Cyclooxygenase-2 overexpression is associated with a poor outcome in resected ampullary cancer patients

Clin Cancer Res. 2005 May 15;11(10):3784-9. doi: 10.1158/1078-0432.CCR-04-2136.

Abstract

Purpose: To identify potential prognostic molecular factors in ampullary adenocarcinoma that could be of significant importance. To this end, we examined the possible prognostic significance of cyclooxygenase-2 (Cox-2) and Survivin expression and the apoptotic index in a cohort of uniformly treated patients with ampullary cancer treated with radical surgical excision.

Experimental design: The entry criteria were that the patients have a pathologic diagnosis of ampullary cancer which had been resected. Expression analysis for Cox-2 and Survivin was done by immunohistochemical staining. Apoptotic cells were identified by the terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method.

Results: Thirty-nine tumor specimens from resected ampullary adenocarcinoma patients were included. By univariate analysis, overall survival was affected by Cox-2 expression and TUNEL staining (respectively, P = 0.0003 and 0.03). Survivin expression did not influence the overall survival in our patient population (P = 0.123). Patients' clinicopathologic features (gender, age, and T and N factors) did not influence outcome. In multivariate Cox regression analysis, Cox-2 expression (relative risk, 4.330; P = 0.005) was the only variable that significantly affected overall survival.

Conclusions: The results of the present article provide, for the first time, evidence that Cox-2 expression, but not Survivin expression, may represent a significant prognostic factor after surgical resection in patients affected by cancer of the ampulla of Vater. Further studies are required to determine whether Cox-2 inhibitors may be useful for the therapy or prevention of ampullary carcinoma.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Ampulla of Vater / pathology*
  • Ampulla of Vater / surgery
  • Apoptosis
  • Common Bile Duct Neoplasms / genetics*
  • Common Bile Duct Neoplasms / pathology*
  • Common Bile Duct Neoplasms / surgery
  • Cyclooxygenase 2
  • Female
  • Gene Expression Profiling*
  • Humans
  • Immunohistochemistry
  • Inhibitor of Apoptosis Proteins
  • Male
  • Membrane Proteins
  • Microtubule-Associated Proteins / biosynthesis
  • Microtubule-Associated Proteins / genetics
  • Middle Aged
  • Neoplasm Proteins
  • Predictive Value of Tests
  • Prognosis
  • Prostaglandin-Endoperoxide Synthases / biosynthesis*
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • Survivin

Substances

  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Survivin
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases