Expressions of HIF-1α and CA9 in breast carcinoma and their relationships with basal-like subtype

Abstract

Objective To study the expressions of hypoxia inducible factor-1α (HIF-1α) and carbo-nic anhydrase 9 (CA9) in different molecular subtypes of breast carcinoma and their relationships with basal-like subtype. Methods The expressions of HIF-1α and CA9 were detected by immunohistochemistry in five subtypes of breast carcinoma (n=803). The relationships of the expressions of HIF-1α and CA9 with the clinicopathologic parameters of basal-like subtype and with the prognosis of patients were analyzed. Results The positive expression rates of HIF-1α and CA9 protein in breast carcinoma were much higher than those in para-tumor breast tissues (43.96% vs. 3.86%, χ2=354.858, P<0.001; 19.80% vs. 4.61%, χ2=86.495, P<0.001). The positive expression rates of HIF-1α in Luminal A, Luminal B, epidermal growth factor receptor-2 (HER-2) over-expression, basal-like and normal breast-like subtypes were 31.97%, 25.00%, 56.06%, 77.89% and 55.76% respectively, and the positive expression rates of CA9 were 7.48%, 5.56%, 60.61%, 40.00% and 27.88% respectively, with significant differences (χ2=88.628, P<0.001; χ2=147.128, P<0.001). The positive expression rates of HIF-1α and CA9 in estrogen receptor (ER)-negative breast carcinomas (HER-2 over-expression, basal-like and normal breast-like) were significantly higher than those in ER-positive subtypes (Luminal A and Luminal B, all P<0.005). There was a significant positive correlation between HIF-1α and CA9 (C=0.315, P=0.001), and both were correlated with the lymph node metastasis (χ2=4.542, P=0.033; χ2=7.025, P=0.008), pTNM stage (χ2=5.390, P=0.020; χ2=10.179, P=0.001) and poor prognosis (χ2=4.353, P=0.037; χ2=6.056, P=0.014) of basal-like subtype. Conclusion Over-expressions of HIF-1α and CA9 may be related to the ER-negative breast cancer more closely, and both may play important roles in the occurrence and development of basal-like subtype. Over-expressions of HIF-1α and CA9 may suggest the poorer prognosis of patients with basal-like breast carcinoma. Key words: Breast neoplasms; Hypoxia-inducible factor 1, alpha subunit; Carbonic anhydrases; Basal-like subtype