title: Methylation Markers for Early Detection and Differentiation of Follicular Thyroid Cancer Subtypes.
abstract: Thyroid cancer has the fastest rising incidence rates and is the fifth most common cancer in women. There are four main types of which the papillary and follicular types together account for >90%, followed by medullary cancers (3%-5%) and anaplastic carcinomas (<3%). For individuals who present with early stage disease of papillary and follicular cancers, there are no accurate markers to predict whether they will develop metastatic or recurrent disease. Our immediate goal is to molecularly differentiate follicular cancer subtypes for enhanced classification. Promoter methylation status of genes with reported associations in thyroid cancer (CASP8, CDKN2A, DAPK1, ESR1, NIS, RASSF1andTIMP3) were examined in a cohort of follicular thyroid cancers comprising of 26 Hurthle and 27 Classic subtypes utilizing quantitative methylation-specific PCR.RASSF1was differentially methylated in Classic tumor tissue compared to Hurthle (p<0.001). Methylation ofRASSF1pointed to racial group differences between African Americans and Caucasian Americans (p=0.05). Extra thyroidal extension was found to be associated withDAPK1(p=0.014) andESR1(p=0.036) methylation. Late stage disease was associated with older age (p<0.001) and methylation ofDAPK1(p=0.034) andESR1(p=0.035). The methylation status ofRASSF1, DAPK1andESR1suggests the utility of methylation markers to molecularly differentiate thyroid cancer subtypes for enhanced classification and early detection of thyroid cancer.
authors.affiliation: Department of Otolaryngology/Head and Neck Research, Henry Ford Hospital, Detroit, Michigan 48202, USA.
authors.forename: Josena K
authors.initials: JK
authors.lastname: Stephen
authors.affiliation: Department of Otolaryngology/Head and Neck Research, Henry Ford Hospital, Detroit, Michigan 48202, USA.
authors.forename: Kang Mei
authors.initials: KM
authors.lastname: Chen
authors.affiliation: Department of Otolaryngology/Head and Neck Research, Henry Ford Hospital, Detroit, Michigan 48202, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Merritt
authors.affiliation: Department of Pathology, Henry Ford Hospital, Detroit, Michigan 48202, USA.
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Chitale
authors.affiliation: Department of Public Health Sciences, Henry Ford Hospital, Detroit, Michigan 48202USA.
authors.forename: George
authors.initials: G
authors.lastname: Divine
authors.affiliation: Department of Otolaryngology/Head and Neck Research, Henry Ford Hospital, Detroit, Michigan 48202, USA.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Worsham
keywords: DNA methylation; Hurthle cell cancer; QMSP; follicular thyroid cancer