Lack of correlation between expression of retinoic acid receptor-beta and loss of heterozygosity on chromosome band 3p24 in esophageal cancer.

Loss of heterozygosity (LOH) on chromosome arm 3p occurs frequently in human cancers, including esophageal cancer, suggesting that tumor suppressor genes may be located on this chromosome arm. The retinoic acid receptor-beta (RARB) gene is localized on chromosome band 3p24, and its expression is progressively lost during esophageal carcinogenesis. Furthermore, growth inhibition of esophageal cancer cell lines by all-trans retinoic acid has been associated with the constitutive and induced expression of RARB. We therefore assessed LOH on chromosome arm 3p and RARB expression in esophageal cancer to investigate the mechanism of altered RARB expression during carcinogenesis. We first analyzed LOH in 65 paired surgical specimens of normal mucosa and esophageal cancer by using 10 microsatellite markers, which resulted in 44 informative cases for subsequent study. LOH on chromosome band 3p24 was found to occur at an overall rate of 36.4% (16/44) by three markers (D3S1293, THRB, and D3S1283). LOH for these three individual markers was 14.0%, 47.4%, and 20.9%, respectively. Meanwhile, RARB expression was lost in 43.2% (19/44) of these 44 samples. The loss of RARB expression was not correlated with LOH on chromosome band 3p24 (gamma = -0.22, -0.069, and -0.02, P = 0.15, 0.78, and 0.9 for D3S1293, THRB, and D3S1283, respectively), although both altered RARB expression and LOH in esophageal cancer were statistically significant (P = 0.001 and 0.0001, respectively), indicating that the loss of RARB expression cannot be explained by LOH on 3p24.