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High expression of carbonic anhydrase IX is significantly associated with glandular lesions in gastroesophageal junction and with tumorigenesis markers BMI1, MCM4 and MCM7.

Huber AR, Tan D, Sun J, Dean D, Wu T, Zhou Z - BMC Gastroenterol (2015)

Bottom Line: Survival duration of esophageal adenocarcinoma did not significantly differ between patients with high CA9 expression and those with low expression.High CA9 expression is significantly associated with BMI1, cyclin E, Ki67, MCM4 and MCM7 expression.High CA9 expression may be related to the acidic environment caused by gastroesophageal reflux disease in the gastroesophageal junction and associated with tumorigenesis through BMI1, MCM4 and MCM7.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Box 626, Rochester, NY, 14642, USA. AHuber@pathgroup.com.

ABSTRACT

Background: Carbonic anhydrase IX (CA9) is a transmembrane glycoprotein related to hypoxia. Increased CA9 expression has been associated with decreased survival and cancer progression and has been targeted as a potential therapy for several cancers, including esophageal cancer. The reported percentages of expression of CA9 in esophageal adenocarcinoma vary, and CA9 expression in precancerous esophageal lesions has not been well studied.

Methods: In this study, we investigated CA9 expression in esophageal cancers and in precancerous lesions and explored the association of CA9 expression with prognostic factors and with stem cell and tumorigenesis-related markers including BMI1, cyclin E, ki67, MCM4 and MCM7 expression. Previously constructed tissue microarrays consisting of samples of 7 tissue types (columnar cell metaplasia, Barrett esophagus, low- and high-grade dysplasia, esophageal adenocarcinoma, squamous epithelium, and squamous cell carcinoma) were used for the immunostaining of CA9, BMI1, cyclin E, Ki67, MCM4 and MCM7.

Results and discussion: CA9 high expression occurred more frequently in glandular mucosa with or without dysplasia than in squamous epithelium or squamous cell carcinoma. Survival duration of esophageal adenocarcinoma did not significantly differ between patients with high CA9 expression and those with low expression. High CA9 expression is significantly associated with BMI1, cyclin E, Ki67, MCM4 and MCM7 expression.

Conclusions: High CA9 expression may be related to the acidic environment caused by gastroesophageal reflux disease in the gastroesophageal junction and associated with tumorigenesis through BMI1, MCM4 and MCM7.

No MeSH data available.


Related in: MedlinePlus

Squamous epithelium and esophageal squamous cell carcinoma samples showed no high intensity of carbonic anhydrase IX (CA9) expression. a. Squamous epithelium with H&E stain; b. No high CA9 expression in squamous epithelium; c. Squamous cell carcinoma with H&E stain; d. No high CA9 expression in sqaumous cell carcinoma
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Fig2: Squamous epithelium and esophageal squamous cell carcinoma samples showed no high intensity of carbonic anhydrase IX (CA9) expression. a. Squamous epithelium with H&E stain; b. No high CA9 expression in squamous epithelium; c. Squamous cell carcinoma with H&E stain; d. No high CA9 expression in sqaumous cell carcinoma

Mentions: Immunostaining results showed that CA9 was predominantly expressed in the cell membrane and rarely in the cytoplasm (Fig. 1). Of the tissue microarray cases, 90 % (101/112) esophageal adenocarcinoma, 94 % (16/17) high-grade dysplasia, 85 % (17/20) low-grade dysplasia, 74 % (20/27) Barrett esophagus, 83 % (48/58) columnar cell metaplasia, 9 % (2/23) squamous cell carcinoma, and 0 % (0/62) squamous epithelium had high CA9 expression (Table 1, Fig. 1, 2 and 3). The rate of high CA9 expression in patients with squamous cell carcinoma or squamous epithelium was significantly lower than that in patients with esophageal adenocarcinoma, high-grade dysplasia, low-grade dysplasia, Barrett esophagus, or columnar cell metaplasia (Table 2). High CA9 expression occurred predominantly in columnar cell lesions but was rare or absent in squamous cell carcinoma and squamous epithelium (Fig. 2).Table 1


High expression of carbonic anhydrase IX is significantly associated with glandular lesions in gastroesophageal junction and with tumorigenesis markers BMI1, MCM4 and MCM7.

