Laboratory of Genomic Medicine, Department of Pathology, University of Illinois at Chicago (UIC) College of Medicine, Chicago, Illinois.
Laboratory of Genomic Medicine, Department of Pathology, University of Illinois at Chicago (UIC) College of Medicine, Chicago, Illinois.
Mod Pathol. 2023 Jun;36(6):100130. doi: 10.1016/j.modpat.2023.100130. Epub 2023 Feb 13.
Intraductal carcinoma (IDC) of the prostate is often associated with concurrent high-grade invasive prostate cancer (PCa) and poor clinical outcomes. In this context, IDC is thought to represent the retrograde spread of invasive prostatic adenocarcinoma into the acini and ducts. Prior studies have demonstrated a concordance of PTEN loss and genomic instability between the IDC and high-grade invasive components of PCa, but larger genomic association studies to solidify our understanding of the relationship between these 2 lesions are lacking. Here, we evaluate the genomic relationship between duct-confined (high-grade prostatic intraepithelial neoplasia and IDC) and invasive components of high-grade PCa using genetic variants generated by whole exome sequencing. High-grade prostatic intraepithelial neoplasia and IDC were laser-microdissected, and PCa and nonneoplastic tissue was manually dissected from 12 radical prostatectomies. A targeted next-generation sequencing panel was used to identify disease-relevant variants. Additionally, the degree of overlap between adjacent lesions was determined by comparing exome-wide variants detected using whole exome sequencing data. Our results demonstrate that IDC and invasive high-grade PCa components show common genetic variants and copy number alterations. Hierarchical clustering of genome-wide variants suggests that in these tumors, IDC is more closely related to the high-grade invasive components of the tumor compared with high-grade prostatic intraepithelial neoplasia. In conclusion, this study reinforces the concept that, in the context of high-grade PCa, IDC likely represents a late event associated with tumor progression.
前列腺导管内癌（IDC）常与同时存在的高级别浸润性前列腺癌（PCa）和不良临床结局相关。在这种情况下，IDC 被认为代表了侵袭性前列腺腺癌逆行扩散到腺泡和导管中。先前的研究表明，IDC 与 PCa 的高级别浸润成分之间存在 PTEN 缺失和基因组不稳定性的一致性，但缺乏更大的基因组关联研究来巩固我们对这两种病变之间关系的理解。在这里，我们使用全外显子组测序产生的遗传变异来评估导管内受限（高级别前列腺上皮内瘤变和 IDC）和高级别 PCa 的浸润成分之间的基因组关系。激光微切割高级别前列腺上皮内瘤变和 IDC，手动从 12 例根治性前列腺切除术分离 PCa 和非肿瘤组织。使用靶向下一代测序面板来鉴定与疾病相关的变异。此外，通过比较使用全外显子组测序数据检测到的外显子全范围内的变异来确定相邻病变之间的重叠程度。我们的结果表明，IDC 和侵袭性高级别 PCa 成分显示出共同的遗传变异和拷贝数改变。全基因组变异的层次聚类表明，在这些肿瘤中，与高级别前列腺上皮内瘤变相比，IDC 与肿瘤的高级别浸润成分更为密切相关。总之，这项研究强化了这样一种概念，即在高级别 PCa 的背景下，IDC 可能代表与肿瘤进展相关的晚期事件。
