Analysis of p53, p21Waf1/Cip1 and TGF-β3 Immunohistochemical Staining in Bowen’s Disease

Abstract

Background: The p53 gene is one of a family of tumor suppressor genes that have been implicated in the genesis of a wide variety of malignant neoplasms including Bowen’s disease. Its role in oncogenesis and tumor progression is thought to be of importance. Transforming growth factor β (TGF-β) is the most potent known inhibitor of the progression of normal epithelial cells through the cell cycle. p21^Waf1/Cip1 is thought to mediate p53 signaling induced by DNA-damaging agents to arrest the cell cycle. Objective: The present study evaluates the expression of p53, p21^Waf1/Cip1 and TGF-β₃ protein and speculates on their role in Bowen’s disease. Methods: Sixteen patients seen at our clinic between 1993 and 2000 were examined. We analyzed p21^Waf1/Cip1, p53 and TGF-β₃ immunohistochemical staining in all specimens. Results: In 7 of the Bowen’s disease patients, overexpression of p53-positive cells was present in the middle and basal layers, and intense staining of p21^Waf1/Cip1 was observed in the upper spinous layers. In the other 9 Bowen’s disease patients, we found positively stained cells for p21^Waf1/Cip1 but negative p53 immunostaining in the upper epidermal layer. Downregulated TGF-β₃ expression was detected in all layers except the upper spinous layers. Conclusion: These observations suggest different roles for p21^Waf1/Cip1 and p53 within abnormal cells in Bowen’s disease. p21^Waf1/Cip1 may induce terminal differentiation to the superficial layer in Bowen’s disease via either a p53-independent or -dependent pathway. Moreover, downregualtion of TGF-β₃ immunostaining provides relevant information concerning the pathogenesis of Bowen’s disease.