- 迄今最大膀胱富脂质尿路上皮癌（LR-UC）系列：40 例，29 例有随访；2 年存活 55.6%（15/27），5 年存活 46%（12/26），侵袭性临床行为明显。
- 根治性切除与 OS 改善相关（P=0.0188），新辅助治疗有改善趋势；LR-UC 成分占比 >10% 者 OS 有下降趋势。
- 诊断陷阱：8 例中 6 例 LR-UC 与邻近普通 UC 均 MDM2 免疫组化阳性，1 例 FISH 证实 MDM2 扩增、1 例 RNA-ISH 过表达——膀胱内见脂母细胞样细胞且 MDM2 阳性时，勿据此误判为脂肪肉瘤。
- 9 对显微切割配对样本 RNA-seq：LR-UC 与其配对 UC 聚类，而非与他人的 LR 成分聚类，证实脂母细胞样细胞为尿路上皮来源；正向富集基因多为代谢相关，负向富集多为免疫/炎症相关。
收录范围：PubMed 英文摘要及中文翻译（abstract-only）。Unpaywall 无 OA 版本、Ovid 页无开放全文，未采集全文与图表。
摘要
富脂质尿路上皮癌（lipid-rich urothelial carcinoma，LR-UC）是一种罕见亚型，文献报道约 65 例。本文报告迄今最大的膀胱 LR-UC 病例系列，共 40 例患者。29 例有临床随访资料。27 例随访至少 2 年，其中 15 例 2 年时存活（55.6%）。26 例随访至少 5 年，其中 12 例 5 年时存活（46%）。根治性切除与总生存期（OS）改善相关（P=0.0188）。与单纯切除相比，新辅助治疗显示出改善 OS 的趋势。LR-UC 占比较高（>10%）的患者显示出 OS 降低的趋势。8 例肿瘤中有 6 例在 LR-UC 及邻近 UC 中均见 MDM2 免疫染色阳性，其中 1 例经 FISH 证实 MDM2 基因扩增，另有 1 例 MDM2 RNA-ISH 显示过表达。对 9 对显微切割的 LR-UC 与邻近 UC 配对样本进行了 RNA 测序。主成分分析显示，LR-UC 与其配对的 UC 聚类更近，而不是与其他患者的 LR 成分聚在一起。PRSS3P2 是唯一检测到在 LR-UC 中高于 UC 的成分。GSEA 分析显示，正向富集基因中 59.1% 与代谢相关，负向富集基因中 57.6% 与免疫/炎症相关。总之，本文报告了迄今最大的 LR-UC 系列，突出其侵袭性临床行为，并提示根治性手术切除和新辅助治疗可能获益。伴脂母细胞样细胞的 UC 表达 MDM2 可能构成诊断陷阱，转录组分析证实这些脂母细胞样细胞起源于 UC。
关键词：MDM2；PD-L1；组织学亚型；富脂质；尿路上皮癌
- Largest bladder LR-UC series to date: 40 patients, follow-up in 29; 2-year survival 55.6% (15/27), 5-year 46% (12/26) — an aggressive subtype.
- Definitive resection associated with improved OS (P=0.0188); neoadjuvant therapy showed a trend to benefit; LR-UC >10% trended to worse OS.
- Pitfall: MDM2 IHC positive in both LR-UC and adjacent UC in 6/8 tumors, with MDM2 amplification by FISH in one and RNA-ISH overexpression in another — lipoblast-like cells plus MDM2 positivity in the bladder should not be mistaken for liposarcoma.
- RNA-seq of 9 paired microdissected samples: LR-UC clustered with its paired UC rather than with other patients’ LR components, confirming urothelial origin; positively enriched genes were mostly metabolic, negatively enriched mostly immune/inflammatory.
Scope: PubMed abstract only. Unpaywall lists no OA copy and the Ovid page shows no open full text, so full text, figures and tables were not collected.
Abstract
Lipid-rich urothelial carcinoma (LR-UC) is a rare subtype, with ∼65 cases reported in the literature. Here, we report the largest case series of bladder LR-UC, including 40 patients. Clinical follow-up was available for 29 patients. Twenty-seven patients had at least 2-years follow-up, 15 of whom were alive (55.6%) at 2 years. Twenty-six patients had at least 5-years follow-up, 12 of whom were alive (46%) at 5 years. Definitive resection was associated with improved overall survival (OS) (P=0.0188). Neoadjuvant treatment showed a trend towards improved OS compared with resection alone. Patients with a higher percentage of LR-UC (>10%) showed a trend of decreased OS. Positive MDM2 immunostain in both LR-UC and adjacent UC was observed in 6 of 8 tumors, with MDM2 gene amplification confirmed by FISH in one case and MDM2 RNA-ISH overexpression in one additional case. RNA-seq was performed on 9 paired microdissected LR-UC and adjacent UC samples. Principal component analysis demonstrated LR-UC clustered with its paired UC more than with the LR component of other patients. PRSS3P2 was the only component detected to be higher in LR-UC than in UC. GSEA analysis demonstrated that 59.1% of positively enriched genes were metabolism-related, and 57.6% of negatively enriched genes were immune/inflammation-related. In summary, we report the largest LR-UC series to date, highlighting its aggressive clinical behavior, and suggesting a possible benefit of definitive surgical resection and neoadjuvant therapy. MDM2 expression in UC with lipoblast-like cells may pose a diagnostic pitfall and transcriptomic profiling confirm the UC origin lipoblast-like cells.
Keywords: MDM2; PD-L1; histologic subtype; lipid-rich; urothelial carcinoma