ERG rearrangement metastasis patterns in locally advanced prostate cancer.
ERG rearrangement metastasis patterns in locally advanced prostate cancer.
复制标题
DOI：
10.1016/j.urology.2009.10.010
复制
发表时间：
2010-04
期刊：
影响因子：
2.1
通讯作者：
Rubin MA
中科院分区：
文献类型：
--
作者：
Perner S;Svensson MA;Hossain RR;Day JR;Groskopf J;Slaughter RC;Jarleborn AR;Hofer MD;Kuefer R;Demichelis F;Rickman DS;Rubin MA
前列腺癌（PCa）的一个特点是可以独立地产生不同的肿瘤病灶，这具有重要的生物学和临床意义。最近的研究表明，ERG重排的PCa具有灶内同质性，但灶间异质性支持这一假设。使用ERG重排作为克隆性的标志，我们询问多灶性PCa以确定其转移的倾向。我们研究了26例接受前列腺切除术和淋巴结切除术的患者，至少有两个不同的PCa病灶和一个淋巴结（LN）转移。评估每个病灶的大小、Gleason评分、ERG重排和TMPRSS 2-ERG转录。15/26例病例在ERG重排方面表现出灶间同质性（即，ERG重排的存在与不存在）。ERG重排6例全部阳性，9例全部阴性。两例病例显示了重排机制的病灶间异质性（即，通过插入或缺失的重排）。8/26例病例显示了重排状态的灶间异质性。在所有病例中，至少有一个ERG重排的焦点，我们发现相应的淋巴结转移窝藏ERG重排。有趣的是，在一个子集的情况下，在LN的重排状态并不对应于大小或Gleason评分。除了两个ERG重排病灶外，所有病灶均具有可检测的TMPRSS 2-ERG转录水平。当多灶性PCa同时显示ERG阳性和阴性病灶时，阳性病灶更易发生转移。需要更大规模的研究来证实ERG重新排列焦点对疾病进展可能性的潜在额外风险。
A hallmark of prostate cancer (PCa) is that distinct tumor foci may arise independently, which has important biologic and clinical implications. Recent studies characterizing ERG rearranged PCa possessing intrafocal homogeneity but interfocal heterogeneity support this hypothesis. Using ERG rearrangement as marker of clonality, we interrogated multifocal PCa to determine its predilection for metastasis. We studied 26 patients who underwent prostatectomy and lymphadenectomy with at least two distinct PCa foci and one lymph node (LN) metastasis. Each focus was assessed for size, Gleason score, ERG rearrangement, and TMPRSS2-ERG transcript. 15/26 cases exhibited interfocal homogeneity with regard to ERG rearrangement (i.e., presence versus absence of ERG rearrangement). ERG rearrangement was present in all foci for 6 and absent in all foci for 9 cases. Two cases revealed interfocal heterogeneity with regard to rearrangement mechanism (i.e., rearrangement through insertion or deletion). 8/26 cases revealed interfocal heterogeneity with regard to rearrangement status. In all cases with at least one ERG rearranged focus, we found the corresponding LN metastasis harboring an ERG rearrangement. Interestingly, in a subset of cases the rearrangement status in the LN did not correspond to size or Gleason score. All but two ERG rearranged foci had detectable TMPRSS2-ERG transcript levels. When multifocal PCa demonstrates both ERG positive and negative foci, the positive foci have a greater predilection for metastasis. Larger studies are needed to confirm the potential additional risk an ERG rearranged focus confers on the likelihood of disease progression.
登录
查看更多内容
影响因子：
30.8
作者：
Carver, Brett S.;Tran, Jennifer;Gopalan, Anuradha;Chen, Zhenbang;Shaikh, Safa;Carracedo, Arkaitz;Alimonti, Andrea;Nardella, Caterina;Varmeh, Shohreh;Scardino, Peter T.;Cordon-Cardo, Carlos;Gerald, William;Pandolfi, Pier Paolo
通讯作者：
Pandolfi, Pier Paolo
影响因子：
11.2
作者：
Gopalan A;Leversha MA;Satagopan JM;Zhou Q;Al-Ahmadie HA;Fine SW;Eastham JA;Scardino PT;Scher HI;Tickoo SK;Reuter VE;Gerald WL
通讯作者：
Gerald WL
影响因子：
11.2
作者：
Attard, Gerhardt;Swermenhuis, Joost F.;de Bono, Johann S.
通讯作者：
de Bono, Johann S.
影响因子：
7.5
作者：
Mehra, Rohit;Tomlins, Scott A.;Shah, Rajal B.
通讯作者：
Shah, Rajal B.
影响因子：
11.2
作者：
Mehra, Rohit;Tomlins, Scott A.;Chinnaiyan, Arul M.
通讯作者：
Chinnaiyan, Arul M.