Anti-Retinoic Acid (RA) Antibody Binding to Human Premalignant Oral Lesions, Which Occurs Less Frequently Than Binding to Normal Tissue, Increases after 13-cis-RA Treatment in Vivo and Is Related to RA Receptor β Expression

Nuclear retinoic acid receptor β (RAR-β ) expression decreases in human premalignant oral lesions (POLs). RAR-β suppression could result from a decrease in the cellular level of retinoids because RAR-β gene transcription is enhanced by retinoids. To explore this hypothesis, we compared the binding of a monoclonal antibody (mAb) against all-trans-retinoic acid (RA; anti-RA mAbs) to normal oral tissue and POLs. All 7 normal specimens stained positive with the antibody compared to only 20 of 43 POLs; similarly, 7 of 7 normal specimens contained RAR-β mRNA compared to only 14 of 43 POLs. Twenty-four specimens were available before and after a 3-month treatment with 13-cis-RA in vivo. Anti-RA mAb binding to these specimens increased from 10 of 24 before to 22 of 24 after treatment, and the expression of RAR-β mRNA increased from 7 of 24 before to 21 of 24 after treatment, respectively. There was a strong agreement between the binding of anti-RA mAbs and the expression of RAR-β. Thus, we propose that the binding of anti-RA mAbs reflects the level of retinoids in the tissues and that this level is related strongly to RAR-β expression.