Carbonic anhydrase IX is a clinically significant tissue and serum biomarker associated with renal cell carcinoma - PubMed (original) (raw)

doi: 10.3892/ol.2012.1001. Epub 2012 Oct 26.

Maria Bartosova, Lucia Skvarkova, Miriam Zatovicova, Ivana Vidlickova, Lucia Csaderova, Monika Barathova, Jan Breza Jr, Peter Bujdak, Jaromir Pastorek, Jan Breza Sr, Silvia Pastorekova

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Carbonic anhydrase IX is a clinically significant tissue and serum biomarker associated with renal cell carcinoma

Martina Takacova et al. Oncol Lett. 2013 Jan.

Abstract

Carbonic anhydrase IX (CA IX) is regarded as one of the most prominent markers of tumor hypoxia with potential to serve as a diagnostic biomarker, prognostic indicator as well as tumor therapeutic target. The aim of the present study was to perform an in-depth analysis of CA IX expression in blood and tissue samples and to evaluate the significance of CA IX status for different renal cell carcinomas (RCCs). The expression of CA IX was determined in blood and tissue samples from 74 kidney cancer patients using reverse transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), Western blotting (WB) and immunohistochemistry (IHC). The CA IX status was correlated with RCC type and tumor stage. IHC and WB provided evidence for a significantly higher expression of CA IX in clear cell RCC (CCRCC) specimens compared to other RCCs. RT-PCR assay revealed that 32.42% of all RCC patients possess CA9-positive cells in peripheral blood and three-quarters of CA9-positive patients were diagnosed with CCRCC. When the patients were subdivided according to tumor stage, decreased positivity was observed with higher tumor stage (50% in T1 vs. 17% in T3). Serum CA IX levels determined by ELISA were significantly higher in CCRCC patients than in non-CCRCC. A significant association between s-CA IX and CCRCC tumor stage was also determined (T1-87.51 vs. T3-341.98 pg/ml, p=0.046). We demonstrated that the CA IX expression profiles in blood and tissue samples from 74 kidney cancer patients are closely correlated with their histological subtypes. This is the first study reporting CA IX expression in blood and tissue samples from kidney cancer patients determined by four different methods.

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Figures

Figure 1

Figure 1

CA IX expression in RCC tissues analyzed by Western blotting. Expression of CA IX in the tumor tissues from various RCCs was analyzed by Western blotting using the specific monoclonal antibody M75. Tumor samples (T) containing a twin band (54 and 58 kDa) which represents the CA IX protein were marked as positive. Normal kidney tissue (K) showed a complete absence of CA IX. Anti-actin antibody was used as a loading control (42 kDa).

Figure 2

Figure 2

Correlation between circulating tumor cell detection and CA IX expression in tumor tissue. CCRCC patients were stratified according to tumor stage and detection of CA9 mRNA in peripheral blood samples using RT-PCR (x-axis) was compared with tissue CA IX quantification (in pg/100 _μ_g of total proteins) using ELISA (y-axis).

Figure 3

Figure 3

Immunohistochemical staining for CA IX expression in RCC tumor samples. Representative view of CA IX staining from (A,B and C) clear cell, (D) papillary and (E) chromophobe RCC as well as (F) oncocytoma.

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