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Carbonic Anhydrase XII as an Independent Prognostic Factor in Advanced Esophageal Squamous Cell Carcinoma.

Ochi F, Shiozaki A, Ichikawa D, Fujiwara H, Nakashima S, Takemoto K, Kosuga T, Konishi H, Komatsu S, Okamoto K, Kishimoto M, Marunaka Y, Otsuji E - J Cancer (2015)

Bottom Line: Although the expression of CA XII was related to the pT category, it had no prognostic impact.We then examined the expression of CA XII according to the pT category.In pT2-3 ESCC, the 3-year survival rate of patients with the high grade expression of CA XII (29.1 %) was significantly lower than that of patients with the low grade expression of CA XII (70.3 %).

View Article: PubMed Central - PubMed

Affiliation: 1. Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.

ABSTRACT

Background: Although recent studies described important roles for carbonic anhydrase (CA) XII in epithelial carcinogenesis and tumor behavior, a consensus has not yet been reached regarding its clinicopathological significance in esophageal squamous cell carcinoma (ESCC). In the present study, we investigated its prognostic significance in ESCC.

Materials and methods: An immunohistochemical analysis was performed on 70 primary tumor samples obtained from ESCC patients who underwent esophagectomy, and the relationships between the expression of CA XII and various clinicopathological features or prognosis were analyzed.

Results: Immunohistochemical staining showed that CA XII was primarily found in the cell membranes of carcinoma cells. Although the expression of CA XII was related to the pT category, it had no prognostic impact. We then examined the expression of CA XII according to the pT category. In pT2-3 ESCC, the 3-year survival rate of patients with the high grade expression of CA XII (29.1 %) was significantly lower than that of patients with the low grade expression of CA XII (70.3 %). Furthermore, a multivariate analysis demonstrated that the expression of CA XII was one of the most important independent prognostic factors following radical esophagectomy in pT2-3 ESCC.

Conclusion: These results suggest that the expression of CA XII may be a valuable prognostic factor for patients with advanced ESCC. The results of the present study provide an insight into the role of CA XII as a biomarker in ESCC.

No MeSH data available.


Related in: MedlinePlus

A: Immunohistochemical staining of human esophageal precancerous tissue with the CA XII antibody. CA XII protein expression was found in esophageal dysplasia. Magnification: ×100. B: The comparison between CA XII and HIF-1α protein expressions in human ESCC tissues. Immunohistochemical staining patterns of CA XII (high) and HIF-1α (low) were similar. Magnification: ×40 (left), ×200 (right).
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Figure 2: A: Immunohistochemical staining of human esophageal precancerous tissue with the CA XII antibody. CA XII protein expression was found in esophageal dysplasia. Magnification: ×100. B: The comparison between CA XII and HIF-1α protein expressions in human ESCC tissues. Immunohistochemical staining patterns of CA XII (high) and HIF-1α (low) were similar. Magnification: ×40 (left), ×200 (right).

Mentions: An immunohistochemical investigation with the CA XII antibody revealed the expression of CA XII in the parabasal cell layer of normal esophageal mucosa (Fig. 1A). We examined the expression of CA XII in 70 primary tumor samples of human ESCC based on their immunohistochemical reactivities. The CA XII protein was mostly expressed in the cell membranes of carcinoma cells (Fig. 1B). The CA XII score varied widely between the tumors. The minimum CA XII score was 0, while the maximum was 2.5 (median= 0.40; mean±standard deviation (SD) = 0.65±0.64). Regarding the expression of CA XII in tumors, we divided ESCC patients into 2 groups by referring to the median and mean staining scores; a low grade CA XII expression group with staining scores<0.5, n=35, and a high grade CA XII expression group with staining scores≥0.5, n=35. Figure 1CD shows the representative histopathological findings of low or high CA XII expression samples. Relationships between the expression of CA XII and various clinicopathological parameters were analyzed (Table I). A correlation was observed between the expression of CA XII and the pT category (Table I). We then analyzed CA XII expression according to the pT category. In patients with pT1 ESCC (n=33), the minimum CA XII score was 0, while the maximum was 2.5 (median= 0.70; mean±SD= 0.80±0.66), and correlations were found between the expression of CA XII and venous invasion (Table II). On the other hand, the minimum CA XII score in patients with pT2-3 ESCC (n=37) was 0, while the maximum was 2.4 (median= 0.20; mean±SD= 0.51±0.60), and no correlation was found between the expression of CA XII and any other clinicopathological parameter (Table III). Interestingly, the expression of CA XII was found in precancerous tissue such as severe dysplasia (Fig. 2A). These results suggested that CA XII may be induced in esophageal epithelial cells in the early stage of carcinogenesis.


