DNA hypermethylation markers of poor outcome in laryngeal cancer

被引:24
作者
Stephen, Josena K. [1 ]
Chen, Kang Mei [1 ]
Shah, Veena [2 ]
Havard, Shaleta [1 ]
Kapke, Alissa [3 ]
Lu, Mei [3 ]
Benninger, Michael S. [4 ]
Worsham, Maria J. [1 ]
机构
[1] Henry Ford Hosp, Dept Otolaryngol Head & Neck Surg, 1 Ford Pl,1D, Detroit, MI 48202 USA
[2] Henry Ford Hosp, Dept Pathol, Detroit, MI 48202 USA
[3] Henry Ford Hosp, Dept Biostat & Res Epidemiol, Detroit, MI 48202 USA
[4] Cleveland Clin, Head & Neck Inst, Cleveland, OH 44195 USA
关键词
Laryngeal cancer; Hypermethylation; ESR1; HIC1; TUMOR-SUPPRESSOR GENE; SQUAMOUS-CELL CARCINOMA; PROMOTER HYPERMETHYLATION; ESTROGEN-RECEPTOR; CPG ISLAND; DISEASE PROGRESSION; EPIGENETIC EVENTS; FREQUENT EVENT; MULTIPLE GENES; PRIMARY HEAD;
D O I
10.1007/s13148-010-0005-3
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
This study examined molecular (DNA hyper-methylation), clinical, histopathological, demographical, smoking, and alcohol variables to assess diagnosis (early versus late stage) and prognosis (survival) outcomes in a retrospective primary laryngeal squamous cell carcinoma (LSCC) cohort. The study cohort of 79 primary LSCC was drawn from a multi-ethnic (37% African American), primary care patient population, diagnosed by surgical biopsies in the Henry Ford Health System from 1991 to 2004 and followed from 5 to 18 years (through 2009). Of the 41 variables, univariate risk factors of p<0.10 were tested in multivariate models (logistic regression (diagnosis) and Cox (survival) models (p<0.05)). Aberrant methylation of estrogen receptor 1 (ESR1; p=0.01), race as African American (p=0.04), and tumor necrosis extensive; p=0.02) were independent predictors of late stage LSCC. Independent predictors of poor survival included presence of vascular invasion (p=0.0009), late stage disease (p=0.03), and methylation of the hyper-methylated in cancer 1 (HIC1) gene (p=0.0002). Aberrant methylation of ESR1 and HIC1 signified independent markers of poorer outcome. In this multi-ethnic, primary LSCC cohort, race remained a predictor of late stage disease supporting disparate diagnosis outcomes for African American patients with LSCC.
引用
收藏
页码:61 / 69
页数:9
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