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胰岛素样生长因子受体 1(IGF1R)基因拷贝数与可手术非小细胞肺癌的生存相关:IGF1R 荧光原位杂交、蛋白表达和 mRNA 表达的比较。

Insulin-like growth factor receptor 1 (IGF1R) gene copy number is associated with survival in operable non-small-cell lung cancer: a comparison between IGF1R fluorescent in situ hybridization, protein expression, and mRNA expression.

机构信息

University of Colorado Cancer Center, PO Box 6511, Mail Stop 8111, Aurora, CO 80045, USA.

出版信息

J Clin Oncol. 2010 May 1;28(13):2174-80. doi: 10.1200/JCO.2009.24.6611. Epub 2010 Mar 29.

Abstract

PURPOSE

The purpose of this study was to characterize insulin-like growth factor-1 receptor (IGF1R) protein expression, mRNA expression, and gene copy number in surgically resected non-small-cell lung cancers (NSCLC) in relation to epidermal growth factor receptor (EGFR) protein expression, patient characteristics, and prognosis.

PATIENTS AND METHODS

One hundred eighty-nine patients with NSCLC who underwent curative pulmonary resection were studied (median follow-up, 5.3 years). IGF1R protein expression was evaluated by immunohistochemistry (IHC) with two anti-IGF1R antibodies (n = 179). EGFR protein expression was assessed with PharmDx kit. IGF1R gene expression was evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) from 114 corresponding fresh-frozen samples. IGF1R gene copy number was assessed by fluorescent in situ hybridization using customized probes (n = 181).

RESULTS

IGF1R IHC score was higher in squamous cell carcinomas versus other histologies (P < .001) and associated with stage (P = .03) but not survival (P = .46). IGF1R and EGFR protein expression showed significant correlation (r = 0.30; P < .001). IGF1R gene expression by qRT-PCR was higher in squamous cell versus other histologies (P = .006) and did not associate with other clinical features nor survival (P = .73). Employing criteria previously established for EGFR copy number, patients with IGF1R amplification/high polysomy (n = 48; 27%) had 3-year survival of 58%, patients with low polysomy (n = 87; 48%) had 3-year survival of 47% and patients with trisomy/disomy (n = 46; 25%) had 3-year survival of 35%, respectively (P = .024). Prognostic value of high IGF1R gene copy number was confirmed in multivariate analysis.

CONCLUSION

IGF1R protein expression is higher in squamous cell versus other histologies and correlates with EGFR expression. IGF1R protein and gene expression does not associate with survival, whereas high IGF1R gene copy number harbors positive prognostic value.

摘要

目的

本研究旨在分析胰岛素样生长因子-1 受体(IGF1R)蛋白、mRNA 表达及基因拷贝数在手术切除的非小细胞肺癌(NSCLC)中的特征,并探讨其与表皮生长因子受体(EGFR)蛋白表达、患者特征及预后的关系。

方法

本研究共纳入 189 例行根治性肺切除术的 NSCLC 患者(中位随访时间 5.3 年)。采用两种抗 IGF1R 抗体进行免疫组化(IHC)检测 IGF1R 蛋白表达(n=179)。采用 PharmDx 试剂盒评估 EGFR 蛋白表达。114 例新鲜冷冻组织标本采用实时定量逆转录聚合酶链反应(qRT-PCR)检测 IGF1R 基因表达。181 例组织标本采用定制探针进行 IGF1R 基因拷贝数的荧光原位杂交检测。

结果

与其他组织学类型相比,鳞状细胞癌的 IGF1R IHC 评分更高(P<0.001),且与分期(P=0.03)相关,但与生存无关(P=0.46)。IGF1R 和 EGFR 蛋白表达呈显著正相关(r=0.30;P<0.001)。qRT-PCR 检测结果显示,与其他组织学类型相比,鳞状细胞癌中 IGF1R 基因表达更高(P=0.006),但与其他临床特征及生存无关(P=0.73)。采用先前建立的 EGFR 拷贝数标准,发现 IGF1R 扩增/高多倍体(n=48;27%)患者的 3 年生存率为 58%,低多倍体(n=87;48%)患者的 3 年生存率为 47%,三体/二倍体(n=46;25%)患者的 3 年生存率为 35%(P=0.024)。多因素分析结果证实高 IGF1R 基因拷贝数具有预后价值。

结论

与其他组织学类型相比,鳞状细胞癌中 IGF1R 蛋白表达更高,且与 EGFR 表达相关。IGF1R 蛋白和基因表达与生存无关,而高 IGF1R 基因拷贝数具有良好的预后价值。

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