Overexpression of transforming growth factor-beta3 immunohistochemical staining in extramammary Paget's disease, but downregulated expression in Bowen's disease.
BACKGROUND
The role of transforming growth factor-beta (TGF-beta) in carcinogenesis is complex, with some reports indicating a tumor inhibition role and others indicating a tumor promotion role. In particular, TGF-beta3 is thought to play a key role in controlling epithelial homeostasis. Immunopositive p53 has been demonstrated in a variety of human malignant tumors and its role in oncogenesis and tumor progression is thought to be important. Extramammary Paget's disease (EPD) and Bowen's disease are skin cancers of unknown histogenesis.


OBJECTIVE
To clarify the role of TGF-beta3 and p53 in EPD and Bowen's disease and to better understand the origin of these disorders.


METHODS
Specimens were obtained from 12 patients with EPD and 12 patients with Bowen's disease seen at our clinic between 1993 and 2000. TGF-beta3 and p53 immunohistochemical staining was performed.


RESULTS
In three of the 12 EPD patients and five of the 12 Bowen's disease patients, positive p53 staining was detected. In contrast, TGF-beta3 overexpression was detected in all EPD patients, whereas downregulated TGF-beta3 expression was detected in all Bowen's disease patients.


CONCLUSIONS
The present data suggest different roles for TGF-beta3 in abnormal epidermal cells in EPD and Bowen's disease. Thus, TGF-beta3 expression may be modulated differently via a p53-dependent or -independent pathway in the pathogenesis of EPD and Bowen's disease. Moreover, high TGF-beta expression appears to be a useful indicator of tumor activity in EPD.
Kawakami
T
T
Department of Dermatology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki City, Kanagawa 216-8511, Japan. tami@marianna-u.ac.jp
Soma
Y
Y
Mizoguchi
M
M
Saito
R
R
D000368:Aged; D000369:Aged, 80 and over; D001913:Bowen's Disease / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010145:Paget Disease, Extramammary / Q000378:metabolism / Q000473:pathology*; D012867:Skin / Q000737:chemistry / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D053782:Transforming Growth Factor beta3; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D016212:Transforming Growth Factor beta; D053782:Transforming Growth Factor beta3; D016159:Tumor Suppressor Protein p53