Cyclin D1 overexpression in thyroid papillary microcarcinoma: its association with tumour size and aberrant beta-catenin expression.
OBJECTIVE
Cyclin D1 is a target molecule transcriptionally activated by aberrant beta-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.


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 beta-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 beta-catenin expression.


CONCLUSIONS
Cyclin D1 overexpression and correlation with aberrant beta-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/beta-catenin pathway.
Lantsov
D
D
Medical Radiological Research Centre, Russian Academy of Medical Sciences, Obninsk, Russian Federation.
Meirmanov
S
S
Nakashima
M
M
Kondo
H
H
Saenko
V
V
Naruke
Y
Y
Namba
H
H
Ito
M
M
Abrosimov
A
A
Lushnikov
E
E
Sekine
I
I
Yamashita
Sh
Sh
D000328:Adult; D002291:Carcinoma, Papillary / Q000378:metabolism / Q000473:pathology*; D019938:Cyclin D1 / Q000096:biosynthesis*; D003598:Cytoskeletal Proteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008207:Lymphatic Metastasis; D008875:Middle Aged; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology*; D015534:Trans-Activators / Q000096:biosynthesis*; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D019394:Ki-67 Antigen; D015534:Trans-Activators; D051176:beta Catenin; D019938:Cyclin D1