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©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
Carbonic anhydrase enzymes II, VII, IX and XII in colorectal carcinomas
Pia Viikilä, Antti J Kivelä, Harri Mustonen, Selja Koskensalo, Abdul Waheed, William S Sly, Jaromir Pastorek, Silvia Pastorekova, Seppo Parkkila, Caj Haglund
Pia Viikilä, Seppo Parkkila, School of Medicine, University of Tampere and Fimlab Ltd, Tampere University Hospital, 33014 Tampere, Finland
Antti J Kivelä, Harri Mustonen, Selja Koskensalo, Caj Haglund, Department of Surgery, University of Helsinki and Helsinki University Hospital, 00100 Helsinki, Finland
Abdul Waheed, William S Sly, Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO 63104, United States
Jaromir Pastorek, Silvia Pastorekova, Centre of Molecular Medicine, Institute of Virology, Slovak Academy of Sciences, 811 04 Bratislava, Slovak Republic
Caj Haglund, Research Programs Unit, Translational Cancer Biology, University of Helsinki, 00100 Helsinki, Finland
Author contributions: Viikilä P, Parkkila S, Kivelä AJ and Haglund C participated in the design of the study; Clinical and survival data were collected by Koskensalo S and Haglund C; Haglund C collected samples of this study and constructed tissue microarrays; Immunohistochemical staining and light microscopy was performed by Viikilä P; Waheed A, Sly WS, Pastorek J, Pastorekova S and Parkkila S produced and characterized the primary antibodies; Statistical analysis was done by Mustonen H; Viikilä P drafted the first version of the manuscript; all authors were involved in the writing process, read, and approved the final manuscript.
Supported by the Sigrid Jusélius Foundation, the Academy of Finland, the Medical Research Funds of Tampere University Hospital and Helsinki University Hospital, and Jane and Aatos Erkko Foundation.
Institutional review board statement: The Ethical Committee of Helsinki University Hospital (Dnro 226/E6/2006) and National Supervisory Authority for Welfare and Health (Dnro 10041/06.01.03.01/2012) granted permission for the use of tissue samples.
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
Data sharing statement: Technical appendix, statistical code and dataset available from the corresponding author at viikila.pia.m@student.uta.fi. Participants consent was not obtained but the presented data are anonymized and there is no risk of identification.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Pia Viikilä, MD, School of Medicine, University of Tampere and Fimlab Ltd, Tampere University Hospital, Medisiinarinkatu 3, 33014 Tampere, Finland. viikila.pia.m@student.uta.fi
Telephone: +358-408-275235
Received: May 3, 2016
Peer-review started: May 4, 2016
First decision: May 27, 2016
Revised: June 9, 2016
Accepted: July 20, 2016
Article in press: July 21, 2016
Published online: September 28, 2016
AIM
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.
CONCLUSION
The present findings indicate that CA II and CA XII could be useful in predicting survival in CRC.
Core tip: Our aim was to investigate expression of four alpha-carbonic anhydrases (CAs) in colorectal carcinomas (CRC) and compare the results with patients’ survival. CRC samples were arranged as tissue microarrays and analyzed with antibodies against CA II, CA VII, CA IX, and CA XII. Enzyme expression levels were correlated to patients’ survival and clinicopathological parameters. CA II and CA XII staining intensities correlated with patients′ survival in that higher expression indicated poorer prognosis. The present findings indicate that CA II and CA XII could be useful in predicting survival in CRC.
