Inappropriate retinoic acid receptor-beta expression in oral dysplasias: correlation with acquisition of the immortal phenotype.

Retinoids are useful in the treatment of premalignant oral lesions and in preventing the occurrence of second primary cancers after resection of the initial primary oral cancer, but long-term prognosis is still poor, presumably due to malignant cells escaping retinoid control. Previous work has shown that loss of expression of retinoic acid receptor beta is one of the most consistent molecular changes during oral cancer progression in vivo. In this report we demonstrate, using a novel panel of primary cultures of oral lesions, that loss of retinoic acid receptor beta expression at the dysplasia stage occurs during the transition from senescent to immortal phenotype but may occur independently to the loss of CDKN2A/p16 expression.