Carbonic anhydrase enzymes II, VII, IX and XII in colorectal carcinomas.
OBJECTIVE
To investigate expression of four alpha-carbonic anhydrases (CAs) in colorectal carcinomas (CRC) and compare the results with patients' survival.


METHODS
Colorectal carcinoma samples from 539 CRC patients and control tissues were arranged as tissue microarrays and analyzed with antibodies against CA II, CA VII, CA IX, and CA XII. Intensity and extent of staining were both scored from 0 to 3 in each sample. These enzyme expression levels were then correlated to patients' survival and clinicopathological parameters, which were tumor differentiation grade and stage, site of tumor, patients' age, and gender. Kaplan-Meier analysis and Cox regression hazard ratio model were used to analyze survival data.


RESULTS
CA II and CA XII staining intensities correlated with patients' survival in that higher expression indicated poorer prognosis. In Cox regression analysis one unit increase in the CA II intensity increased the hazard ratio to 1.19 fold (CI: 1.04-1.37, P = 0.009). A significant correlation was also found when comparing CA XII staining intensity with survival of CRC patients (HR = 1.18, 95%CI: 1.01-1.38, P = 0.036). The extent of CA XII immunostaining did not correlate to the patients' survival (P = 0.242, Kaplan-Meier analysis). A significant interaction between age group and extent of the CA II staining was found. Increased extent of CA II had a significant hazard ratio among patients 65 years and older (1.42, 95%CI: 1.16-1.73, P = 0.0006). No correlations were found between CA VII (intensity P = 0.566, extent P = 0.495, Kaplan-Meier analysis), or CA IX (intensity P = 0.879, extent P = 0.315, Kaplan-Meier analysis) immunostaining results and survival, or the other parameters.


CONCLUSIONS
The present findings indicate that CA II and CA XII could be useful in predicting survival in CRC.
Pia Viikilä, Seppo Parkkila, School of Medicine, University of Tampere and Fimlab Ltd, Tampere University Hospital, 33014 Tampere, Finland.
Pia
P
Viikilä
Pia Viikilä, Seppo Parkkila, School of Medicine, University of Tampere and Fimlab Ltd, Tampere University Hospital, 33014 Tampere, Finland.
Antti J
AJ
Kivelä
Pia Viikilä, Seppo Parkkila, School of Medicine, University of Tampere and Fimlab Ltd, Tampere University Hospital, 33014 Tampere, Finland.
Harri
H
Mustonen
Pia Viikilä, Seppo Parkkila, School of Medicine, University of Tampere and Fimlab Ltd, Tampere University Hospital, 33014 Tampere, Finland.
Selja
S
Koskensalo
Pia Viikilä, Seppo Parkkila, School of Medicine, University of Tampere and Fimlab Ltd, Tampere University Hospital, 33014 Tampere, Finland.
Abdul
A
Waheed
Pia Viikilä, Seppo Parkkila, School of Medicine, University of Tampere and Fimlab Ltd, Tampere University Hospital, 33014 Tampere, Finland.
William S
WS
Sly
Pia Viikilä, Seppo Parkkila, School of Medicine, University of Tampere and Fimlab Ltd, Tampere University Hospital, 33014 Tampere, Finland.
Jaromir
J
Pastorek
Pia Viikilä, Seppo Parkkila, School of Medicine, University of Tampere and Fimlab Ltd, Tampere University Hospital, 33014 Tampere, Finland.
Silvia
S
Pastorekova
Pia Viikilä, Seppo Parkkila, School of Medicine, University of Tampere and Fimlab Ltd, Tampere University Hospital, 33014 Tampere, Finland.
Seppo
S
Parkkila
Pia Viikilä, Seppo Parkkila, School of Medicine, University of Tampere and Fimlab Ltd, Tampere University Hospital, 33014 Tampere, Finland.
Caj
C
Haglund
D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D024402:Carbonic Anhydrase II / Q000378:metabolism*; D000071231:Carbonic Anhydrase IX / Q000378:metabolism*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000401:mortality; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012044:Regression Analysis; D046888:Tissue Array Analysis; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D024402:Carbonic Anhydrase II; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; C477051:carbonic anhydrase VI; C477378:carbonic anhydrase XII
Biomarker; Carbonic anhydrase; Colorectal cancer; Immunohistochemistry; Prognosis; Survival
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