Carbonic anhydrase enzymes Ⅱ, Ⅶ, Ⅸ and Ⅻ in colorectal carcinomas

• Published in: World journal of gastroenterology : WJG Vol. 22; no. 36; pp. 8168 - 8177
• Main Authors: Viikilä, Pia, Kivelä, Antti J, Mustonen, Harri, Koskensalo, Selja, Waheed, Abdul, Sly, William S, Doisy, Edward A, Pastorek, Jaromir, Pastorekova, Silvia, Parkkila, Seppo, Haglund, Caj
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Inc 28.09.2016
• Subjects: Aged; anhydrase;Colorectal; Antigens, Neoplasm - metabolism; Basic Study; Biomarker;Carbonic; Biomarkers, Tumor - metabolism; cancer;Immunohistochemistry;Prognosis;Survival; Carbonic Anhydrase II - metabolism; Carbonic Anhydrase IX - metabolism; Carbonic Anhydrases - metabolism; Colorectal Neoplasms - enzymology; Colorectal Neoplasms - mortality; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Male; Middle Aged; Prognosis; Proportional Hazards Models; Regression Analysis; Tissue Array Analysis; Treatment Outcome; Immunohistochemistry; Biomarker; Prognosis; Carbonic anhydrase; Survival; Colorectal cancer
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v22.i36.8168

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, KaplanMeier 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.