Huber AR, Tan D, Sun J, Dean D, Wu T, Zhou Z - BMC Gastroenterol (2015)

Squamous epithelium and esophageal squamous cell carcinoma samples showed no high intensity of carbonic anhydrase IX (CA9) expression. a. Squamous epithelium with H&E stain; b. No high CA9 expression in squamous epithelium; c. Squamous cell carcinoma with H&E stain; d. No high CA9 expression in sqaumous cell carcinoma
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
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getmorefigures.php?uid=PMC4495619&req=5

Fig2: Squamous epithelium and esophageal squamous cell carcinoma samples showed no high intensity of carbonic anhydrase IX (CA9) expression. a. Squamous epithelium with H&E stain; b. No high CA9 expression in squamous epithelium; c. Squamous cell carcinoma with H&E stain; d. No high CA9 expression in sqaumous cell carcinoma
Mentions: Immunostaining results showed that CA9 was predominantly expressed in the cell membrane and rarely in the cytoplasm (Fig. 1). Of the tissue microarray cases, 90 % (101/112) esophageal adenocarcinoma, 94 % (16/17) high-grade dysplasia, 85 % (17/20) low-grade dysplasia, 74 % (20/27) Barrett esophagus, 83 % (48/58) columnar cell metaplasia, 9 % (2/23) squamous cell carcinoma, and 0 % (0/62) squamous epithelium had high CA9 expression (Table 1, Fig. 1, 2 and 3). The rate of high CA9 expression in patients with squamous cell carcinoma or squamous epithelium was significantly lower than that in patients with esophageal adenocarcinoma, high-grade dysplasia, low-grade dysplasia, Barrett esophagus, or columnar cell metaplasia (Table 2). High CA9 expression occurred predominantly in columnar cell lesions but was rare or absent in squamous cell carcinoma and squamous epithelium (Fig. 2).Table 1

Bottom Line: Survival duration of esophageal adenocarcinoma did not significantly differ between patients with high CA9 expression and those with low expression.High CA9 expression is significantly associated with BMI1, cyclin E, Ki67, MCM4 and MCM7 expression.High CA9 expression may be related to the acidic environment caused by gastroesophageal reflux disease in the gastroesophageal junction and associated with tumorigenesis through BMI1, MCM4 and MCM7.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Box 626, Rochester, NY, 14642, USA. AHuber@pathgroup.com.

ABSTRACT

Background: Carbonic anhydrase IX (CA9) is a transmembrane glycoprotein related to hypoxia. Increased CA9 expression has been associated with decreased survival and cancer progression and has been targeted as a potential therapy for several cancers, including esophageal cancer. The reported percentages of expression of CA9 in esophageal adenocarcinoma vary, and CA9 expression in precancerous esophageal lesions has not been well studied.

Methods: In this study, we investigated CA9 expression in esophageal cancers and in precancerous lesions and explored the association of CA9 expression with prognostic factors and with stem cell and tumorigenesis-related markers including BMI1, cyclin E, ki67, MCM4 and MCM7 expression. Previously constructed tissue microarrays consisting of samples of 7 tissue types (columnar cell metaplasia, Barrett esophagus, low- and high-grade dysplasia, esophageal adenocarcinoma, squamous epithelium, and squamous cell carcinoma) were used for the immunostaining of CA9, BMI1, cyclin E, Ki67, MCM4 and MCM7.

Results and discussion: CA9 high expression occurred more frequently in glandular mucosa with or without dysplasia than in squamous epithelium or squamous cell carcinoma. Survival duration of esophageal adenocarcinoma did not significantly differ between patients with high CA9 expression and those with low expression. High CA9 expression is significantly associated with BMI1, cyclin E, Ki67, MCM4 and MCM7 expression.

Conclusions: High CA9 expression may be related to the acidic environment caused by gastroesophageal reflux disease in the gastroesophageal junction and associated with tumorigenesis through BMI1, MCM4 and MCM7.

No MeSH data available.


Related in: MedlinePlus