title: Deregulated expression of VHL mRNA variants in papillary thyroid cancer.
abstract: Recent findings demonstrated that a subset of papillary thyroid cancers (PTCs) is characterized by reduced expression of the von Hippel-Lindau (VHL) tumor suppressor gene, and that lowest levels associated with more aggressive PTCs. In the present study, the levels of the two VHL mRNA splicing variants, VHL-213 (V1) and VHL-172 (V2), were measured in a series of 96 PTC and corresponding normal matched tissues by means of quantitative RT-PCR. Variations in the mRNA levels were correlated with patients' clinicopathological parameters and disease-free interval (DFI). The analysis of VHL mRNA in tumor tissues, compared to normal matched tissues, revealed that its expression was either up- or down-regulated in the majority of PTC. In particular, V1 and V2 mRNA levels were altered, respectively, in 78 (81.3%) and 65 (67.7%) out of the 96 PTCs analyzed. A significant positive correlation between the two mRNA variants was observed (p < 0.001). Univariate analysis documented the lack of association between each variant and clinicopathological parameters such as age, tumor size, histology, TNM stage, lymph node metastases, and BRAF mutational status. However, a strong correlation was found between altered V1 or V2 mRNA levels and DFI. Multivariate regression analysis indicated higher V1 mRNA values, along with lymph node metastases at diagnosis, as independent prognostic factors predicting DFI. In conclusion, the data reported demonstrate that VHL gene expression is deregulated in the majority of PTC tissues. Of particular interest is the apparent protective role exerted by VHL transcripts against PTC recurrences.
authors.affiliation: Department of Surgical Sciences, "Sapienza" University of Rome, Italy.
authors.forename: Enke
authors.initials: E
authors.lastname: Baldini
authors.affiliation: Department of Experimental Medicine, "Sapienza" University of Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Tuccilli
authors.affiliation: CNRS-UMR 6290 (IGDR) Université Rennes 1, Rennes, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Arlot-Bonnemains
authors.affiliation: CNRS-UMR 6290 (IGDR) Université Rennes 1, Rennes, France.
authors.forename: Frank
authors.initials: F
authors.lastname: Chesnel
authors.affiliation: Department of Surgical Sciences, "Sapienza" University of Rome, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Sorrenti
authors.affiliation: Department of Public Health and Infectious Diseases, "Sapienza" University of Rome, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: De Vito
authors.affiliation: Department of Surgical Sciences, "Sapienza" University of Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Catania
authors.affiliation: Department of Experimental Medicine, "Sapienza" University of Rome, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: D'Armiento
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Antonelli
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Italy.
authors.forename: Poupak
authors.initials: P
authors.lastname: Fallahi
authors.affiliation: Department of Medicine, University of Padua, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Watutantrige-Fernando
authors.affiliation: Department of Surgical Sciences, "Sapienza" University of Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Tartaglia
authors.affiliation: Department of Medicine, University of Padua, Italy.
authors.forename: Susi
authors.initials: S
authors.lastname: Barollo
authors.affiliation: Department of Medicine, University of Padua, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Mian
authors.affiliation: Department of Surgery "Pietro Valdoni", "Sapienza" University of Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Bononi
authors.affiliation: Department of Surgical Sciences, "Sapienza" University of Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Arceri
authors.affiliation: Department of Surgical Sciences, "Sapienza" University of Rome, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Mascagni
authors.affiliation: Department of Surgical Sciences, "Sapienza" University of Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Vergine
authors.affiliation: Department of Surgical Sciences, "Sapienza" University of Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Pironi
authors.affiliation: Department of Surgical Sciences, "Sapienza" University of Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Monti
authors.affiliation: Department of Surgical Sciences, "Sapienza" University of Rome, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Filippini
authors.affiliation: Department of Surgical Sciences, "Sapienza" University of Rome, Italy. Electronic address: salvatore.ulisse@uniroma1.it.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Ulisse
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing / Q000235:genetics*; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C497446:VHL protein, human
keywords: Biomarkers; Gene expression; Papillary thyroid cancer; Prognosis; VHL