Retinoids reverse premalignant lesions and inhibit the development of second primary cancers in patients with upper aerodigestive tract

Retinoids reverse premalignant lesions and inhibit the development of second primary cancers in patients with upper aerodigestive tract cancers. It is thought that these effects result from the ability of retinoids to restore normal cell growth and differentiation. Since flu clear retinoid receptors (RARs and RXRs) are the ultimate mediators of retinoid actions, alterations in their expression could lead to cancer development. To determine whether the expression of the mRNAs of the receptors is related to the development of head and neck squamous cell carcinoma (HNSCC), we used digoxigenin-labeled antisense ribo probes of RAR-a, RAR-@3,RAR-@y, RXR-a, and RXR-fi for in situ hybridization to histological sections of specimens from 7 normal volunteers and 31 HNSCC patients. All 31 tissue specimens contained carcinomas, 16 also contained dysplastic lesions, 22 also contained hyperplastic lesions, 17 also contained adjacent normal tissue, and 6 contained all 4 types of tissue. All specimens from normal volunteers expressed the 5 receptors. Similar levels of RAR-y and RXR-a and RXR-@3mRNAs were detected in most of the adjacent normal, hyper plastic, dysplastic, and malignant tissues. RAR.a mRNA was detected in 94% of adjacent normal tissues and hyperplastic tissues, in 87% of dysplasias, and in 77% of HNSCCs. In contrast, RAR-ji mRNA was detected in about 70% of adjacent normal and hyperplastic lesions, and its expression decreased further to 56% of dysplastic lesions and to 35% of HNSCCs. The difference in RAR-fi level in carcinoma and adjacent normal tissues was significant (P < 0.05). These results mdi cate that the decreased expression of RAR-@3may be associated with HNSCC development.