Cyclin D1 overexpression in thyroid papillary microcarcinoma: its association with tumour size and aberrant β‐catenin expression

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Abstract
Aims : Cyclin D1 is a target molecule transcriptionally activated by aberrant β‐catenin in Wnt signalling. Thyroid papillary microcarcinoma (PMC) may be considered a precursor of papillary thyroid cancer (PTC). Ki67 is widely used as a proliferation marker. The aim of this study was to determine whether cyclin D1 overexpression is involved in early thyroid carcinogenesis.Methods and results : Thirty‐five cases of PMC were examined immunohistochemically, including 11 cases less than 5 mm (PMC < 5) and 24 cases more than 5 mm (PMC > 5), and 18 PTC cases (size 11–15 mm). Cyclin D1 expression was significantly lower in PMC < 5 than in PMC > 5, while there was no significant difference between PMC > 5 and PTC. Statistical analysis revealed significant correlations between cyclin D1 labelling index (LI) and Ki67 LI (P = 0.0272)/cytoplasmic β‐catenin expression (P < 0.001) in PMC and PTC. Four of five PMC > 5 cases with lymph node (LN) metastases displayed a high cyclin D1 LI and strong cytoplasmic β‐catenin expression.Conclusions : Cyclin D1 overexpression and correlation with aberrant β‐catenin expression were demonstrated in PMC. Cyclin D1 expression was significantly associated with tumour size and LN metastases in PMC. Cyclin D1 may be up‐regulated at an early stage of thyroid carcinogenesis and promote tumour growth and metastatic potency in PMC through activation of the Wnt/β‐catenin pathway.