LOSS OF RETINOIC ACID RECEPTOR-BETA EXPRESSION IN BREAST-CANCER AND MORPHOLOGICALLY NORMAL ADJACENT TISSUE BUT NOT IN THE NORMAL BREAST-TISSUE DISTANT FROM THE CANCER

Retinoids and their receptors [retinoic acid receptors (RARs) and reti noid X reccptors] play an important role in maintaining the balance be tween proliferation and apoptosis, Recently, Deng et al, [Science (Was hington DC), 274: 2057-2059, 1996] reported a loss of heterozygosity o n chromosome 3p24 in breast cancer specimens and the morphologically n ormal appearing adjacent tissue, The 3p24 locus includes, among other genes, the region coding for RAR-beta. This study was designed to dete rmine whether there are abnormalities in the expression of retinoid re ceptors in surgical specimens of patients with breast cancer, In 14 pa tients, transcripts of nuclear retinoid receptors were detected by in situ hybridization in formalin-fixed, paraffin-embedded specimens by m eans of digoxigenin-labeled riboprobes specific for RAR-alpha, -beta a nd -gamma. We found RAR-alpha expressed in all specimens, whereas RAR- gamma was expressed in 100% of normal breast tissue but in only 11 of 14 tumorous lesions, RAR-beta was found in all cases of normal breast tissue localized distant from the tumor, but in 13 of 14 eases it was completely absent in the tumor and the morphologically normal appearin g tissue adjacent to the tumor, One possibility to explain the suppres sion of RAR-beta is a mutation in the promoter region, Sequencing the DNA extracted from paraffin-embedded tumor tissue of the corresponding breast cancer specimens, we were not able to detect any mutation in t he retinoic acid-responsive element. Our results clearly indicate a cr ucial role of RAR-beta in the carcinogenesis of breast cancer.