Increased gene copy number of ERG on chromosome 21 but not TMPRSS2-ERG fusion predicts outcome in prostatic adenocarcinomas.
Increased gene copy number of ERG on chromosome 21 but not TMPRSS2-ERG fusion predicts outcome in prostatic adenocarcinomas.
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DOI：
10.1038/modpathol.2011.111
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发表时间：
2011-11
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TMPRSS 2-ERG基因融合在前列腺癌发生发展中的作用仍存在争议。我们在一项嵌套在约翰霍普金斯耻骨后根治性膀胱切除术队列中的病例对照研究中，使用荧光原位杂交分析评估了TMPRSS 2-ERG融合的预后作用。总共分析了10个组织微阵列，其中包含从172例（复发）和172例对照（非复发）中获得的配对肿瘤和正常组织，这些病例在病理学分级、分期、种族/民族和手术时的年龄上匹配。1993年至2004年期间，所有根治性前列腺切除术均在本机构进行。复发定义为生化复发、出现转移的临床证据或前列腺癌死亡。对每个组织微阵列点的TMPRSS 2-ERG基因融合的存在和ERG基因拷贝数增加进行评分。复发的比值比和95%可信区间由条件Logistic回归估计。尽管病例中融合的病例百分比略低于对照组（50 vs 57%），但差异无统计学显著性（P=0.20）。由于缺失或分裂事件而出现的融合与复发无关。类似地，存在重复ERG缺失、重复ERG分裂或ERG基因拷贝数增加与单个ERG融合与复发无关。未融合的ERG基因多体性与复发显著相关（比值比2.0，95%置信区间1.17-3.42）。总之，TMPRSS 2-ERG融合对临床局限性前列腺癌行耻骨后根治性前列腺切除术后的复发无预后意义，尽管ERG基因拷贝数增加而未融合的男性复发的可能性高两倍。
The role of TMPRSS2–ERG gene fusion in prostate cancer prognostication remains controversial. We evaluated the prognostic role of TMPRSS2–ERG fusion using fluorescence in situ hybridization analysis in a case–control study nested in The Johns Hopkins retropubic radical prostatectomy cohort. In all, 10 tissue microarrays containing paired tumors and normal tissues obtained from 172 cases (recurrence) and 172 controls (non-recurrence) matched on pathological grade, stage, race/ethnicity, and age at the time of surgery were analyzed. All radical prostatectomies were performed at our institution between 1993 and 2004. Recurrence was defined as biochemical recurrence, development of clinical evidence of metastasis, or death from prostate carcinoma. Each tissue microarray spot was scored for the presence of TMPRSS2–ERG gene fusion and for ERG gene copy number gains. The odds ratio of recurrence and 95% confidence intervals were estimated from conditional logistic regression. Although the percentage of cases with fusion was slightly lower in cases than in controls (50 vs 57%), the difference was not statistically significant (P=0.20). The presence of fusion due to either deletion or split event was not associated with recurrence. Similarly, the presence of duplicated ERG deletion, duplicated ERG split, or ERG gene copy number gain with a single ERG fusion was not associated with recurrence. ERG gene polysomy without fusion was significantly associated with recurrence (odds ratio 2.0, 95% confidence interval 1.17–3.42). In summary, TMPRSS2–ERG fusion was not prognostic for recurrence after retropubic radical prostatectomy for clinically localized prostate cancer, although men with ERG gene copy number gain without fusion were twice more likely to recur.
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