对低级别前列腺癌进行连续分子分析以评估肿瘤升级：一项纵向队列研究。
Serial Molecular Profiling of Low-grade Prostate Cancer to Assess Tumor Upgrading: A Longitudinal Cohort Study.
机构信息
Department of Urology, Michigan Medicine, Ann Arbor, MI, USA; University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA; Michigan Center for Translational Pathology, Michigan Medicine, Ann Arbor, MI, USA.
Department of Urology, Michigan Medicine, Ann Arbor, MI, USA; University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA; Michigan Center for Translational Pathology, Michigan Medicine, Ann Arbor, MI, USA.
出版信息
Eur Urol. 2021 Apr;79(4):456-465. doi: 10.1016/j.eururo.2020.06.041. Epub 2020 Jul 3.
BACKGROUND
The potential for low-grade (grade group 1 [GG1]) prostate cancer (PCa) to progress to high-grade disease remains unclear.
OBJECTIVE
To interrogate the molecular and biological features of low-grade PCa serially over time.
DESIGN, SETTING, AND PARTICIPANTS: Nested longitudinal cohort study in an academic active surveillance (AS) program. Men were on AS for GG1 PCa from 2012 to 2017.
INTERVENTION
Electronic tracking and resampling of PCa using magnetic resonance imaging/ultrasound fusion biopsy.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
ERG immunohistochemistry (IHC) and targeted DNA/RNA next-generation sequencing were performed on initial and repeat biopsies. Tumor clonality was assessed. Molecular data were compared between men who upgraded and those who did not upgrade to GG ≥ 2 cancer.
RESULTS AND LIMITATIONS
Sixty-six men with median age 64 yr (interquartile range [IQR], 59-69) and prostate-specific antigen 4.9 ng/mL (IQR, 3.3-6.4) underwent repeat sampling of a tracked tumor focus (median interval, 11 mo; IQR, 6-13). IHC-based ERG fusion status was concordant at initial and repeat biopsies in 63 men (95% vs expected 50%, p < 0.001), and RNAseq-based fusion and isoform expression were concordant in nine of 13 (69%) ERG patients, supporting focal resampling. Among 15 men who upgraded with complete data at both time points, integrated DNA/RNAseq analysis provided evidence of shared clonality in at least five cases. Such cases could reflect initial undersampling, but also support the possibility of clonal temporal progression of low-grade cancer. Our assessment was limited by sample size and use of targeted sequencing.
CONCLUSIONS
Repeat molecular assessment of low-grade tumors suggests that clonal progression could be one mechanism of upgrading. These data underscore the importance of serial tumor assessment in men pursuing AS of low-grade PCa.
PATIENT SUMMARY
We performed targeted rebiopsy and molecular testing of low-grade tumors on active surveillance. Our findings highlight the importance of periodic biopsy as a component of monitoring for cancer upgrading during surveillance.
背景
低级别（GG1）前列腺癌（PCa）进展为高级别疾病的潜力尚不清楚。
目的
随着时间的推移，连续检测低级别 PCa 的分子和生物学特征。
设计、地点和参与者：在学术主动监测（AS）计划中进行嵌套纵向队列研究。2012 年至 2017 年，男性因 GG1 PCa 接受 AS。
干预措施
使用磁共振成像/超声融合活检对 PCa 进行电子跟踪和重新取样。
结果测量和统计分析
对初始和重复活检进行 ERG 免疫组化（IHC）和靶向 DNA/RNA 下一代测序。评估肿瘤克隆性。比较升级和未升级为 GG≥2 癌症的男性之间的分子数据。
结果和局限性
66 名中位年龄 64 岁（四分位距 [IQR]，59-69）和前列腺特异性抗原 4.9ng/mL（IQR，3.3-6.4）的男性接受了跟踪肿瘤焦点的重复取样（中位间隔，11 个月；IQR，6-13）。在 63 名男性中，初始和重复活检的基于 IHC 的 ERG 融合状态具有一致性（95%比预期的 50%，p<0.001），在 13 名 ERG 患者中的 9 名（69%）中，基于 RNAseq 的融合和异构体表达具有一致性，支持焦点取样。在 15 名在两个时间点均有完整数据升级的男性中，综合 DNA/RNAseq 分析至少在 5 例中提供了共享克隆性的证据。这种情况可能反映了初始取样不足，但也支持低级别癌症克隆时间进展的可能性。我们的评估受到样本量和靶向测序的限制。
结论
对低级别肿瘤进行重复分子评估表明，克隆进展可能是升级的一种机制。这些数据强调了在低级别 PCa 主动监测中定期进行肿瘤评估的重要性。
患者总结
我们对主动监测中的低级别肿瘤进行了靶向重新活检和分子检测。我们的发现强调了定期活检作为监测期间癌症升级监测的一部分的重要性。
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