MDM2/p53 co-expression in oral premalignant and malignant lesions: potential prognostic implications

The expression of MDM2 protein in betel and tobacco related oral malignanci es in Indian population, its relationship to clinicopathological parameters and p53 protein expression was investigated. Sixty five oral squamous cell carcinomas (SCCs), 33 premalignant lesions (leukoplakia) and 30 normal ora l tissues were assessed by immunohistochemical analysis. MDM2 protein was o verexpressed in 51/65 (78%) oral SCCs and 17/33 (52%) premalignant lesions; 11/23 hyperplastic lesions and 6/10 dysplastic lesions. mdm2 gene amplific ation is an infrequent event in oral tumorigenesis. Elevation in the level of MDM2 protein not only in oral SCCs but also in premalignant lesions sugg ests that altered MDM2 expression is an early event in the pathogenesis of oral neoplasia. The hallmark of the study was the significant association o f MDM2 expression with the p53 protein accumulation in 16/33 (49%) oral pre malignant lesions (p = 0.001) and 39/65 (60%) malignant lesions (p = 0.021) , suggesting an active role for MDM2 in binding and inactivating p53 in ora l tumorigenesis. Further, significant association of MDM2/p53 co-expression was observed with advanced tumour stage (p = 0.0009), as well as lymph nod e metastasis (p = 0.0325) features associated with aggressive tumour behavi our and poor prognosis. Discordant MDM2 + /p53-phenotype was observed in 12 /65 (18%) oral SCCs suggesting a p53-independent role for MDM2 in the patho genesis of a subset of oral carcinomas. In conclusion, alterations in MDM2 and p53 expression are early events likely to be involved in preinvasive st ages in oral tumorigenesis and may be indicative of a 'gain of function' ph enotype with more aggressive characteristics. (C) 1999 Elsevier Science Ltd . All rights reserved.