Introduction and Objectives
Accumulated evidence indicates that carcinogenesis is closely associated with the transformation of normal stroma into a ‘reactive’ stromal phenotype. The present study investigates the role of COX-2 – an enzyme that catalyzes the synthesis of prostaglandins – in this stromal remodeling by evaluating and comparing the expression in stromal myofibroblasts that surround normal transitional epithelium and carcinomas.
Material and Methods
Immunohistochemical methodology was performed on formalin-fixed, paraffin-embedded sections from urinary bladder carcinomas of 140 patients (94 males (67.1%) and 46 females (32.9%), who underwent curative transurethral resection. The patients’ age ranged from 23 to 90 years, (mean age = 70 years). Their diagnoses were reported as follows: Grade I n = 27(19.3%), Grade II n = 30(21.4%), and Grade III n = 54(38.6%). 29(20.7%) cases of normal bladder epithelium were selected from patients that underwent diagnostic biopsies. Monoclonal antibody against the human Cox-2 molecule was used. A molecular profile was created for each patient and the induction or downregulation of Cox-2 expression was evaluated and documented. Relationship between Cox-2 and grades of carcinogenesis were evaluated by Spearman's rank correlation coefficient and validated by Fisher's exact test.
Myofibroblasts surrounding normal epithelium showed no cytoplasmic immunoreactivity in 41.4%, and only 6.9% overexpressed this enzyme. 63% of myofibroblasts surrounding carcinomas presented with moderate and strong immunoreactivity, and only 12.6% had no staining. The Spearman rank correlation coefficient (rs) revealed a positive correlation (r = 0.29, p-value = 0.001), meaning that COX- 2 is overexpressed in myofibroblasts surrounding bladder carcinomas. Furthermore positive correlation has been revealed when Spearman rank correlation coefficient (rs) performed for Grades of carcinogenesis (normal–Grade I, r = 0.30, p-value = 0.026, Grade I–Grade II, r = 0.31, p-value = 0.018, Grade II–Grade III, r = 0.38, p-value <0.001).
COX-2 expression is upregulated in stromal myofibroblasts surrounding bladder carcinomas compared to normal transitional epithelium. This study emphasizes that the role of COX-2, which is important molecular target of chemoprevention, is not only confined to the tumor epithelial cells but is also extended in the stroma especially in the stromal myofibroblasts, which are important players in the process of bladder carcinogenesis.
© 2009 European Association of Urology. Published by Elsevier Inc. All rights reserved.