Clinical and prognosis relevance of COX-2 expression in Tunisian patients with primary gastric adenocarcinoma

Cancer Biomark. 2016 Jun 7;17(1):67-73. doi: 10.3233/CBM-160618.

Abstract

Background: Inflammation and hormonal signalling induce the cyclooxygenase-2 (COX-2) expression in various human cancers including Gastric Cancer (GC). GC remains among the human malignancies diagnosticated at advanced tumor stage and thus having a poor prognosis. COX-2 is a key protein in cancer progression which is involved in proliferation, invasion, and metastasis of tumor cells.

Objective: The aim of this study was to investigate the expression of COX-2 and its association with clinico-patholocigal parameters and survival in Tunisian GC patients and to correlate COX-2 expression with others cancer-related proteins.

Methods: The immunohistochemistry was used to study the expression of COX-2 on 93 patients with gastric adenocarcinoma.

Results: Our results show that COX-2 immunostaining is negative to weak in 51.6%, moderate in 33.3%, and intense in 15.1% of tumor tissues. The expression of COX-2 associated significantly with tumor differentiation (p = 0.003), and histological type (p = 0.039). Furthermore, lack of COX-2 expression is significantly associated with 1-year (p= 0.005), 2-years (p= 0.000), and 5-years (p= 0.042) relapse free survival. In addition, Cox regression model, revealed that metastasis (p= 0.014), tumor site (p= 0.013), histotype (p = 0.02), and COX-2 expression (p = 0.003) are independent factors for prognosis. Regarding the relationship between COX-2 and cancer related proteins, we found that COX-2 expression is positively associated with APC (p = 0.006), and P53 (p = 0.026), supporting a cross link between these proteins in gastric carcinogenesis.

Conclusion: Our findings emphasize the importance of COX-2 as a potential marker of tumor progression and prognosis in GC, and that the inhibition of COX-2 activity may have a therapeutic benefit in GC.

Keywords: COX-2; gastric carcinoma; immunohistochemistry; prognosis.

MeSH terms

  • Adenocarcinoma / diagnosis*
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / mortality
  • Adult
  • Aged
  • Cyclooxygenase 2 / genetics*
  • Cyclooxygenase 2 / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Neoplasms / diagnosis*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / mortality
  • Tunisia

Substances

  • Cyclooxygenase 2