Prognostic Significance of Carbonic Anhydrase IX (CA-IX), Endoglin (CD105) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in Breast Cancer Patients

Abstract

The aim of this study was to examine the prognostic significance of carbonic anhydrase IX (CA-IX), an endogenous marker for tumor hypoxia; endoglin (CD105), a proliferation-associated and hypoxia-inducible glycoprotein and 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative DNA lesion, in breast cancer patients. Immunohistochemical expressions of CA-IX, CD105 and 8-OHdG, analyzed on paraffin-embedded tumor tissues from forty female breast cancer patients, were used to assess their prognostic implication on overall survival (OS) and relapse-free survival (RFS). Patients with high CA-IX expression (above cut-off value) had a higher occurrence of relapse (P = = 0.002). High CA-IX expression was significantly associated with shorter RFS (P < 0.001, hazard ratio (HR) 0.21) and shorter OS (P < 0.001, HR 0.19). Lymph node negative patients with high CA-IX expression had worse RFS (P = 0.031, HR 0.14) and OS (P = 0.005, HR 0.05). Patients with grade I&II tumors and high CA-IX expression showed shorter RFS (P = 0.028, HR 0.28) and OS (P = 0.008, HR 0.20). Worse OS (P = 0.046, HR 0.28) was found in subgroup of patients with grade II tumors and high CA-IX expression. Among all three markers, only high CA-IX expression was strong independent prognostic indicator for shorter OS (HR 4.14, 95% CI 1.28-13.35, P = 0.018) and shorter RFS (HR 3.99, 95% CI 1.38-11.59, P = 0.011). Elevated expression of CA-IX was an independent prognostic factor for decreased RFS and OS and a significant marker for tumor aggressiveness. CD105 had week prognostic value; whereas, 8-OHdG, in this study, did not provide sufficient evidence as a prognostic indicator in breast cancer patients.

Tumour oxygenation: implications for breast cancer prognosis

“…In breast cancer, abundant expression of CAIX and GLUT‐1 is associated with high‐grade cancers . CAIX has been linked to shorter relapse‐free survival in patients with grade I and II tumours and to poor prognosis in invasive breast carcinoma . CAIX has also been suggested as a predictive marker for response to chemotherapy and adjuvant treatment in patients with breast cancer .…”

Apoptosis regulator Bcl-2 is an independent prognostic marker for worse overall survival in triple-negative breast cancer patients

“…In our previous study we have shown that high expression of CAIX was a strong independent prognostic indicator for shorter OS and recurrence-free survival (RFS) for patients with invasive ductal breast carcinoma (18). The objective of this study was to examine the expression of the hypoxic marker CAIX relative to expressions of the apoptosis regulator Bcl-2, tumor suppressor protein p53 and proliferative index Ki-67, to examine the role of hypoxia in TNBC.…”

Prognostic relevance of carbonic anhydrase IX expression is distinct in various subtypes of breast cancer and its silencing suppresses self-renewal capacity of breast cancer cells

“…Furthermore, CAIX expression in cancers can be induced by the hypomethylation of the CA9 promoter or by inactivating mutations in the VHL gene that may drive the overexpression of CAIX independently of hypoxic conditions [12][13][14]. Most of the studies show that its overexpression in BC is a poor prognostic marker for distant metastasis and survival [15][16][17]; however, several other studies did not find a significant association with relapse-free or overall survival [18,19]. It seems likely that these contradictory findings at least partially may be explained by its differential expression in various subtypes of BC [16,20]; however, the prognostic significance of CAIX expression within the subtypes has not been systematically studied so far.…”