Analysis of p53, p21(Waf1/Cip1) and TGF-beta(3) immunohistochemical staining in Bowen's disease.
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 beta (TGF-beta) 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-beta(3) 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-beta(3) 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-beta(3) expression was detected in all layers except the upper spinous layers.


CONCLUSIONS
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-beta(3) immunostaining provides relevant information concerning the pathogenesis of Bowen's disease.
Department of Dermatology, St. Marianna University School of Medicine, Kawasaki, Japan. tami@marianna-u.ac.jp
T
T
Kawakami
Y
Y
Soma
M
M
Mizoguchi
R
R
Saito
D000368:Aged; D000369:Aged, 80 and over; D001913:Bowen's Disease / Q000378:metabolism* / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000737:chemistry / Q000473:pathology; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000032:analysis*; D053782:Transforming Growth Factor beta3; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016212:Transforming Growth Factor beta; D053782:Transforming Growth Factor beta3; D016159:Tumor Suppressor Protein p53