ERG oncoprotein expression in prostate cancer: clonal progression of ERG-positive tumor cells and potential for ERG-based stratification.

ERG oncoprotein expression in prostate cancer: clonal progression of ERG-positive tumor cells and potential for ERG-based stratification.
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前列腺癌中的ERG癌蛋白表达:ERG阳性肿瘤细胞的克隆进展和基于ERG的分层的潜力。

DOI:
10.1038/pcan.2010.23
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发表时间:
2010-09
影响因子:
4.8
通讯作者:
Sesterhenn, I. A.
Sesterhenn, I. A.
中科院分区:
医学2区
文献类型:
--
作者:
Furusato, B.;Tan, S-H;Young, D.;Dobi, A.;Sun, C.;Mohamed, A. A.;Thangapazham, R.;Chen, Y.;McMaster, G.;Sreenath, T.;Petrovics, G.;McLeod, D. G.;Srivastava, S.;Sesterhenn, I. A.

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前列腺癌(CaP)中普遍存在的基因融合导致ERG原癌基因表达升高。在50-70%的前列腺肿瘤中存在的ERG激活强调了CaP中最常见的致癌性改变之一。尽管有许多关于基因融合和mRNA表达的报道,但CaP中ERG癌蛋白的状态仍有待确定。此外,ERG蛋白为基础的检测方法的发展可能提供一个新的层面,涉及不同的雄激素调节的启动子和ERG蛋白编码序列的基因融合的评估。通过对132例全标本前列腺(261个肿瘤病灶和20多万个良性腺体)ERG癌蛋白核表达的详尽评价,我们证明了使用高度特异性抗ERG单克隆抗体检测前列腺肿瘤细胞的特异性为99.9%。在随机选择的标本中,ERG癌蛋白表达与融合转录本或基因融合相关。前列腺上皮内瘤变(PIN)的ERG阳性病灶与ERG阳性癌(85个PIN切片中的82个,96.5%)的高度一致性证实了65%(132个中的86个)患者的ERG在前列腺肿瘤克隆选择中的生物学作用。相反,ERG阴性PIN与ERG阴性癌相关。总之,在个体肿瘤中检测到的均匀和强ERG表达确立了基于ERG癌蛋白的CaP分层的可能性。
Gene fusions prevalent in prostate cancer (CaP) lead to the elevated expression of the ERG proto-oncogene. ERG activation present in 50–70% of prostate tumors underscores one of the most common oncogenic alterations in CaP. Despite numerous reports of gene fusions and mRNA expression, ERG oncoprotein status in CaP still remains to be defined. Furthermore, development of ERG protein-based assays may provide a new dimension to evaluation of gene fusions involving diverse androgen-regulated promoters and the ERG protein-coding sequence. Through exhaustive evaluations of 132 whole-mount prostates (261 tumor foci and over 200 000 benign glands) for the ERG oncoprotein nuclear expression, we demonstrated 99.9% specificity for detecting prostate tumor cells using a highly specific anti-ERG monoclonal antibody. The ERG oncoprotein expression correlated well with fusion transcript or gene fusion in randomly selected specimens. Strong concordance of ERG-positive foci of prostatic intraepithelial neoplasia (PIN) with ERG-positive carcinoma (82 out of 85 sections with PIN, 96.5%) affirms the biological role of ERG in clonal selection of prostate tumors in 65% (86 out of 132) of patients. Conversely, ERG negative PINs were associated with ERG-negative carcinoma. Taken together, the homogeneous and strong ERG expression detected in individual tumors establishes the potential for ERG oncoprotein-based stratification of CaP.
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