Loss of heterozygosity, allele silencing and decreased expression of p73 gene in breast cancers: Prevalence of alterations in inflammatory breast cancers

The p73 gene is a p53 homologue located at 1p36-33, a region submitted to d eletions in breast cancer (BC) and putatively imprinted. To study whether p 73 was associated with breast carcinogenesis, loss of heterozygosity (LOH), allele expression and transcript levels were assessed in 59 BC, including 39 BC presenting no inflammatory symptoms (NBC) and 20 inflammatory BC (IBC ). IBC is a rare but aggressive form of cancer with a very Door prognosis. Normal breast epithelium (BE) and lymphocytes from patients were used as co ntrols. StyI polymorphism generating GC and/or AT alleles was used to selec t 22 heterozygous patients, p73 LOH was significantly higher in IBC than in NBC [five of eight cases (62%) versus two of 14 cases (14%); Fisher's exac t test, P = 0.05]. p73 was biallelically expressed in all BE. In contrast, 12 of 16 (75%) BC were monoallelically expressed, showing that allele silen cing was significantly associated with breast carcinogenesis (P = 0.012), A T being the preferential silent allele (10 out of 12 tumours). p73 mRNA lev els in NBC and IBC were two- and threefold lower than in BE, respectively, suggesting that decreased expression could be related to tumour aggressiven ess. In conclusion, LOH, allele silencing and decreased expression of the p 73 gene may play a role in breast carcinogenesis.