameters as well markers. Out 62 (14%) basal-like. These positively high tumour grade (P<0.001) significantly worse disease-free survival compared luminal (P<0.001). Fifty percent basal-like expressed HIF-1α, more than half at least one the PHD enzymes FIH-1. nine times likely be CAIX expression multivariate analysis. Carbonic was size (P=0.005), oestrogen receptor (ER) negativity Patients any CAIX-positive basal group had CAIX-negative when treated chemotherapy (P<0.001 P=0.03, respectively). The association between suggests behaviour these partly due enhanced Further, chemoresistance particular raises possibility targeted therapy against pathway or downstream genes such CAs may approach investigate patients.