Frequent CpG methylation of ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) in sporadic and hereditary Tunisian breast cancer patients: clinical significance.

Aberrant methylation of the CpG islands in promoter regions is one of the mechanisms for inactivation of tumor suppressor genes in many human cancers including breast carcinoma. In this study, we aimed to assess, by methylation-specific PCR, the CpG methylation pattern of the UCHL1 promoter in 94 sporadic and 44 hereditary breast cancers from Tunisian patients. The percentage of UCHL1 methylation was 67 % in sporadic and 82 % in hereditary breast cancer cases. In sporadic cases, UCHL1 methylation correlated with poor response to treatment (P = 0.042) and progesterone receptor status (P = 0.036), whereas in patients with hereditary predisposition, the only significant association was found with Her2 expression (P = 0.024). Moreover, in patients with sporadic breast cancer, the UCHL1 unmethylated pattern conferred a prolonged overall survival time in particular in the group of patients with advanced TNM stage of the disease (P log rank = 0.04). Aberrant CpG methylation of the UCHL1 promoter was significantly associated with transcriptional silencing of this tumor suppressor gene in sporadic breast cancer tissues (P = 0.001). On the other hand, the UCHL1 unmethylated pattern correlated with P53 positivity in primary sporadic tumors (P = 0.032), supporting the functional link between the two tumor suppressors in breast tumorigenesis.