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

We recently observed that growth inhibition of esophageal cancer cells by r etinoic acid (RA) was associated with both constitutive expression and RA-i nduced up-regulation of RA receptor beta (RAR-beta). Cell lines that did no t express RAR-beta were also resistant to RA. To explore the expression of RAR-beta mRNA in vivo, we analyzed esophageal tissue specimens from 16 norm al mucosae, 30 dysplastic lesions, and 157 esophageal tumors by in situ hyb ridization. RAR-beta was detected in 88% (14/16) of normal esophageal tissu es and in 96% (96/100) of distant normal esophageal mucosa from cancer spec imens. In contrast, RAR-beta was expressed in only 57% (17/30) of dysplasti c lesions and in 54% (84/157) of carcinomas. Among esophageal carcinomas RA R-beta mRNA was expressed in 62% (26/42) of wed-differentiated, 54% (27/50) of moderately differentiated, and only 29% (4/14) of poorly differentiated SCCs. Our data suggest that the loss of RAR-beta expression is an early ev ent associated with esophageal carcinogenesis and the status of squamous di fferentiation.