Aggressive-variant prostate cancers(AVPCs) are a subset of metastatic castrate-resistant prostate cancers (mCRPCs) characterized by defects in ≥ two of three ofTP53,RB1, andPTEN(AVPCm), a profile linked to lineage plasticity, androgen indifference, and platinum sensitivity. Men with mCRPC undergoing biopsies for progression were assessed for AVPCm using immunohistochemistry (IHC), next-generation sequencing (NGS) of solid tumor DNA (stDNA), and NGS of circulating tumor DNA (ctDNA) assays in CLIA-certified labs. Biopsy characteristics, turnaround times, inter-reader concordance, and inter-assay concordance were assessed. AVPCm was detected in 13 (27%) patients via IHC, two (6%) based on stDNA, and seven (39%) based on ctDNA. The concordance of the IHC reads between pathologists was variable. IHC had a higher detection rate of AVPCm+tumors with the shortest turnaround times. stDNA had challenges with copy number loss detection, limiting its detection rate. ctDNA detected the greatest proportion of AVPCm+tumors but had a low tumor content in two thirds of patients. These data show the operational characteristics of AVPCm detection using various assays, and inform trial design using AVPCm as a criterion for patient selection or stratification.
侵袭性变异前列腺癌（AVPCs）是转移性去势抵抗性前列腺癌（mCRPCs）的一个亚型，其特征为TP53、RB1和PTEN三个基因中至少两个存在缺陷（AVPCm），这一特征与谱系可塑性、雄激素不敏感性和铂类药物敏感性相关。本研究对因疾病进展接受活检的mCRPC患者，通过经CLIA认证实验室的免疫组织化学（IHC）、实体瘤DNA（stDNA）二代测序（NGS）以及循环肿瘤DNA（ctDNA）NGS检测进行AVPCm评估。分析了活检特征、检测周期、阅片者间一致性及检测方法间一致性。结果显示：通过IHC在13例（27%）患者中检出AVPCm，基于stDNA检出2例（6%），基于ctDNA检出7例（39%）。病理学家间的IHC判读一致性存在差异。IHC对AVPCm阳性肿瘤的检出率最高且检测周期最短。stDNA在拷贝数缺失检测方面存在技术局限，限制了其检出率。ctDNA检出的AVPCm阳性肿瘤比例最高，但三分之二患者的肿瘤含量较低。这些数据揭示了不同检测方法在AVPCm检测中的操作特性，为将AVPCm作为患者筛选或分层标准的临床试验设计提供了依据。
肿瘤(癌症)患者之家