title: Low VHL mRNA expression is associated with more aggressive tumor features of papillary thyroid carcinoma.
abstract: Alterations of the von Hippel-Lindau (VHL) tumor suppressor gene can cause different hereditary tumors associated with VHL syndrome, but the potential role of the VHL gene in papillary thyroid carcinoma (PTC) has not been characterized. This study set out to investigate the relationship of VHL expression level with clinicopathological features of PTC in an ethnically and geographically homogenous group of 264 patients from Serbia, for the first time. Multivariate logistic regression analysis showed a strong correlation between low level of VHL expression and advanced clinical stage (OR = 5.78, 95% CI 3.17-10.53, P<0.0001), classical papillary morphology of the tumor (OR = 2.92, 95% CI 1.33-6.44, P = 0.008) and multifocality (OR = 1.96, 95% CI 1.06-3.62, P = 0.031). In disease-free survival analysis, low VHL expression had marginal significance (P = 0.0502 by the log-rank test) but did not appear to be an independent predictor of the risk for chance of faster recurrence in a proportion hazards model. No somatic mutations or evidence of VHL downregulation via promoter hypermethylation in PTC were found. The results indicate that the decrease of VHL expression associates with tumor progression but the mechanism of downregulation remains to be elucidated.
authors.affiliation: Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan; Laboratory for Radiobiology and Molecular Genetics, "Vinca" Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia.
authors.forename: Boban
authors.initials: B
authors.lastname: Stanojevic
authors.affiliation: Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Saenko
authors.affiliation: Laboratory for Radiobiology and Molecular Genetics, "Vinca" Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia.
authors.forename: Lidija
authors.initials: L
authors.lastname: Todorovic
authors.affiliation: Laboratory for Radiobiology and Molecular Genetics, "Vinca" Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia.
authors.forename: Nina
authors.initials: N
authors.lastname: Petrovic
authors.affiliation: School of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Dragan
authors.initials: D
authors.lastname: Nikolic
authors.affiliation: School of Medicine, University of Belgrade, Belgrade, Serbia; Center for Endocrine Surgery, Clinic for Endocrinology, Clinical Center of Serbia, Belgrade, Serbia.
authors.forename: Vladan
authors.initials: V
authors.lastname: Zivaljevic
authors.affiliation: School of Medicine, University of Belgrade, Belgrade, Serbia; Center for Endocrine Surgery, Clinic for Endocrinology, Clinical Center of Serbia, Belgrade, Serbia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Paunovic
authors.affiliation: Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakashima
authors.affiliation: Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Yamashita
authors.affiliation: School of Medicine, University of Belgrade, Belgrade, Serbia; Department of Surgical Oncology, Institute of Oncology and Radiology of Serbia, Belgrade, Serbia.
authors.forename: Radan
authors.initials: R
authors.lastname: Dzodic
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000473:pathology*; D002291:Carcinoma, Papillary; D002648:Child; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012333:RNA, Messenger / Q000378:metabolism*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000473:pathology*; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human