Cyclooxygenase-2 expression correlates with poor prognosis in pancreatic cancer

Abstract

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.

Synergistic Effects of Exemestane and Aspirin on MCF-7 Human Breast Cancer Cells

“…After treatment cells were harvested and lysed, and equal aliquots of extracted protein were analyzed for Bcl-2 expression by Western blotting. The levels of β-actin were also measured as a normalization control 2002; Juuti et al, 2006). Although COX-1 is present at a constant level in most cells and tissues, previous studies have shown that COX-1 is highly expressed in several types of tumors,including breast cancer (Chulada et al, 2000;Kirschenbaum et al, 2000;Connolly et al, 2002;Sales et al, 2002;Gupta et al, 2003;Daikoku et al, 2005;Daikoku et al, 2006;Daikoku et al, 2007;Erovic et al, 2008).…”

Reclassification of tumour origin in resected periampullary adenocarcinomas reveals underestimation of distal bile duct cancer

“…Although the patients groups in these studies are larger than in our study, the methodological differences in the selection of patients and / or immunohistochemical techniques employed, raise some doubts on the results of these studies. In the study of Juuti 102 , more than 30 years old specimens were included. It is well known that for immunohistochemical staining protocol, aging of the fixed tumour tissue might interfere with staining process 168 .…”

Prolonged systemic circulation of chimeric oncolytic adenovirus Ad5/3-Cox2L-D24 in patients with metastatic and refractory solid tumors

“…Tumors likely to be Cox-2 positive and defective in the p16/Rb pathway were included. 51,52,15 Other oncological treatments were not administered concurrently. Exclusion criteria were organ transplant, HIV, severe cardiovascular, metabolic, or pulmonary disease (for example, symptomatic coronary heart disease, uncontrolled blood pressure).…”