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

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Immunohistochemical stainings of carbonic anhydrases II, VII, IX and XII. CA II (A, B, C), CA VII (D, E, F), CA IX (G, H, I), and CA XII (J, K, L) are shown in specimens of normal pancreas (A, D, G, J), colon (B, E, H, K) and colorectal carcinoma (C, F, I, L). The normal pancreas and colon sections were used for control purposes. CA II was located to the pancreatic ducts and centroacinar cells. In normal colon the staining is strongest in the enterocytes of deep crypts. In colorectal cancer, CA II is strongly expressed in cancer cells. CA VII stains stromal tissue in all specimens, while the cancer cells show only minimal or no staining. CA IX antibody weakly stains ductal and some acinar cells of pancreatic tissue and also basolateral cell membranes in basal parts of colonic crypts. In colorectal cancer, CA IX is strongly expressed in malignant cells, whereas the necrotic part is negative. CA XII antibody stains basolateral membranes of pancreatic acinar cells and colonic enterocytes, and malignant cells of colon carcinoma. Original magnifications × 400, Bars 50 μm.
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Figure 1: Immunohistochemical stainings of carbonic anhydrases II, VII, IX and XII. CA II (A, B, C), CA VII (D, E, F), CA IX (G, H, I), and CA XII (J, K, L) are shown in specimens of normal pancreas (A, D, G, J), colon (B, E, H, K) and colorectal carcinoma (C, F, I, L). The normal pancreas and colon sections were used for control purposes. CA II was located to the pancreatic ducts and centroacinar cells. In normal colon the staining is strongest in the enterocytes of deep crypts. In colorectal cancer, CA II is strongly expressed in cancer cells. CA VII stains stromal tissue in all specimens, while the cancer cells show only minimal or no staining. CA IX antibody weakly stains ductal and some acinar cells of pancreatic tissue and also basolateral cell membranes in basal parts of colonic crypts. In colorectal cancer, CA IX is strongly expressed in malignant cells, whereas the necrotic part is negative. CA XII antibody stains basolateral membranes of pancreatic acinar cells and colonic enterocytes, and malignant cells of colon carcinoma. Original magnifications × 400, Bars 50 μm.

Mentions: Four CA isozymes, CA II, VII, IX, and XII were selected for the immunohistochemical analysis of colorectal cancer and the summary of these results is presented in Table 2. Figure 1 presents representative images of positive immunostaining of each isozyme in CRC specimens. Normal colon and pancreas specimens are shown as positive controls. Figure 2 shows Kaplan-Meier plots for the staining intensity and extent of each isozyme. In Kaplan-Meier analysis, there was a significant decrease in survival as the intensity of CA II increased. The mean survival time decreased from 17.7 years (95% CI, 14.8-20.6) to 12.3 years (95%CI: 10.5-14.2) when CA II intensity increased from 0 to 3. The extent of CA II staining showed a similar trend (P = 0.022). Correspondingly, the mean survival time decreased from 18.3 years (95%CI: 15.5-21.1) to 13.5 years (95%CI: 12.0-15.0).


Carbonic anhydrase enzymes II, VII, IX and XII in colorectal carcinomas
Immunohistochemical stainings of carbonic anhydrases II, VII, IX and XII. CA II (A, B, C), CA VII (D, E, F), CA IX (G, H, I), and CA XII (J, K, L) are shown in specimens of normal pancreas (A, D, G, J), colon (B, E, H, K) and colorectal carcinoma (C, F, I, L). The normal pancreas and colon sections were used for control purposes. CA II was located to the pancreatic ducts and centroacinar cells. In normal colon the staining is strongest in the enterocytes of deep crypts. In colorectal cancer, CA II is strongly expressed in cancer cells. CA VII stains stromal tissue in all specimens, while the cancer cells show only minimal or no staining. CA IX antibody weakly stains ductal and some acinar cells of pancreatic tissue and also basolateral cell membranes in basal parts of colonic crypts. In colorectal cancer, CA IX is strongly expressed in malignant cells, whereas the necrotic part is negative. CA XII antibody stains basolateral membranes of pancreatic acinar cells and colonic enterocytes, and malignant cells of colon carcinoma. Original magnifications × 400, Bars 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037085&req=5

Figure 1: Immunohistochemical stainings of carbonic anhydrases II, VII, IX and XII. CA II (A, B, C), CA VII (D, E, F), CA IX (G, H, I), and CA XII (J, K, L) are shown in specimens of normal pancreas (A, D, G, J), colon (B, E, H, K) and colorectal carcinoma (C, F, I, L). The normal pancreas and colon sections were used for control purposes. CA II was located to the pancreatic ducts and centroacinar cells. In normal colon the staining is strongest in the enterocytes of deep crypts. In colorectal cancer, CA II is strongly expressed in cancer cells. CA VII stains stromal tissue in all specimens, while the cancer cells show only minimal or no staining. CA IX antibody weakly stains ductal and some acinar cells of pancreatic tissue and also basolateral cell membranes in basal parts of colonic crypts. In colorectal cancer, CA IX is strongly expressed in malignant cells, whereas the necrotic part is negative. CA XII antibody stains basolateral membranes of pancreatic acinar cells and colonic enterocytes, and malignant cells of colon carcinoma. Original magnifications × 400, Bars 50 μm.
Mentions: Four CA isozymes, CA II, VII, IX, and XII were selected for the immunohistochemical analysis of colorectal cancer and the summary of these results is presented in Table 2. Figure 1 presents representative images of positive immunostaining of each isozyme in CRC specimens. Normal colon and pancreas specimens are shown as positive controls. Figure 2 shows Kaplan-Meier plots for the staining intensity and extent of each isozyme. In Kaplan-Meier analysis, there was a significant decrease in survival as the intensity of CA II increased. The mean survival time decreased from 17.7 years (95% CI, 14.8-20.6) to 12.3 years (95%CI: 10.5-14.2) when CA II intensity increased from 0 to 3. The extent of CA II staining showed a similar trend (P = 0.022). Correspondingly, the mean survival time decreased from 18.3 years (95%CI: 15.5-21.1) to 13.5 years (95%CI: 12.0-15.0).

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus