© 2003 BMJ Publishing Group Ltd. & Association of Clinical Pathologists
ORIGINAL ARTICLE
p27Kip1 protein expression in Hashimotos thyroiditis
Dipartimento di Scienze Biomorfologiche e Funzionali, University "Federico II", 80131 Naples, Italy
Correspondence to:
Correspondence to:
Dr G Troncone, Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli Federico II, Via S. Pansini 5, 80131 Napoli, Italia;
gitronco{at}unina.it
Aims: Hashimotos thyroiditis (HT) is an autoimmune disease in which both proliferation and apoptosis are enhanced. p27Kip1 protein protects tissues from disease mechanisms that involve excessive cell proliferation and apoptosis. This study investigated whether there is loss of p27Kip1 expression in HT and whether p27Kip1 immunoreactivity has any relation to the proliferative indicator Ki-67. Because p27Kip1 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 p27Kip1, 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 p27Kip1 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 p27Kip1 and the expression of Ki-67, Skp2, and cyclin D3.
Conclusions: p27Kip1 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 p27Kip1 expression in epithelial thyroid cells may play a role in HT pathogenesis.
Keywords: thyroid; Hashimotos thyroiditis; p27Kip1; Ki-67; Skp2; cyclin D3
Abbreviations: HT, Hashimotos thyroiditis; IL, interleukin; LI, labelling index; Skp2, S phase kinase associated protein 2
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