Differential expression of two new members of the p53 family, p63 and p73, in extramammary Paget's disease.
BACKGROUND
The proteins p53, p63 and p73 are known to be overexpressed and to play important roles in the pathogenesis of many tumours, but the expression of p63 and p73 has not previously been investigated in extramammary Paget's disease (EMPD).


OBJECTIVE
To investigate the potential contribution of p53, p63 and p73 in the pathogenesis of EMPD.


METHODS
In total, 35 paraffin wax-embedded tissue samples from patients with EMPD were examined using immunohistochemical staining for p53, p63 and p73.


RESULTS
All of the 35 EMPD specimens, including all 6 invasive EMPD and 2 metastatic lymph-node specimens, showed nuclear overexpression of both p53 and p73. The expression levels (percentage of positive cells) of p53 and p73 (90.66 +/- 12.53% and 80.20 +/- 13.07%) in EMPD were significantly higher than those of normal skin. There was a significant correlation between the expression levels of p53 and p73 in EMPD. In 29 of 35 EMPD specimens, there was no nuclear expression of p63, and weak or moderate staining was found in only 6 specimens. The expression level of p63 in EMPD was significantly less than that in normal skin.


CONCLUSIONS
Our study shows that the concordant overexpression of p53 and p73 and the decreased expression of p63 may play a pivotal role in the pathogenesis of EMPD. The decreased expression of p63 may play a more important role in the pathogenesis of EMPD than the overexpression of p53 and p73.
Chen
S
S
Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Moroi
Y
Y
Urabe
K
K
Takeuchi
S
S
Kido
M
M
Hayashida
S
S
Uchi
H
H
Uenotsuchi
T
T
Tu
Y
Y
Furue
M
M
D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010145:Paget Disease, Extramammary / Q000235:genetics* / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D013223:Statistics as Topic; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C115051:TP63 protein, human; C000606460:TP73 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins