Immunohistochemical Study of p53 and MDM2 Expression on the Epithelial Tumors of the Skin

Cho, Han Suk; Park, Eun Joo; Kim, Chul Woo; Cho, Hee Jin; Kim, Kwang Ho; Kim, Kwang Joong; Park, Hye Rim

Abstract

BACKGROUND: MDM2 (mouse double minute 2), the product of an oncogene is a key regulator of p53. It can repress transcription of p53 and eliminate it through proteolytic degradation. On the other hand, p53 binds specifically to the MDM2 and stimulates its transcription. Thus the two molecules are linked to each other through an autoregulatory feedback loop.
OBJECTIVE
To evaluate the expression patterns of p53 and MDM2 in several epithelial tumors and assess their correlations.
METHODS
We investigated the expression of p53 and MDM2 protein by an immunohistochemical method on formalin-fixed, paraffin-embedded tissue specimens of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), Bowen's disease, and actinic keratosis (AK).
RESULTS
The expression of p53 was increased in 83.3% (15/18) of BCC, 87.5% (14/16) of SCC, 75.0% (12/16) of Bowen's disease, and 57% (8/14) of AK. The expression of MDM2 was increased in 50.0% (9/18) of BCC, 25.0% (4/16) of SCC, 68.8% (11/16) of Bowen's disease, and 14.3% (2/14) of AK. The expression level of p53 had a significant positive correlation with the expression level of MDM2 in actinic keratosis (p=0.022). There was no correlation between the expression level of these two markers in others (p>0.05).
CONCLUSION
This data suggests that p53 and MDM2 may be associated with pathogenesis of skin epithelial tumors with complex pathways. p53 (+)/MDM2 (+) phenotype expression may have an important pathogenetic role in Bowen's disease. p53 (+)/MDM2 (-) type expression may have an important pathogenetic role in BCC, SCC, and AK. In particular, in AK p53 (+)/MDM2 (-) phenotype expression may have a major pathogenetic role. The mechanism of how they interact to promote tumorigenesis and the prognostic values in skin epithelial tumors remains to be elucidated though.