Prognostic Significance of TIMP3 Hypermethylation in Post-treatment Salivary Rinse from Head and Neck Squamous Cell Carcinoma Patients
Menée sur 200 patients atteints d'un carcinome épidermoïde de la tête et du cou traité entre 2006 et 2008, cette étude évalue, du point de vue de la survie sans récidive locale, la valeur pronostique de la détection, après traitement et dans la salive, d'une hyperméthylation du gène TIMP3
Hypermethylation in the promoter regions of genes is associated with suppression of gene expression and has been considered a potential molecular marker for several tumor types, including Head and Neck Squamous Cell Carcinomas (HNSCC). Moreover, hypermethylation can be detected in body fluids such as saliva and can be useful for the diagnosis and prognosis of patients suffering from cancer. To evaluate the hypermethylation profile as a tool for early detection of tumor recurrences, this study determine the methylation status of 24 genes in salivary rinses collected from HNSCC patients at diagnosis, just after the last curative treatment and in the patients’ follow up visit at six months after treatment. In the analysis of salivary rinse samples taken at diagnosis of HNSCC patients, 5 genes (CCNA1, DAPK, DCC, MGMT and TIMP3) showed high specificity and sensitivity. Hypermethylation in any of these five genes was correlated with the presence of tumors in the oral cavity. Patients with TIMP3 methylation in samples collected six months after the last curative treatment had lower local recurrence-free survival (p = 0.008). Multivariate analysis confirmed that this hypermethylation pattern remained as an independent prognostic factor for local recurrence (p = 0.025). This study presents, for the first time, the detection of TIMP3 promoter hypermethylation in post-treatment salivary rinse as an independent prognostic maker for local recurrence-free survival in patients with HNSCC, justifying the use of DNA hypermethylation detection in saliva as a tool for identifying and monitoring HNSCC patient’s subgroups with high risk of developing local recurrence.
Carcinogenesis , résumé, 2012