Expression of Cyclooxygenase-2 Is Associated with Carcinogenesis of the Lower Part of Thoracic Esophageal Squamous Cell Carcinoma and p53 Expression

Cyclooxygenase (COX) is a key enzyme in arachidonic acid metabolism. Two isoforms of this enzyme have been identified: constitutive COX-1 and inducible COX-2. Recently, expression of COX-2 has been found in several human carcinomas. COX-2 expression may contribute to the synthesis of prostanoids, which relate to carcinogenesis and tumor progression. We investigated the expression of COX-2 in 175 human esophageal squamous cell carcinoma tissues using immunohistochemistry and evaluated the relationship with clinicopathological findings. In addition, due to the known relevance of p53 to carcinogesis, we evaluated the expression of COX-2 and p53. Interestingly, cancer tissues with high COX-2 expression were found significantly more often in the middle and lower esophagus than in the cervical and upper esophagus (p = 0.0014). No significant differences were observed in other clinicopathological data such as age, sex, histopathological grading, lymphatic invasion, venous invasion, TNM clinical classification and patient prognosis. p53 expression was associated with the expression of COX-2 (p = 0.0122). Our findings suggest that COX-2 may play a role in the development of squamous cell carcinoma in the lower part of the thoracic esophagus.

[1]  T. Hattori,et al.  [Reflux of duodenal or gastroduodenal contents induces esophageal carcinoma in rats]. , 2004, Nihon rinsho. Japanese journal of clinical medicine.

[2]  M. Monden,et al.  Overexpression of cyclooxygenase-2 in carcinoma of the pancreas. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[3]  N. Altorki,et al.  Inhibition of Cyclooxygenase-2 Gene Expression by p53* , 1999, The Journal of Biological Chemistry.

[4]  M. Taketo,et al.  Size- and invasion-dependent increase in cyclooxygenase 2 levels in human colorectal carcinomas. , 1998, Cancer research.

[5]  Y. Yatabe,et al.  Increased expression of cyclooxygenase 2 occurs frequently in human lung cancers, specifically in adenocarcinomas. , 1998, Cancer research.

[6]  R. DuBois,et al.  Cyclooxygenase Regulates Angiogenesis Induced by Colon Cancer Cells , 1998, Cell.

[7]  S. Meltzer,et al.  Advances in Brief Increased Expression of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 in Barrett ' s Esophagus and Associated Adenocarcinomas 1 , 2006 .

[8]  R. DuBois,et al.  Cyclooxygenase Regulates Angiogenesis Induced by Colon Cancer Cells , 1998, Cell.

[9]  A. Tiburcio,et al.  Epithelial cell hyperproliferation after biliopancreatic reflux into the esophagus of rats. , 1998, The Annals of thoracic surgery.

[10]  Fan Zhang,et al.  Dihydroxy Bile Acids Activate the Transcription of Cyclooxygenase-2* , 1998, The Journal of Biological Chemistry.

[11]  A. Morrison,et al.  Overexpression of protein kinase C-zeta isoform increases cyclooxygenase-2 and inducible nitric oxide synthase. , 1997, The American journal of physiology.

[12]  A. Ristimäki,et al.  Expression of cyclooxygenase-2 in human gastric carcinoma. , 1997, Cancer research.

[13]  Bruno C. Hancock,et al.  Suppression of Intestinal Polyposis in Apc Δ716 Knockout Mice by Inhibition of Cyclooxygenase 2 (COX-2) , 1996, Cell.

[14]  T. Hattori,et al.  Reflux of duodenal or gastro‐duodenal contents induces esophageal carcinoma in rats , 1996, International journal of cancer.

[15]  John Calvin Reed,et al.  Immunohistochemical analysis of bcl-2, bax, bcl-X, and mcl-1 expression in prostate cancers. , 1996, The American journal of pathology.

[16]  R. DuBois,et al.  Increased cyclooxygenase-2 levels in carcinogen-induced rat colonic tumors. , 1996, Gastroenterology.

[17]  H. Handa,et al.  Induction of the transcription factor AP-1 in cultured human colon adenocarcinoma cells following exposure to bile acids. , 1996, Carcinogenesis.

[18]  R. DuBois,et al.  Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2 , 1995, Cell.

[19]  M. Kondo,et al.  Expression of cyclooxygenase-1 and -2 in human colorectal cancer. , 1995, Cancer research.

[20]  S Jothy,et al.  Expression of prostaglandin G/H synthase-1 and -2 protein in human colon cancer. , 1995, Cancer research.

[21]  P. Cagle,et al.  p53 immunostaining in the differentiation of reactive processes from malignancy in pleural biopsy specimens. , 1994, Human pathology.

[22]  S. Piantadosi,et al.  Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. , 1993, The New England journal of medicine.

[23]  M. Thun,et al.  Aspirin use and risk of fatal cancer. , 1993, Cancer research.

[24]  R. Metcalf,et al.  p53 mutation and protein accumulation during multistage human esophageal carcinogenesis. , 1992, Cancer research.

[25]  L. Marnett Aspirin and the potential role of prostaglandins in colon cancer. , 1992, Cancer research.

[26]  M. Castagna,et al.  Bile acids, non‐phorbol‐ester‐type tumor promoters, stimulate the phosphorylation of protein kinase C substrates in human platelets and colon cell line HT29 , 1992, International journal of cancer.

[27]  Ribet Me,et al.  Reflux esophagitis and carcinoma. , 1992 .

[28]  C. Rubio,et al.  Barrett's mucosa in conjunction with squamous carcinoma of the esophagus , 1991, Cancer.

[29]  M. Toubin,et al.  Gas chromatographic/mass spectrometric quantitative analysis of eicosanoids in human oesophageal mucosa. , 1988, Biomedical & environmental mass spectrometry.

[30]  J. Guillem,et al.  Studies on protein kinase C and colon carcinogenesis. , 1987, Archives of surgery.

[31]  G. Kelloff,et al.  Dose-related inhibition of colon carcinogenesis by dietary piroxicam, a nonsteroidal antiinflammatory drug, during different stages of rat colon tumor development. , 1987, Cancer research.

[32]  M. Imamura,et al.  Retrosternal Esophagogastrostomy with the EEA Stapler after Subtotal Resection of the Esophagus: Application and Results , 1987 .

[33]  E. Munck‐Wikland,et al.  Esophagitis and cancer of the esophagus , 1985, Cancer.

[34]  J. Ceuppens,et al.  Regulation of the immune response by prostaglandins , 1983, Journal of Clinical Immunology.

[35]  W. Waddell,et al.  Sulindac for polyposis of the colon , 1983, Journal of surgical oncology.

[36]  L. Marnett,et al.  Prostaglandins and cancer: a review of tumor initiation through tumor metastasis. , 1981, Prostaglandins.

[37]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[38]  K. Schrör,et al.  Cyclooxygenase-2 expression in human esophageal carcinoma. , 1999, Cancer research.

[39]  E. Mensier,et al.  Reflux esophagitis and carcinoma. , 1992, Surgery, gynecology & obstetrics.