Prognostic significance of TIMP3 hypermethylation in post-treatment salivary rinse from head and neck squamous cell carcinoma patients

Author(s)

Rettori, Marianna Marconato ^[1] ; de Carvalho, Ana Carolina ^[1] ; Bomfim Longo, Ana Luiza ^[1] ; de Oliveira, Cleyton Zanardo ^[2] ; Kowalski, Luiz Paulo ^[3] ; Carvalho, Andre Lopes ^[4] ; Vettore, Andre Luiz ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Dept Biol Sci, BR-04039032 Sao Paulo - Brazil

^[2] Barretos Canc Hosp, Stat & Epidemiol Ctr, BR-14784400 Barretos - Brazil

^[3] AC Camargo Canc Hosp, Dept Head & Neck Surg, BR-01509010 Sao Paulo - Brazil

^[4] Barretos Canc Hosp, Dept Head & Neck Surg, BR-14784400 Barretos - Brazil

• Document type: Journal article
• Source: Carcinogenesis; v. 34, n. 1, p. 20-27, JAN 2013.
• Web of Science Citations: 26

Abstract

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 determines 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 6 months after treatment. In the analysis of salivary rinse samples taken at diagnosis of HNSCC patients, five 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 6 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 patients' subgroups with high risk of developing local recurrence. (AU)

• FAPESP's process: 05/02580-8 - Evaluation of methylation profile as prognostic marker in patients with head and neck tumors
• Grantee: Andre Luiz Vettore de Oliveira
• Support Opportunities: Regular Research Grants