Expression of RAR alpha and RAR beta in human oral potentially malignant and neoplastic lesions

Retinoids reverse potentially malignant lesions and inhibit the development of second primary cancers in patients with head-and-neck cancer. Many of t he effects of retinoids result From modulation of gene expression by 2 dist inct classes of nuclear receptor, RARs and RXRs; alterations in their expre ssion can lead to tumorigenesis, To determine whether aberrations in expres sion of the receptors are related to the development of betel- and tobacco- related oral cancer, we used specific monoclonal antibodies against RAR alp ha and RAR beta to detect expression of these proteins in 30 histopathologi cally normal tissues, 45 potentially malignant lesions (leukoplakia) with h istological evidence of either hyperplasia (31 cases) or dysplasia (14 case s) and 64 oval squamous-cell carcinomas (SCCs) by immunohistochemistry. Of the 30 normal oral tissues analysed, 8 cases showed detectable levels of RA R alpha protein, while 10 cases did not show detectable RAR beta immunoreac tivity, Immunostaining for RAR alpha protein was observed in 12/31 (39%) hy perplastic lesions, 6/14 (43%) dysplastic lesions and 43/64 (67%) oral SCCs , Expression of RARa in oral SCC war significantly associated with the hist ological differentiation status of tumours (p = 0.016), In contrast, lack o f detectable immunoreactivity was observed in 19/31 (61%) hyperplastic lesi ons, 8/14 (57%) dysplastic lesions and 21/64 (33%) oral SCCs, The hallmark of the study was the significant increase in RAR alpha immunopositivity in oral SCCs compared to normal tissue (p = 0.0005) and hyperplastic lesions ( p = 0.016), One intriguing feature was the significant decrease in RAR beta immunopositivity in hyperplastic lesions compared with normal oral mucosa (p = 0.05) as well as in oral SCCs compared with normal tissues (p = 0.0008 ). (C) 2001 Wiley-Liss, Inc.