The role of cell cycle regulatory protein, cyclin D1, in the progression of thyroid cancer
The role of cell cycle regulatory protein, cyclin D1, in the progression of thyroid cancer
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DOI：
10.1038/modpathol.3880157
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发表时间：
2000-08-01
期刊：
影响因子：
7.5
通讯作者：
Khan, A
中科院分区：
文献类型：
--
作者：
Wang, S;Lloyd, RV;Khan, A
细胞周期蛋白依赖性激酶促进细胞周期进程，其被细胞周期蛋白（包括细胞周期蛋白D1）激活，并被细胞周期蛋白依赖性激酶抑制剂（CDKI）（如p27）灭活。我们以前的研究表明，甲状腺乳头状癌和更具侵袭性的甲状腺癌中p27的表达与甲状腺腺瘤相比降低，甲状腺腺瘤和乳头状癌之间的细胞周期蛋白D1表达水平几乎相似。这些结果表明，CDKIs可能在甲状腺癌的发生中起重要作用，并且它们可能在甲状腺癌的恶性进展中起有限的作用。细胞周期蛋白D1在甲状腺癌恶性进展中的作用尚未确定。我们研究了34例常规乳头状癌（CPC），10例微创滤泡癌（MIFC），和32例更具侵略性的甲状腺癌（ATC），其中包括11个高细胞变异，乳头状癌的柱状细胞变异，7个岛状癌，和13个未分化癌细胞周期蛋白D1的表达免疫组化。细胞周期蛋白D1染色按染色评分分为0，阴性; 1+，小于25%; 2+，25 - 50%;和3+，超过50%的肿瘤细胞染色阳性。Kruskal-Wallis单因素方差分析和Wilcoxon秩和/Mann-Whitney U检验用于评估研究组之间细胞周期蛋白D1表达的差异。34例CPC中28例为cyclin D1阳性，24例（70%）为1+，3例（9%）为2+，1例（3%）为3+。10个MIFCs中有7个细胞周期蛋白D1阳性，5个（71%）为1+，其余2个（29%）为2+。另一方面，32个ATC中有28个显示cyclin D1免疫染色。其中，3例（9%）为1+，5例（13%）为2+，20例（63%）为3+阳性。本研究表明，与CPC（P <0.001）和MIFC（P <0.005）相比，ATC中cyclin D1显著过表达，表明cyclin D1表达可能在肿瘤进展中起作用，并可能在甲状腺癌中具有预后意义。
Cell cycle progression is facilitated by cyclin-dependent kinases that are activated by cyclins including cyclin D1 and inactivated by cyclin-dependent kinase inhibitors (CDKIs) such as p27. Our previous studies have demonstrated decreased p27 expression in both papillary and more aggressive carcinomas of the thyroid compared to thyroid adenoma and almost similar level of cyclin D1 expression between thyroid adenoma and papillary carcinoma. These results indicate that CDKIs may have an important role In the carcinogenesis of the thyroid and that they probably have a limited role in malignant progression of the thyroid cancer. The role of cyclin D1 in malignant progression of thyroid carcinoma has yet to be established. We studied the expression of cyclin D1 by immunohistochemistry in 34 cases of conventional papillary carcinoma (CPC), 10 cases of minimally invasive follicular carcinoma (MIFC), and 32 cases of more aggressive thyroid carcinoma (ATC), which included 11 tall cell variants, one columnar cell variant of papillary carcinoma, seven insular carcinomas, and 13 anaplastic carcinomas. Cyclin D1 staining was classified by staining score as 0, negative; 1+, less than 25%; 2+, 25 to 50%; and 3+, more than 50% tumor cells staining positive. Kruskal-Wallis one-way ANOVA and Wilcoxon Rank Sum/Mann-Whitney U Test was used to assess the difference In the expression of cyclin D1 between the study groups. Twenty-eight out of the 34 CPCs were cyclin D1 positive, 24 (70%) were 1+, 3 (9%) were 2+, and one (3%) were 3+ positive. Seven of 10 MIFCs were cyclin D1 positive, five (71%) were 1+, and the remaining two (29%) were 2+ positive. On the other hand, 28 of 32 ATCs showed cyclin D1 immunostaining. Of these, three (9%) were 1+, five (13%) were 2+, and 20 (63%) were 3+ positive. This study demonstrates a significant overexpression of cyclin D1 in ATC compared CPC (P < .001) and MIFC (P < .005), suggesting that the cyclin D1 expression may play a role in tumor progression and may have prognostic significance in thyroid cancer.