Differential expression of nuclear retinoid receptors in normal, premalignant, and malignant head and neck tissues.

ABSTRACT

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 nuclear 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 riboprobes of RAR-alpha, RAR-beta, RAR-gamma, RXR-alpha, and RXR-beta 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-gamma and RXR-alpha and RXR-beta mRNAs were detected in most of the adjacent normal, hyperplastic, dysplastic, and malignant tissues. RAR-alpha mRNA was detected in 94% of adjacent normal tissues and hyperplastic tissues, in 87% of dysplasias, and in 77% of HNSCCs. In contrast, RAR-beta 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-beta level in carcinoma and adjacent normal tissues was significant (P < 0.05). These results indicate that the decreased expression of RAR-beta may be associated with HNSCC development.