Cyclooxygenase-2 expression correlates with poor prognosis in pancreatic cancer.
BACKGROUND
Cyclooxygenase-2 (COX-2) overexpression is related to poor outcome in several cancers. COX-2 is upregulated in 42-90% of pancreatic ductal adenocarcinomas and is a potential target for chemotherapy. Earlier studies have not shown the expression of COX-2 to be a prognostic factor in pancreatic cancer.


OBJECTIVE
To evaluate the prognostic value of COX-2 in a series of patients with pancreatic adenocarcinoma.


METHODS
128 patients operated on for pancreatic adenocarcinoma at Helsinki University Central Hospital between 1974 and 1998 provided sections from primary tumours which were immunohistochemically stained with a COX-2-antihuman monoclonal antibody.


RESULTS
Cytoplasmic COX-2 reactivity (>5%) occurred in 46 specimens (36%), correlating neither with age, sex, stage, size, tumour stage, nodal metastases, nor grade. Lack of COX-2 expression correlated with distant metastases (p = 0.026). In univariate survival analysis, COX-2 expression (p = 0.0114), stage (p = 0.0002), grade (p = 0.0001), and age (p = 0.042) had prognostic significance. One, two, and five year survival rates were 51%, 32%, and 8% in the COX-2 negative groups compared with 34%, 5%, and 5% in the COX-2 positive groups (p = 0.011). Prognostic significance was especially high for patients operated on with curative intent (p = 0.004). In multivariate analysis, COX-2 was an independent prognostic factor (hazard ratio = 1.6 (95% confidence interval, 1.1 to 2.3)).


CONCLUSIONS
Expression of COX-2 was associated with poor outcome from pancreatic ductal adenocarcinoma and was independent of tumour stage, grade, or age in multivariate analysis.
Juuti
A
A
Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland.
Louhimo
J
J
Nordling
S
S
Ristimäki
A
A
Haglund
C
C
D000230:Adenocarcinoma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000367:Age Factors; D000368:Aged; D016009:Chi-Square Distribution; D051546:Cyclooxygenase 2 / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D012680:Sensitivity and Specificity; D012737:Sex Factors; D015996:Survival Rate
D009363:Neoplasm Proteins; D051546:Cyclooxygenase 2