Loss of retinoic acid receptor-β expression is an early event during esophageal carcinogenesis

We recently observed that growth inhibition of esophageal cancer cells by retinoic acid (RA) was associated with both constitutive expression and RA-induced up-regulation of RA receptor β (RAR-β). Cell lines that did not express RAR-β were also resistant to RA. To explore the expression of RAR-β mRNA in vivo, we analyzed esophageal tissue specimens from 16 normal mucosae, 30 dysplastic lesions, and 157 esophageal tumors by in situ hybridization. RAR-β was detected in 880/o (14/16) of normal esophageal tissues and in 96% (96/100) of distant normal esophageal mucosa from cancer specimens. In contrast, RAR-β was expressed in only 570/o (17/30) of dysplastic lesions and in 540/o (84/157) of carcinomas. Among esophageal carcinomas RAR-β mRNA was expressed in 62% (26/42) of well-differentiated, 54% (27/50) of moderately differentiated, and only 29% (4/14) of poorly differentiated SCCs. Our data suggest that the loss of RAR-β expression is an early event associated with esophageal carcinogenesis and the status of squamous differentiation.