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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

Intensity of carbonic anhydrase IX (CA9) expression in esophageal adenocarcinoma with immunohistochemical staining. Samples were scored from 0 to 3: a, Negative (0, no stain or weak stain in <10 % cells). b, Weakly positive (1, weak stain in ≥ 10 % cells). c, Moderately positive (2, moderate stain in ≥ 10 % cells). d, strongly positive (3, strong stain in ≥ 10 % cells). CA9 expression was predominantly distributed in the tumor cell membrane
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Fig1: Intensity of carbonic anhydrase IX (CA9) expression in esophageal adenocarcinoma with immunohistochemical staining. Samples were scored from 0 to 3: a, Negative (0, no stain or weak stain in <10 % cells). b, Weakly positive (1, weak stain in ≥ 10 % cells). c, Moderately positive (2, moderate stain in ≥ 10 % cells). d, strongly positive (3, strong stain in ≥ 10 % cells). CA9 expression was predominantly distributed in the tumor cell membrane

Mentions: All sections were reviewed independently by Z.Z. and A.R.H. Both pathologists were blinded to all clinical and pathologic information. Discrepancies were reviewed by both Z.Z. and A.R.H., and a final consensus was reached. The percentage (0 %–100 %) of cells that stained positive was determined. The intensity of CA9, BMI1 and cyclin E staining was graded as follows: 0, no stain or weak stain in < 10 % cells; 1, weak stain in ≥ 10 % tumor cells; 2, moderate stain in ≥ 10 % cells; or 3, strong stain in ≥ 10 % cells (Fig. 1). CA9, BMI1, and cyclin E protein expression was considered high if 10 % or more of cells stained with an intensity score of 2 or 3 (Fig. 1). The intensity of MCM4, MCM7, and Ki67 immunostaining was graded as 0 (negative) or 1+ (positive). The percentage of cells with positive nuclear immunostaining, ranging from 0 to 100 % was recorded in the increments of 10.Fig. 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)

Intensity of carbonic anhydrase IX (CA9) expression in esophageal adenocarcinoma with immunohistochemical staining. Samples were scored from 0 to 3: a, Negative (0, no stain or weak stain in <10 % cells). b, Weakly positive (1, weak stain in ≥ 10 % cells). c, Moderately positive (2, moderate stain in ≥ 10 % cells). d, strongly positive (3, strong stain in ≥ 10 % cells). CA9 expression was predominantly distributed in the tumor cell membrane
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig1: Intensity of carbonic anhydrase IX (CA9) expression in esophageal adenocarcinoma with immunohistochemical staining. Samples were scored from 0 to 3: a, Negative (0, no stain or weak stain in <10 % cells). b, Weakly positive (1, weak stain in ≥ 10 % cells). c, Moderately positive (2, moderate stain in ≥ 10 % cells). d, strongly positive (3, strong stain in ≥ 10 % cells). CA9 expression was predominantly distributed in the tumor cell membrane
Mentions: All sections were reviewed independently by Z.Z. and A.R.H. Both pathologists were blinded to all clinical and pathologic information. Discrepancies were reviewed by both Z.Z. and A.R.H., and a final consensus was reached. The percentage (0 %–100 %) of cells that stained positive was determined. The intensity of CA9, BMI1 and cyclin E staining was graded as follows: 0, no stain or weak stain in < 10 % cells; 1, weak stain in ≥ 10 % tumor cells; 2, moderate stain in ≥ 10 % cells; or 3, strong stain in ≥ 10 % cells (Fig. 1). CA9, BMI1, and cyclin E protein expression was considered high if 10 % or more of cells stained with an intensity score of 2 or 3 (Fig. 1). The intensity of MCM4, MCM7, and Ki67 immunostaining was graded as 0 (negative) or 1+ (positive). The percentage of cells with positive nuclear immunostaining, ranging from 0 to 100 % was recorded in the increments of 10.Fig. 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