S. Agarwal et al., MDM2/p53 co-expression in oral premalignant and malignant lesions: potential prognostic implications, ORAL ONCOL, 35(2), 1999, pp. 209-216
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.