title: Expression and prognostic value of the cell polarity PAR complex members in thyroid cancer.
abstract: Establishment and maintenance of the apical-basal cell polarity, required for proper replication, migration, specialized functions and tissue morphogenesis, relies on three evolutionary conserved complexes: PAR, CRUMBS and SCRIBBLE. Loss of cell polarity/cohesiveness (LOP/C) is implicated in cancer progression, and members of the polarity complex have been described as either oncogenes or oncosuppressors. However, no information on their role in thyroid cancer (TC) progression is available. In the present study, we evaluated the gene expression of the PAR complex members aPKCι, PARD3α/β and PARD6α/β/γ in 95 papillary TC (PTC), compared to their normal matched tissues and in 12 anaplastic TC (ATC). The mRNA and protein levels of investigated genes were altered in the majority of PTC and ATC tissues. In PTC, univariate analysis showed that reduced expression of aPKCι, PARD3β and PARD6γ mRNAs is associated with increased tumor size, and the reduced expression of PARD3β mRNA is associated also with recurrences. Multivariate analysis demonstrated that the presence of lymph node metastasis at diagnosis and the reduced expression of PARD3β are independent risk factors for recurrences, with hazard ratio, respectively, of 8.21 (p=0.006) and 3.04 (p=0.029). The latter result was confirmed by the Kaplan-Meier analysis, which evidenced the association between decreased PARD3β mRNA levels and shorter disease-free interval. In conclusion, we demonstrated that the expression of PAR complex components is deregulated in the majority of PTC and there is a general trend towards their reduction in ATC tissues. Moreover, a prognostic value for the PARD3β gene in PTCs is suggested.
authors.affiliation: Department of Experimental Medicine, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Tuccilli
authors.affiliation: Department of Surgical Sciences, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Enke
authors.initials: E
authors.lastname: Baldini
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, Rome, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Sorrenti
authors.affiliation: Department of Public Health and Infectious Diseases, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: De Vito
authors.affiliation: Department of Experimental Medicine, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: D'Armiento
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Antonelli
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Poupak
authors.initials: P
authors.lastname: Fallahi
authors.affiliation: Department of Medicine, University of Padua, Padua, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Watutantrige
authors.affiliation: Department of Surgical Sciences, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Tartaglia
authors.affiliation: Department of Medicine, University of Padua, Padua, Italy.
authors.forename: Susi
authors.initials: S
authors.lastname: Barollo
authors.affiliation: Department of Medicine, University of Padua, Padua, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Mian
authors.affiliation: Department of Surgical Sciences, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Arcieri
authors.affiliation: Department of Surgical Sciences, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Mascagni
authors.affiliation: Department of Surgical Sciences, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Pironi
authors.affiliation: Department of Surgery 'Pietro Valdoni', 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Bononi
authors.affiliation: Department of Surgical Sciences, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Vergine
authors.affiliation: Department of Surgical Sciences, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Monti
authors.affiliation: Department of Surgical Sciences, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Filippini
authors.affiliation: Department of Surgical Sciences, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Ulisse