Association of hypoxia inducible factor-1 alpha and carbonic anhydrase IX overexpression and survival in HER2/neu positive hormone-unresponsive breast cancer patients

Abstract

e22078 Background: Hypoxia is common in solid tumors with overexpression of hypoxia inducible factor-1 alpha (HIF-1 alpha) and carbonic anhydrase IX (CA IX). In our study, we evaluated HIF-1alpha and CA IX expression in Her-2/neu positive hormone- unresponsive breast cancer patients. Methods: One hundred and eleven patients with operable breast cancer were identified who had paraffin-embedded tissue blocks available. Estrogen and progesterone receptors and Her-2/neu expression were evaluated by immunohistochemistry (IHC). FISH was used for IHC 2+ cases. We assigned two groups with 56 patients who have ER and PR receptor positive, Her-2/neu negative (group 1) and with 55 patients who have ER and PR negative, Her-2/neu positive (group 2). HIF 1 alpha and CA IX expressions were investigated and results were compared for both groups. Additionally, we investigated the association between HIF 1 alpha and CA IX expressions with stage, grade, lymph node metastasis, tumor dimension and menopause status. Results: Median age of the patients was 52 years (range, 34–77) in group 1 and 47 years (range, 27–83) in group 2. Nuclear HIF-1alpha expression was detected in 26 (46.4%) and 46 patients (83.6%) in group 1 and 2, respectively (p<0.0001). Membranous CA IX expression was detected in 25 (46.4%) and 37 (67.3%) patients in group 1 and 2, respectively (p<0.013). In group 1, median disease free survival (DFS) has not been reached. In group 2, median DFS was 46 months (95%CI: 42.98–49.02) (p= 0.0308). In group 1, median overall survival (OS) was 108 months (95%CI: 90.65–125.35) whereas in group 2, median OS was 75 months (95 % CI: 64.94- 85.06) (p= 0.0339). Conclusions: HIF-1 alpha and CA IX overexpressions were more frequently observed in ER and PR negative, Her-2/neu positive breast cancer. This was associated with shorter disease-free and overall survival. No significant financial relationships to disclose.