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


CONCLUSIONS
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.
Laboratory of Molecular Biotechnology of Eukaryotic, Center of Biotechnology of Sfax, University of Sfax, Sfax, Tunisia.
Dorra
D
Ben Ayed-Guerfali
Departement of Anatomopathology, CHU Habib Bourguiba Sfax, Sfax, Tunisia.
Slim
S
Charfi
Departement of Anatomopathology, CHU Habib Bourguiba Sfax, Sfax, Tunisia.
Abdelmajid
A
Khabir
Departement of Anatomopathology, CHU Habib Bourguiba Sfax, Sfax, Tunisia.
Tahia
T
Sellami-Boudawara
Laboratory of Molecular Biotechnology of Eukaryotic, Center of Biotechnology of Sfax, University of Sfax, Sfax, Tunisia.
Ali
A
Gargouri
Laboratory of Molecular Biotechnology of Eukaryotic, Center of Biotechnology of Sfax, University of Sfax, Sfax, Tunisia.
Raja
R
Mokdad-Gargouri
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D000328:Adult; D000368:Aged; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D014416:Tunisia
D051546:Cyclooxygenase 2
COX-2; gastric carcinoma; immunohistochemistry; prognosis