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p27基因CDKN1B的V109G多态性表明淋巴结阴性乳腺癌患者的预后较差。

The V109G polymorphism of the p27 gene CDKN1B indicates a worse outcome in node-negative breast cancer patients.

作者信息

Schöndorf Thomas, Eisele Lewin, Göhring Uwe-Jochen, Valter Markus M, Warm Mathias, Mallmann Peter, Becker Martina, Fechteler Roland, Weisshaar Maria-Paz, Hoopmann Markus

机构信息

Department of Natural Sciences, University of Applied Sciences Bonn-Rhein-Sieg, DE-53359 Rheinbach, Germany.

出版信息

Tumour Biol. 2004 Sep-Dec;25(5-6):306-12. doi: 10.1159/000081396.

Abstract

Although p27 plays a central role in cell cycle regulation, its role in breast cancer prognosis is controversial. Furthermore, the p27 gene CDKN1B carries a polymorphism with unknown functional relevance. This study was designed to evaluate p27 expression and p27 genotyping with respect to early breast cancer prognosis. 279 patients with infiltrating metastasis-free breast cancer were included in this study. p27 expression was determined in tumor tissue specimens from 261 patients by immunohistochemistry. From 108 patients, the CDKN1B genotype was examined by PCR and subsequent direct sequencing. 55.2% of the tumors were considered p27 positive. p27 expression did not correlate with any of the established parameters except for nodal involvement but significantly correlated to prolonged disease-free survival. In 35% of the tumors analyzed, the CDKN1B gene showed a polymorphism at codon 109 (V109G). The V109G polymorphism correlated with greater nodal involvement. In the node-negative subgroup, V109G correlated significantly with a shortened disease-free survival. In conclusion, the determination of the CDKN1B genotype might be a powerful tool for the prognosis of patients with early breast cancer.

摘要

尽管p27在细胞周期调控中发挥核心作用,但其在乳腺癌预后中的作用仍存在争议。此外,p27基因CDKN1B存在一种功能相关性未知的多态性。本研究旨在评估p27表达及p27基因分型与早期乳腺癌预后的关系。本研究纳入了279例无浸润转移的乳腺癌患者。通过免疫组织化学法测定了261例患者肿瘤组织标本中的p27表达。对108例患者通过聚合酶链反应(PCR)及后续直接测序检测CDKN1B基因型。55.2%的肿瘤被认为p27阳性。除淋巴结受累外,p27表达与任何既定参数均无相关性,但与无病生存期延长显著相关。在35%的分析肿瘤中,CDKN1B基因在第109密码子处出现多态性(V109G)。V109G多态性与更多的淋巴结受累相关。在淋巴结阴性亚组中,V109G与无病生存期缩短显著相关。总之,CDKN1B基因型的测定可能是早期乳腺癌患者预后评估的有力工具。

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