AIMS: Hashimoto's thyroiditis (HT) is an autoimmune disease in which both proliferation and apoptosis are enhanced. p27(Kip1) protein protects tissues from disease mechanisms that involve excessive cell proliferation and apoptosis. This study investigated whether there is loss of p27(Kip1) expression in HT and whether p27(Kip1) immunoreactivity has any relation to the proliferative indicator Ki-67. Because p27(Kip1) is regulated through either degradation, mediated by the S phase kinase associated protein 2 (Skp2), or sequestration, via D3 cyclin, the expression of these proteins was also investigated. METHODS: Immunohistochemistry was used to assess p27(Kip1), Ki-67, Skp2, and cyclin D3 expression in 19 cases of HT and in 10 normal thyroids. The results were evaluated by image analysis and reported as labelling indices (LIs) in both groups. RESULTS: The p27(Kip1) LI was lower in HT than in normal thyroid (28% v 75%; p < 0.001), whereas Ki-67 (1.13% v 0.13%), Skp2 (0.74% v 0.15%), and cyclin D3 (1.56% v 0.00%) LIs were higher in HT than in normal thyroids (p < 0.001). There was no correlation between p27(Kip1) and the expression of Ki-67, Skp2, and cyclin D3. CONCLUSIONS: p27(Kip1) downregulation is not exclusive to tumours but occurs also in HT, independently of the proliferative status and of changes in Skp2 and cyclin D3 expression. Further investigation is required to understand the mechanisms leading to p27 deregulation because these observations suggest that the regulation of p27(Kip1) expression in epithelial thyroid cells may play a role in HT pathogenesis.
AIMS: Hashimoto's thyroiditis (HT) is an autoimmune disease in which both proliferation and apoptosis are enhanced. p27(Kip1) protein protects tissues from disease mechanisms that involve excessive cell proliferation and apoptosis. This study investigated whether there is loss of p27(Kip1) expression in HT and whether p27(Kip1) immunoreactivity has any relation to the proliferative indicator Ki-67. Because p27(Kip1) is regulated through either degradation, mediated by the S phase kinase associated protein 2 (Skp2), or sequestration, via D3 cyclin, the expression of these proteins was also investigated. METHODS: Immunohistochemistry was used to assess p27(Kip1), Ki-67, Skp2, and cyclin D3 expression in 19 cases of HT and in 10 normal thyroids. The results were evaluated by image analysis and reported as labelling indices (LIs) in both groups. RESULTS: The p27(Kip1) LI was lower in HT than in normal thyroid (28% v 75%; p < 0.001), whereas Ki-67 (1.13% v 0.13%), Skp2 (0.74% v 0.15%), and cyclin D3 (1.56% v 0.00%) LIs were higher in HT than in normal thyroids (p < 0.001). There was no correlation between p27(Kip1) and the expression of Ki-67, Skp2, and cyclin D3. CONCLUSIONS:p27(Kip1) downregulation is not exclusive to tumours but occurs also in HT, independently of the proliferative status and of changes in Skp2 and cyclin D3 expression. Further investigation is required to understand the mechanisms leading to p27 deregulation because these observations suggest that the regulation of p27(Kip1) expression in epithelial thyroid cells may play a role in HT pathogenesis.
Authors: M Sánchez-Beato; F I Camacho; J C Martínez-Montero; A I Sáez; R Villuendas; L Sánchez-Verde; J F García; M A Piris Journal: Blood Date: 1999-07-15 Impact factor: 22.113
Authors: M Gstaiger; R Jordan; M Lim; C Catzavelos; J Mestan; J Slingerland; W Krek Journal: Proc Natl Acad Sci U S A Date: 2001-04-17 Impact factor: 11.205
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Authors: G Baldassarre; B Belletti; P Bruni; A Boccia; F Trapasso; F Pentimalli; M V Barone; G Chiappetta; M T Vento; S Spiezia; A Fusco; G Viglietto Journal: J Clin Invest Date: 1999-10 Impact factor: 14.808
Authors: C Doglioni; C Chiarelli; E Macrí; A P Dei Tos; E Meggiolaro; P Dalla Palma; M Barbareschi Journal: J Pathol Date: 1998-06 Impact factor: 7.996
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Authors: P Pallante; M T Berlingieri; G Troncone; M Kruhoffer; T F Orntoft; G Viglietto; A Caleo; I Migliaccio; M Decaussin-Petrucci; M Santoro; L Palombini; A Fusco Journal: Br J Cancer Date: 2005-08-22 Impact factor: 7.640