Carbonic Anhydrase XII as an Independent Prognostic Factor in Advanced Esophageal Squamous Cell Carcinoma.

Ochi F, Shiozaki A, Ichikawa D, Fujiwara H, Nakashima S, Takemoto K, Kosuga T, Konishi H, Komatsu S, Okamoto K, Kishimoto M, Marunaka Y, Otsuji E - J Cancer (2015)

A: Immunohistochemical staining of human esophageal precancerous tissue with the CA XII antibody. CA XII protein expression was found in esophageal dysplasia. Magnification: ×100. B: The comparison between CA XII and HIF-1α protein expressions in human ESCC tissues. Immunohistochemical staining patterns of CA XII (high) and HIF-1α (low) were similar. Magnification: ×40 (left), ×200 (right).
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4543752&req=5

Figure 2: A: Immunohistochemical staining of human esophageal precancerous tissue with the CA XII antibody. CA XII protein expression was found in esophageal dysplasia. Magnification: ×100. B: The comparison between CA XII and HIF-1α protein expressions in human ESCC tissues. Immunohistochemical staining patterns of CA XII (high) and HIF-1α (low) were similar. Magnification: ×40 (left), ×200 (right).
Mentions: An immunohistochemical investigation with the CA XII antibody revealed the expression of CA XII in the parabasal cell layer of normal esophageal mucosa (Fig. 1A). We examined the expression of CA XII in 70 primary tumor samples of human ESCC based on their immunohistochemical reactivities. The CA XII protein was mostly expressed in the cell membranes of carcinoma cells (Fig. 1B). The CA XII score varied widely between the tumors. The minimum CA XII score was 0, while the maximum was 2.5 (median= 0.40; mean±standard deviation (SD) = 0.65±0.64). Regarding the expression of CA XII in tumors, we divided ESCC patients into 2 groups by referring to the median and mean staining scores; a low grade CA XII expression group with staining scores<0.5, n=35, and a high grade CA XII expression group with staining scores≥0.5, n=35. Figure 1CD shows the representative histopathological findings of low or high CA XII expression samples. Relationships between the expression of CA XII and various clinicopathological parameters were analyzed (Table I). A correlation was observed between the expression of CA XII and the pT category (Table I). We then analyzed CA XII expression according to the pT category. In patients with pT1 ESCC (n=33), the minimum CA XII score was 0, while the maximum was 2.5 (median= 0.70; mean±SD= 0.80±0.66), and correlations were found between the expression of CA XII and venous invasion (Table II). On the other hand, the minimum CA XII score in patients with pT2-3 ESCC (n=37) was 0, while the maximum was 2.4 (median= 0.20; mean±SD= 0.51±0.60), and no correlation was found between the expression of CA XII and any other clinicopathological parameter (Table III). Interestingly, the expression of CA XII was found in precancerous tissue such as severe dysplasia (Fig. 2A). These results suggested that CA XII may be induced in esophageal epithelial cells in the early stage of carcinogenesis.

Bottom Line: Although the expression of CA XII was related to the pT category, it had no prognostic impact.We then examined the expression of CA XII according to the pT category.In pT2-3 ESCC, the 3-year survival rate of patients with the high grade expression of CA XII (29.1 %) was significantly lower than that of patients with the low grade expression of CA XII (70.3 %).

View Article: PubMed Central - PubMed

Affiliation: 1. Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.

ABSTRACT

Background: Although recent studies described important roles for carbonic anhydrase (CA) XII in epithelial carcinogenesis and tumor behavior, a consensus has not yet been reached regarding its clinicopathological significance in esophageal squamous cell carcinoma (ESCC). In the present study, we investigated its prognostic significance in ESCC.

Materials and methods: An immunohistochemical analysis was performed on 70 primary tumor samples obtained from ESCC patients who underwent esophagectomy, and the relationships between the expression of CA XII and various clinicopathological features or prognosis were analyzed.

Results: Immunohistochemical staining showed that CA XII was primarily found in the cell membranes of carcinoma cells. Although the expression of CA XII was related to the pT category, it had no prognostic impact. We then examined the expression of CA XII according to the pT category. In pT2-3 ESCC, the 3-year survival rate of patients with the high grade expression of CA XII (29.1 %) was significantly lower than that of patients with the low grade expression of CA XII (70.3 %). Furthermore, a multivariate analysis demonstrated that the expression of CA XII was one of the most important independent prognostic factors following radical esophagectomy in pT2-3 ESCC.

Conclusion: These results suggest that the expression of CA XII may be a valuable prognostic factor for patients with advanced ESCC. The results of the present study provide an insight into the role of CA XII as a biomarker in ESCC.

No MeSH data available.


Related in: MedlinePlus