Molecular alterations of EGFR and PTEN in prostate cancer: association with high-grade and advanced-stage carcinomas
Molecular alterations of EGFR and PTEN in prostate cancer: association with high-grade and advanced-stage carcinomas
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DOI：
10.1038/modpathol.2010.45
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发表时间：
2010-05-01
期刊：
影响因子：
7.5
通讯作者：
Lloreta, Josep
中科院分区：
文献类型：
--
作者：
de Muga, Silvia;Hernandez, Silvia;Lloreta, Josep
前列腺癌是西方世界男性癌症相关死亡的第二大原因。EGFR和PTEN的联合改变在前列腺癌中的潜在预后作用还没有很好地确定。本研究的目的是调查这一作用。EGFR和PTEN体细胞突变的患病率，EGFR扩增和EGFR蛋白表达在一系列前列腺癌中进行了研究，根据目前的Gleason分级系统进行分类。突变分析显示，分别在98例（8%）和92例（3%）前列腺癌中有8例EGFR和3例PTEN突变。EGFR-PTEN突变的合并患病率为11%。EGFR过表达存在于31%的腺癌中，Gleason分级= 8和转移性腺癌之间存在轻微显著差异（P = 0.068）。4例病例（4/31; 13%）因7号染色体多体性而获得EGFR基因。在35%的腺癌中，我们发现了某种类型的EGFR-PTEN改变，其倾向于与晚期前列腺癌相关（P = 0.04）。IVS 18 +19多态性也与更晚期的前列腺癌相关。这是第一个研究报告突变的EGFR和PTEN在同一系列的前列腺癌。蛋白质过表达是最常见的EGFR异常。EGFR和PTEN基因突变是次要事件，尽管前列腺癌代表EGFR基因突变更普遍的第三种肿瘤。EGFR-PTEN信号通路的改变存在于三分之一的前列腺癌中，特别是影响更晚期的病例。现代病理学（2010）23，703-712; doi：10.1038/modpathol.2010.45;在线发表2010年3月5日
Prostate cancer is the second cause of cancer-related death in men of the Western world. The potential prognostic role of the combined alterations in EGFR and PTEN in prostate cancer is not well established. It was the aim of the study to investigate this role. Prevalence of EGFR and PTEN somatic mutations, EGFR amplification and EGFR protein expression were investigated in a series of prostate adenocarcinomas, classified according to the current Gleason grading system. Mutational analysis revealed eight EGFR and three PTEN mutations in 98 (8%) and 92 (3%) prostate adenocarcinomas, respectively. The combined prevalence of EGFR-PTEN mutations was 11%. EGFR overexpression was present in 31% of adenocarcinomas, with a marginally significant difference (P = 0.068) between Gleason grade = 8 and metastatic adenocarcinomas. Four cases (4 of 31; 13%) had an EGFR gene gain due to chromosome 7 polysomy. In 35% of adenocarcinomas we found some type of EGFR-PTEN alteration, with a tendency to be associated with advanced-stage prostate adenocarcinomas (P = 0.04). The IVS18+19 polymorphism was also associated with more advanced prostate adenocarcinomas. This is the first study reporting mutations of EGFR and PTEN in the same series of prostate adenocarcinomas. Protein overexpression is the most frequent EGFR abnormality. Mutations in EGFR and PTEN genes are a minor event, although prostate cancer represents the third neoplasm in which the EGFR gene mutations are more prevalent. Alterations in the EGFR-PTEN signaling pathway are present in a third of prostate adenocarcinomas, particularly affecting the more advanced cases. Modern Pathology (2010) 23, 703-712; doi: 10.1038/modpathol.2010.45; published online 5 March 2010