title: Follicular variant of papillary thyroid carcinoma: genome-wide appraisal of a controversial entity.
abstract: The majority of thyroid tumors are classified as papillary (papillary thyroid carcinomas; PTCs) or follicular neoplasms (follicular thyroid adenomas and carcinomas; FTA/FTC) based on nuclear features and the cellular growth pattern. However, classification of the follicular variant of papillary thyroid carcinoma (FVPTC) remains an issue of debate. These tumors contain a predominantly follicular growth pattern but display nuclear features and overall clinical behavior consistent with PTC. In this study, we used comparative genomic hybridization (CGH) to compare the global chromosomal aberrations in FVPTC to the PTC of classical variant (classical PTC) and FTA/FTC. In addition, we assessed the presence of peroxisome proliferator-activated receptor-gamma (PPARG) alteration, a genetic event specific to FTA/FTC, using Southern blot and immunohistochemistry analyses. In sharp contrast to the findings in classical PTC (4% of cases), CGH analysis demonstrated that both FVPTC (59% of cases) and FTA/FTC (36% of cases) were commonly characterized by aneuploidy (P = 0.0002). Moreover, the pattern of chromosomal aberrations (gains at chromosome arms 2q, 4q, 5q, 6q, 8q, and 13q and deletions at 1p, 9q, 16q, 17q, 19q, and 22q) in the follicular variant of PTC closely resembled that of FTA/FTC. Aberrations in PPARG were uniquely detected in FVPTC and FTA/FTC. Our findings suggest a stronger relationship between the FVPTC and FTA/FTC than previously appreciated and support further consideration of the current classification of thyroid neoplasms.
authors.affiliation: Laboratory of Epithelial Cancer Biology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: Volkert B
authors.initials: VB
authors.lastname: Wreesmann
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Ghossein
authors.forename: Michael
authors.initials: M
authors.lastname: Hezel
authors.forename: Debenranrath
authors.initials: D
authors.lastname: Banerjee
authors.forename: Ashok R
authors.initials: AR
authors.lastname: Shaha
authors.forename: R Michael
authors.initials: RM
authors.lastname: Tuttle
authors.forename: Jatin P
authors.initials: JP
authors.lastname: Shah
authors.forename: Pulivarthi H
authors.initials: PH
authors.lastname: Rao
authors.forename: Bhuvanesh
authors.initials: B
authors.lastname: Singh
mesh_terms: D000328:Adult; D000368:Aged; D000782:Aneuploidy; D002291:Carcinoma, Papillary / Q000145:classification* / Q000235:genetics; D018265:Carcinoma, Papillary, Follicular / Q000145:classification* / Q000235:genetics; D002869:Chromosome Aberrations / Q000706:statistics & numerical data; D002872:Chromosome Deletion; D020732:Cytogenetic Analysis / Q000379:methods / Q000706:statistics & numerical data; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005784:Gene Amplification / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization / Q000379:methods; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm