Introduction and Objectives
Nuclear Factor κ-B (NFκB) is the ‘supervisor’ protein of chronic inflammation and malignant transformation. NFκB remains in the cytoplasm transcriptionally silent. Activation of NFκB in response to extracellular stimuli lead to translocation to the nucleus and activation of transcription of a plethora of genes, involved in tumor promotion and proliferation. Our objective was to evaluate the expression of NFκB in Transitional Cell Carcinoma of the bladder and its correlation with histological Grade and clinicopathological parameters.
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 NFκB was used. A molecular profile was created for each patient and the induction or downregulation of nuclear and cytoplasmic NFκB expression was evaluated and documented. Relationship between NFκB and Grades of carcinogenesis were evaluated by Spearman's rank correlation coefficient and validated by Fisher's exact test.
NFκB signal was both cytoplasmic and nuclear. NFκB cytoplasmic expression was undetectable in 6.9% (2/29) of specimens of normal epithelium and overexpressed in 38.9% (7/29). On the other hand, none of the well differentiated tumors and only 3.3% (1/30) of moderate and 1.8% (1/54) of poor differentiated carcinomas showed negative NFκB cytoplasmic staining. Statistical analysis revealed a negative correlation between cytoplasmic molecular expression and grades of differentiation. As normal cells progressively gained atypical characteristics the cytoplasmic expression of NFκB has been downregulated. As far as nuclear staining of NFκB is concerned, 100% (29/29) of normal transitional epithelium lacked nuclear staining. Only in 13% (7/54) of poorly differentiated carcinomas there was no nuclear staining and 26% (14/54) of them showed strong immunoreactivity. Statistical analysis revealed a strong positive association between histological grade and nuclear expression of NFκB (test of trend p-value <0.001). No association with age or gender was observed.
Our results indicate an induction of this key molecule along the carcinogenesis path and the level of differentiation. Although inflammation has long been known as a localized protective reaction of tissue, there has been a new realization about its role in cancer. These observations imply that anti-inflammatory agents that suppress NFκB should have a potential role in bladder cancer chemoprevention.
© 2009 European Association of Urology. Published by Elsevier Inc. All rights reserved.