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The hypoxia-inducible protein carbonic anhydrase IX is widely expressed in most human cancers, including breast carcinomas. CA IX attracts significant interest due to its strong association with neoplasms and its absence from corresponding normal tissues, suggesting its potential to serve as a promising diagnostic biomarker. This protein comes into the limelight also as a valuable prognostic and predictive parameter. Immunohistochemically, we examined the expression of this protein in 84 cases of invasive breast carcinoma to determinate the association with clinico-morphological and biological parameters such as age of patients, grade, stage and size of primary tumor, lymph node metastasis, vascular invasion as well as hormone receptor status and HER-2 expression. In each case, the subcellular localization of CA IX antigen, the intensity of staining and the percentage of labeled cells were assessed. Overall, CA IX was expressed in 34 cases (40.5%). The statistical analysis revealed a significant correlation between subcellular localization of CA IX and the age of patients. Furthermore, significant correlations were also found between the grade, estrogen and progesterone status and all immunohistochemical characteristics of CA IX expression (the subcellular localization of CA IX antigen, the intensity of staining and the percentage of labeled cells). We point out that mostly membrane or combined membrane and cytoplasmic positivity together with a higher intensity of CA IX immunoreactivity are associated with poor prognostic parameters, such as tumor grade 3 and also with negative estrogen and progesterone receptor status which may influence therapeutic approach. However, no significant correlations were shown with remaining clinico-morphological and biological parameters. We next investigate the relationship between CA IX expression in the group of invasive ductal carcinomas and the group of invasive lobular carcinomas and other less frequent types of breast carcinoma. There was, however, no significant difference. Our results suggest that moderate to strong membrane and combined membrane and cytoplasmic localization of CA IX may represent a valuable tumor biomarker as well as a promising prognostic and predictive parameter in invasive breast cancer.

Correlation of carbonic anhydrase IX expression with clinico-morphological parameters, hormonal receptor status and HER-2 expression in breast cancer