title: Cyclooxygenase-2 expression in bladder cancer and patient prognosis: results from a large clinical cohort and meta-analysis.
abstract: Aberrant overexpression of cyclooxygenase-2 (COX2) is observed in urothelial carcinoma of the bladder (UCB). Studies evaluating COX2 as a prognostic marker in UCB report contradictory results. We determined the prognostic potential of COX2 expression in UCB and quantitatively summarize the results with those of the literature through a meta-analysis. Newly diagnosed UCB patients recruited between 1998-2001 in 18 Spanish hospitals were prospectively included in the study and followed-up (median, 70.7 months). Diagnostic slides were reviewed and uniformly classified by expert pathologists. Clinical data was retrieved from hospital charts. Tissue microarrays containing non-muscle invasive (n=557) and muscle invasive (n=216) tumours were analyzed by immunohistochemistry using quantitative image analysis. Expression was evaluated in Cox regression models to assess the risk of recurrence, progression and disease-specific mortality. Meta-hazard ratios were estimated using our results and those from 11 additional evaluable studies. COX2 expression was observed in 38% (211/557) of non-muscle invasive and 63% (137/216) of muscle invasive tumors. Expression was associated with advanced pathological stage and grade (p<0.0001). In the univariable analyses, COX2 expression - as a categorical variable - was not associated with any of the outcomes analyzed. As a continuous variable, a weak association with recurrence in non-muscle invasive tumors was observed (p-value=0.048). In the multivariable analyses, COX2 expression did not independently predict any of the considered outcomes. The meta-analysis confirmed these results. We did not find evidence that COX2 expression is an independent prognostic marker of recurrence, progression or survival in patients with UCB.
authors.affiliation: Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: Maciej J
authors.initials: MJ
authors.lastname: Czachorowski
authors.forename: André F S
authors.initials: AF
authors.lastname: Amaral
authors.forename: Santiago
authors.initials: S
authors.lastname: Montes-Moreno
authors.forename: Josep
authors.initials: J
authors.lastname: Lloreta
authors.forename: Alfredo
authors.initials: A
authors.lastname: Carrato
authors.forename: Adonina
authors.initials: A
authors.lastname: Tardón
authors.forename: Manuel M
authors.initials: MM
authors.lastname: Morente
authors.forename: Manolis
authors.initials: M
authors.lastname: Kogevinas
authors.forename: Francisco X
authors.initials: FX
authors.lastname: Real
authors.forename: Núria
authors.initials: N
authors.lastname: Malats
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012307:Risk Factors; D046888:Tissue Array Analysis; D001749:Urinary Bladder Neoplasms / Q000201:enzymology* / Q000473:pathology; D055815:Young Adult
chemical_list: D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human