title: High expression of carbonic anhydrase IX is significantly associated with glandular lesions in gastroesophageal junction and with tumorigenesis markers BMI1, MCM4 and MCM7.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Box 626, Rochester, NY, 14642, USA. AHuber@pathgroup.com.
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Huber
authors.affiliation: Department of Pathology, MD Anderson Cancer Institute, Houston, TX, USA. dtan@mail.mdanderson.org.
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Tan
authors.affiliation: Biochemistry, Rush University Medical Center, Chicago, IL, USA. jun_sun@rush.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Pediatrics, University of Rochester, Rochester, NY, USA. David_dean@urmc.rochester.edu.
authors.forename: David
authors.initials: D
authors.lastname: Dean
authors.affiliation: Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY, USA. Tongtong_Wu@URMC.Rochester.edu.
authors.forename: Tongtong
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Box 626, Rochester, NY, 14642, USA. David_Zhou@urmc.rochester.edu.
authors.forename: Zhongren
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000378:metabolism*; D063646:Carcinogenesis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D019927:Cyclin E / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D004943:Esophagogastric Junction / Q000473:pathology*; D005260:Female; D005764:Gastroesophageal Reflux / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D064148:Minichromosome Maintenance Complex Component 4 / Q000378:metabolism; D064168:Minichromosome Maintenance Complex Component 7 / Q000378:metabolism; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology; D011379:Prognosis
chemical_list: D000951:Antigens, Neoplasm; C069077:BMI1 protein, human; D014408:Biomarkers, Tumor; D019927:Cyclin E; D019394:Ki-67 Antigen; D063150:Polycomb Repressive Complex 1; C099243:MCM4 protein, human; C101624:MCM7 protein, human; D064148:Minichromosome Maintenance Complex Component 4; D064168:Minichromosome Maintenance Complex Component 7; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases