Cyclooxygenase-2 expression in squamous dysplasia and squamous cell carcinoma of the esophagus

Cancer Lett. 2003 Aug 20;198(2):193-201. doi: 10.1016/s0304-3835(03)00340-9.


Cyclooxygenase-2 (cox-2) overexpression has been observed in several types of human cancers and has been implicated in carcinogenesis. To elucidate the role of cox-2 in esophageal carcinogenesis, we evaluated the expression of cox-2 in normal squamous epithelium squamous epithelial dysplasia (n=47), and squamous cell carcinoma of the esophagus (n=86) by immunohistochemistry, reverse transcription-PCR assay, and western blotting. A significant overexpression of cox-2 was observed in esophageal squamous dysplasia and squamous cell carcinoma compared with normal squamous epithelium. The immunoreactive score of cox-2 expression, an index determined by intensity and positivity of cox-2 staining, was 0.71 +/- 0.46 (mean +/- SD) in normal squamous esophagus, 2.19 +/- 1.79 in squamous epithelial dysplasia, and 2.67 +/- 1.77 in squamous cell carcinoma. The results of immunohistochemistry were confirmed by a reverse transcription-PCR assay and western blotting analysis. Cox-2 expression level was correlated with proliferation activity assessed by proliferating cell nuclear antigen (PCNA) index and MIB-1 index in dysplastic lesion (r=0.55, P<0.01 with PCNA and r=0.72, P<0.01 with MIB-1) and carcinoma (r=0.56, P<0.01 with PCNA and r=0.72, P<0.01 with MIB-1). Elevated cox-2 expression was associated with high p53 expression (p<0.001) but not with clinicopathological features including age, sex, tumor size, histological grade, lymph node metastasis, and TNM stage. The results indicated that cox-2 may be involved in an early stage of squamous carcinogenesis of the esophagus, and that cox-2 overexpression was related to cell proliferation in esophageal squamous dysplasia and squamous cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Blotting, Western
  • Carcinoma, Squamous Cell / enzymology*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / surgery
  • Cell Division
  • Cyclooxygenase 2
  • Esophageal Neoplasms / enzymology*
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / surgery
  • Esophagus / enzymology
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Isoenzymes / genetics*
  • Ki-67 Antigen / analysis
  • Membrane Proteins
  • Neoplasm Staging
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • RNA, Messenger / genetics
  • Reference Values
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic


  • Isoenzymes
  • Ki-67 Antigen
  • Membrane Proteins
  • RNA, Messenger
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases