细胞周期/凋亡基因在甲状腺癌进展谱系中的表达模式。

Patterns of expression of cell cycle/apoptosis genes along the spectrum of thyroid carcinoma progression.

作者信息

Saltman Benjamin, Singh Bhuvanesh, Hedvat Cyrus V, Wreesmann Volkert B, Ghossein Ronald

机构信息

Department of Otolaryngology, Columbia University College of Physicians and Surgeons, New York, NY 10021, USA.

出版信息

Surgery. 2006 Dec;140(6):899-905; discussion 905-6. doi: 10.1016/j.surg.2006.07.027.

DOI:10.1016/j.surg.2006.07.027

PMID:17188136

Abstract

BACKGROUND

Genetic screening studies suggest that genetic changes underlie progression from well differentiated to anaplastic thyroid cancers. The aim of this study is to determine to what extent cell cycle/apoptosis regulators contribute to cancer progression.

METHODS

Tissue microarrarys (TMAs) were constructed from well-differentiated papillary thyroid carcinoma (WDPTC; n = 41), poorly differentiated thyroid carcinoma (PDTC; n = 43), and anaplastic thyroid carcinoma (ATC; n = 22). TMAs were immunostained for 7 different cell cycle/apoptosis-related genes (p53, Ki-67, bcl-2, mdm-2, cyclin D1, p21, and p27).

RESULTS

p53 (0%, 12%, 32%) and Ki-67 (5%, 49%, 82%) were expressed with increasing frequency, and bcl-2 (68%, 42%, 0%) and p21 (40%, 7%, 0%) with decreasing frequency in WDPTC to PDTC and ATC, respectively (P < .001). Interestingly, mdm-2 (54%, 5%, 0%) showed decreased expression along the progression axis (P < .001). p27 and cyclin D1 were expressed in <15% of cases, with a trend toward decreasing expression from WDPTC to PDTC to ATC.

CONCLUSIONS

These data confirm the presence of increasing genetic complexity with progressive dedifferentiation in thyroid cancer, with aberrant tumor suppressor activity and increased proliferative activity being most prevalent in ATC. The data also confirm the intermediate position of PDTC in the classification scheme of thyroid carcinomas.

摘要

背景

基因筛查研究表明，基因变化是甲状腺癌从高分化向间变性进展的基础。本研究的目的是确定细胞周期/凋亡调节因子在多大程度上促进癌症进展。

方法

组织微阵列（TMA）由高分化乳头状甲状腺癌（WDPTC；n = 41）、低分化甲状腺癌（PDTC；n = 43）和间变性甲状腺癌（ATC；n = 22）构建而成。TMA对7种不同的细胞周期/凋亡相关基因（p53、Ki-67、bcl-2、mdm-2、细胞周期蛋白D1、p21和p27）进行免疫染色。

结果

p53（0%、12%、32%）和Ki-67（5%、49%、82%）的表达频率在WDPTC至PDTC和ATC中分别呈增加趋势，而bcl-2（68%、42%、0%）和p21（40%、7%、0%）的表达频率呈下降趋势（P <.001）。有趣的是，mdm-2（54%、5%、0%）沿进展轴表达降低（P <.001）。p27和细胞周期蛋白D1在<15%的病例中表达，从WDPTC到PDTC再到ATC有表达降低的趋势。