Relevance of cellular and serum carbonic anhydrase IX in primary breast cancer

Abstract

Carbonic anhydrase IX (CAIX) is involved in pH homeostasis, growth and survival of tumor cells. Besides the membranous form of CAIX, a soluble form is detectable in serum (s-CAIX). Overexpression of CAIX in tumors offers the opportunity for therapeutic strategies such as CAIX targeting antibodies. The aim of this study was to examine the relationships of CAIX mRNA expression and s-CAIX levels with clinicopathological parameters and survival of patients with primary breast cancer. Tumor tissue of 169 primary breast cancer patients was analyzed for RNA expression by microarray analysis (Affymetrix HG-U133A). Concentration of s-CAIX was determined by ELISA in blood samples of 140 patients. In tumor tissue, CAIX mRNA signal intensities (MAS5 values) ranged from 34 to 2,513. Higher CAIX expression was associated with younger age (</≥50 years p = 0.040), negative hormone receptors (estrogen receptor p = 0.004; progesterone receptor p = 0.022) and positive nodal status (p = 0.001) as well as with shorter disease-free survival (p = 0.031). Concentrations of s-CAIX ranged from 56 to 1,500 pg/ml. There was no correlation between s-CAIX and CAIX mRNA levels as well as clinicopathological characteristics or outcome. In contrast to reported immunohistochemical studies, we performed RNA-based tissue analyses of CAIX expression and, for the first time, analyzed CAIX serum levels in primary breast cancer. The correlations between CAIX RNA expression and prognostic factors and patient outcome support a biologic role of CAIX in early breast cancer. A role of s-CAIX in primary breast cancer is not supported by our findings.