Department of Surgery, University of Melbourne, Parkville, Victoria, Australia; Urology Unit, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Bioinformatics Division, Walter & Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia; Department of Computing and Information Systems, University of Melbourne, Melbourne, Victoria, Australia.
Eur J Cancer. 2021 May;148:440-450. doi: 10.1016/j.ejca.2020.12.030. Epub 2021 Mar 5.
Ductal adenocarcinoma is an uncommon prostate cancer variant. Previous studies suggest that ductal variant histology may be associated with worse clinical outcomes, but these are difficult to interpret. To address this, we performed an international, multi-institutional study to describe the characteristics of ductal adenocarcinoma, particularly focussing on the effect of presence of ductal variant cancer on metastasis-free survival.
Patients with ductal variant histology from two institutional databases who underwent radical prostatectomies were identified and compared with an independent acinar adenocarcinoma cohort. After propensity score matching, the effect of the presence of ductal adenocarcinoma on time to biochemical recurrence, initiation of salvage therapy and the development of metastatic disease was determined. Deep whole-exome sequencing was performed for selected cases (n = 8).
A total of 202 ductal adenocarcinoma and 2037 acinar adenocarcinoma cases were analysed. Survival analysis after matching demonstrated that patients with ductal variant histology had shorter salvage-free survival (8.1 versus 22.0 months, p = 0.03) and metastasis-free survival (6.7 versus 78.6 months, p < 0.0001). Ductal variant histology was consistently associated with RB1 loss, as well as copy number gains in TAP1, SLC4A2 and EHHADH.
The presence of any ductal variant adenocarcinoma at the time of prostatectomy portends a worse clinical outcome than pure acinar cancers, with significantly shorter times to initiation of salvage therapies and the onset of metastatic disease. These features appear to be driven by uncoupling of chromosomal duplication from cell division, resulting in widespread copy number aberration with specific gain of genes implicated in treatment resistance.
管状腺癌是一种罕见的前列腺癌变体。先前的研究表明，管状变体组织学可能与更差的临床结果相关，但这些结果难以解释。为了解决这个问题，我们进行了一项国际多机构研究，描述了管状腺癌的特征，特别是重点关注管状变体癌的存在对无转移生存的影响。
从两个机构数据库中确定了接受根治性前列腺切除术的管状变体组织学患者，并与独立的腺泡腺癌队列进行了比较。在进行倾向评分匹配后，确定了管状腺癌的存在对生化复发时间、挽救治疗开始时间和转移性疾病发展的影响。对选定病例（n=8）进行了深度全外显子组测序。
共分析了 202 例管状腺癌和 2037 例腺泡腺癌病例。匹配后的生存分析表明，具有管状变体组织学的患者挽救无复发生存率（8.1 个月与 22.0 个月，p=0.03）和无转移生存率（6.7 个月与 78.6 个月，p<0.0001）更短。管状变体组织学始终与 RB1 缺失以及 TAP1、SLC4A2 和 EHHADH 的拷贝数增益相关。
前列腺切除时存在任何管状变体腺癌预示着比纯腺泡癌更差的临床结果，挽救治疗和转移性疾病的起始时间明显缩短。这些特征似乎是由于染色体复制与细胞分裂脱偶联引起的，导致广泛的拷贝数异常，特定增益与治疗抵抗相关的基因。
