TWIST1 promoter methylation is associated with prognosis in tonsillar squamous cell carcinoma

• Published in: Human pathology 2013-09, Vol.44 (9), p.1722-1729
• Main Authors: Kwon, Mi Jung, MD, PhD, Kwon, Ji Hyun, MD, Nam, Eun Sook, MD, PhD, Shin, Hyung Sik, MD, PhD, Lee, Dong Jin, MD, PhD, Kim, Jin Hwan, MD, PhD, Rho, Young Soo, MD, PhD, Sung, Chang Ohk, MD, Lee, Won Jae, MD, Cho, Seong Jin, MD, PhD
• Format: Article
• Language: English
• Subjects: Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - secondary; Deoxyribonucleic acid; DNA; DNA Methylation; Female; Gene Silencing; Head & neck cancer; Hospitals; Humans; Lymph Nodes - pathology; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Pathology; Polymerase chain reaction; Promoter methylation; Proteins; Republic of Korea - epidemiology; Squamous cell carcinoma; Survival Rate; Tonsil; Tonsillar Neoplasms - genetics; Tonsillar Neoplasms - metabolism; Tonsillar Neoplasms - mortality; Tonsillar Neoplasms - pathology; Tumors; Twist-Related Protein 1 - genetics; Twist-Related Protein 1 - metabolism; TWIST1
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2013.03.004

Summary Tonsillar squamous cell carcinomas (TSCC) frequently present with locally advanced diseases and cervical metastases, which are associated with poor prognoses. Epithelial-mesenchymal transition (EMT) is critical for tumor invasiveness and metastatic potential. Recent studies have shown that TWIST1 -inducing EMT is overexpressed and hypermethylated in several cancers, indicating disease progression. The aim of the present study was to determine the clinical and prognostic significance of TWIST1 hypermethylation and EMT-related protein expression in TSCC. Methylation levels of TWIST1 promoter were analyzed by quantitative real-time methylation-specific polymerase chain reaction. Immunohistochemical analyses of TWIST1, Snail, and SMAD nuclear interacting protein-1 (SNIP1) were performed in 65 formalin-fixed, paraffin-embedded blocks of surgically resected specimens. TWIST1 promoter hypermethylation was found in 27.7% (18/65) of TSCCs. TWIST1 promoter hypermethylation was associated with poor differentiation ( P = .012). Contralateral cervical lymph node metastasis was more frequently observed in TWIST1 -methylated tumors ( P = .029). High protein expressions of TWIST1, Snail, and SNIP1 were observed in 14 TSCC specimens (21.5%), 21 TSCC specimens (32.3%), and 38 TSCC specimens (58.5%), respectively. SNIP1 expression correlated significantly with TWIST1 methylation ( P = .001), whereas TWIST1 protein expression did not. Contralateral cervical lymph node metastasis was an independent risk factor of the decreased overall survival rate ( P = .002). TWIST1 methylation ( P = .031) and pN stage ( P = .037) were independent factors of poor prognoses affecting disease-free survival. TWIST1 promoter hypermethylation may be a useful molecular marker for predicting prognoses and contralateral cervical lymph node metastases in patients with TSCC.