title: TWIST1 promoter methylation is associated with prognosis in tonsillar squamous cell carcinoma.
abstract: 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.
authors.affiliation: Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Gyeonggi-do, 431-070, Republic of Korea.
authors.forename: Mi Jung
authors.initials: MJ
authors.lastname: Kwon
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Kwon
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Nam
authors.forename: Hyung Sik
authors.initials: HS
authors.lastname: Shin
authors.forename: Dong Jin
authors.initials: DJ
authors.lastname: Lee
authors.forename: Jin Hwan
authors.initials: JH
authors.lastname: Kim
authors.forename: Young Soo
authors.initials: YS
authors.lastname: Rho
authors.forename: Chang Ohk
authors.initials: CO
authors.lastname: Sung
authors.forename: Won Jae
authors.initials: WJ
authors.lastname: Lee
authors.forename: Seong Jin
authors.initials: SJ
authors.lastname: Cho
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D019175:DNA Methylation; D005260:Female; D020868:Gene Silencing; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D056910:Republic of Korea / Q000453:epidemiology; D015996:Survival Rate; D014067:Tonsillar Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D051879:Twist-Related Protein 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1
keywords: Promoter methylation; Squamous cell carcinoma; TWIST1; Tonsil