p27 Kip1 protein expression in Hashimoto's thyroiditis.
OBJECTIVE
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.
Troncone
G
G
Dipartimento di Scienze Biomorfologiche e Funzionali, University "Federico II", 80131 Naples, Italy. gitronco@unina.it
Iaccarino
A
A
Caleo
A
A
Bifano
D
D
Pettinato
G
G
Palombini
L
L
D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000032:analysis*; D002467:Cell Nucleus / Q000737:chemistry; D056743:Cyclin D3; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000032:analysis; D004847:Epithelial Cells / Q000737:chemistry; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen / Q000032:analysis; D008214:Lymphocytes / Q000737:chemistry; D044786:S-Phase Kinase-Associated Proteins; D013961:Thyroid Gland / Q000737:chemistry* / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000276:immunology / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000032:analysis*
D015415:Biomarkers; C534696:CCND3 protein, human; D018797:Cell Cycle Proteins; D056743:Cyclin D3; D016213:Cyclins; D019394:Ki-67 Antigen; D044786:S-Phase Kinase-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27