Abstract
BackgroundCarbonic 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.MethodsIn 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 discussionCA9 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.ConclusionsHigh 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.
Highlights
Carbonic anhydrase IX (CA9) is a transmembrane glycoprotein related to hypoxia
High Carbonic anhydrase 9 (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
High CA9 expression in esophageal adenocarcinoma and precancerous lesions Immunostaining results showed that CA9 was predominantly expressed in the cell membrane and rarely in the cytoplasm (Fig. 1)
Summary
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. CA9 expression has been associated with tumor acid–base homeostasis under conditions of hypoxia, cancer progression, metastasis, and impaired response to traditional therapy [4, 5, 9] and is found in many types of cancer, including those of the kidney, bile duct, stomach, esophagus, lung, breast, cervix, ovaries, bladder, brain, head and neck, and oral cavity [4,5,6,7,8,9,10,11,12,13,14,15]. The percentages of expression of CA9 in these studies vary, and CA9 expression in precancerous lesions has not been well studied
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