Rostad Kari, Hellwinkel Olaf J C, Haukaas Svein A, Halvorsen Ole J, Øyan Anne M, Haese Alexander, Budäus Lars, Albrecht Heiko, Akslen Lars A, Schlomm Thorsten, Kalland Karl-Henning
The Gade Institute, University of Bergen, Bergen, Norway.
APMIS. 2009 Aug;117(8):575-82. doi: 10.1111/j.1600-0463.2009.02517.x.
The transcription factor ERG is highly upregulated in the majority of prostate cancers due to chromosomal fusion of the androgen responsive promoter of TMPRSS2 to the ERG reading frame. Our aim was to identify this gene fusion in urine samples from prostate cancer patients prior to radical treatment and to compare fusion status with clinicopathological variables. Urine fractions from 55 patients (with and without prior prostatic massage) were analyzed for the presence of TMPRSS2:ERG isoforms using real-time qPCR. Sixty-nine percent of urine samples following prostatic massage were positive for TMPRSS2:ERG isoforms a or b, five out of which were positive for both, vs 24% of samples obtained without prior massage. Isoform a seems to be most prevalent and some patients may be positive for more than one fusion variant, reflecting the multifocality of prostate cancer. Prostatic massage prior to sampling, analysis of pelleted urine material and detection of cDNA provided the highest sensitivity. Positive statistical correlations were identified between TMPRSS2:ERG fusion and high s-PSA, pathological stage and Gleason score. Our findings contribute to the increasing elucidation of the role of TMPRSS2:ERG in the development of prostate cancer.
由于TMPRSS2的雄激素反应性启动子与ERG读码框发生染色体融合，转录因子ERG在大多数前列腺癌中高度上调。我们的目的是在根治性治疗前从前列腺癌患者的尿液样本中鉴定这种基因融合，并将融合状态与临床病理变量进行比较。使用实时定量PCR分析了55例患者（有或没有前列腺按摩史）的尿液成分中TMPRSS2:ERG异构体的存在情况。前列腺按摩后的尿液样本中，69%的样本TMPRSS2:ERG异构体a或b呈阳性，其中5例两种异构体均为阳性，而未进行前列腺按摩的样本中这一比例为24%。异构体a似乎最为常见，一些患者可能不止一种融合变体呈阳性，这反映了前列腺癌的多灶性。采样前进行前列腺按摩、分析沉淀的尿液物质以及检测cDNA可提供最高的灵敏度。TMPRSS2:ERG融合与高血清前列腺特异抗原、病理分期和 Gleason评分之间存在正相关。我们的研究结果有助于进一步阐明TMPRSS2:ERG在前列腺癌发生发展中的作用。
