DETECTION OF P53 AND MDM2 PROTEIN EXPRESSION IN HEAD AND NECK CARCINOGENESIS

Hyperplastic lesions of the oropharyngeal mucosa such as leukoplakia a nd oral lichen planus can eventually develop into squamous cell carcin omas (SCC) and provide an excellent model for multistage carcinogenesi s. The development of carcinomas is assumed to be the result of the in teraction of genetic factors, locally applied carcinogens and immunolo gical unresponsiveness. Recently a novel gene termed mdm2 has been iso lated that is found to be involved in transcriptional regulation and c an inhibit p53 function by forming a complex with p53. In this study t he immunohistochemical detection of the MDM2 protein in 186 paraffin e mbedded tissue sections of normal mucosa, premalignant, malignant and metastatic lesions of the oropharyngeal mucosa is reported for the fir st time, p53 protein expression was also investigated in the same tiss ue samples. The increase in the number of p53 and MDM2 positive biopsi es was correlated with the dysplasia grade and the loss of differentia tion in the premalignant and malignant lesions. In late stages of the disease the number of biopsies that expressed both p53 and MDM2 increa sed. Inactivation of p53 function in head and neck carcinogenesis may also be due to MDM2 binding. Detection of MDM2 protein expression by i mmunohistochemistry may be an important diagnostic tool in the future.