Increased expression of VEGF, COX-2, and Ki-67 in Barrett's esophagus: does the length matter?

Dig Dis Sci. 2012 May;57(5):1190-6. doi: 10.1007/s10620-011-1990-6. Epub 2011 Dec 7.

Abstract

Background: Barrett's esophagus (BE) is a major complication of gastroesophageal reflux disease due to its neoplastic potential. The length of the metaplastic epithelium has been associated with cancer risk. Angiogenesis, inflammation, and increased cell proliferation are early events in the malignant sequence. Vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2) and Ki-67 are indirect markers of these complex mechanisms.

Aims: To examine the expression of VEGF, COX-2 and Ki-67 in BE and investigate whether there is an association to Barrett's length.

Methods: Immunohistochemistry for VEGF, COX-2, and Ki-67 was performed in well-characterized Barrett's samples, evaluated using a qualitative scale and compared between long (LSBE) and short (SSBE) segments.

Results: The study population consisted of 98 patients (78 men). LSBE and SSBE was diagnosed in 33 (33.7%) and 65 (66.3%) cases, respectively. VEGF was expressed in vascular endothelium of all Barrett's specimens. COX-2 and Ki-67 expression in metaplastic epithelia was strong in 81.6 and 61.2% of the samples, respectively. Ki-67 expression was significantly stronger in LSBE (p = 0.035), whereas VEGF expression was significantly increased in SSBE (p = 0.031). COX-2 expression was not associated with Barrett's length.

Conclusions: VEGF, COX-2, and Ki-67 were overexpressed in the majority of Barrett's samples. The length was inversely associated with VEGF expression and directly associated with Ki-67 expression.

MeSH terms

  • Adult
  • Aged
  • Barrett Esophagus* / complications
  • Barrett Esophagus* / genetics
  • Barrett Esophagus* / metabolism
  • Barrett Esophagus* / pathology
  • Biomarkers
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cyclooxygenase 2 / genetics*
  • Cyclooxygenase 2 / metabolism
  • Early Detection of Cancer
  • Esophageal Neoplasms* / etiology
  • Esophageal Neoplasms* / genetics
  • Esophageal Neoplasms* / metabolism
  • Esophageal Neoplasms* / pathology
  • Esophagus / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Inflammation / genetics
  • Inflammation / metabolism
  • Ki-67 Antigen / genetics*
  • Ki-67 Antigen / metabolism
  • Male
  • Middle Aged
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Risk Factors
  • Vascular Endothelial Growth Factor A / genetics*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Biomarkers
  • Ki-67 Antigen
  • Vascular Endothelial Growth Factor A
  • Cyclooxygenase 2