Giedl Johannes, Wild Peter J, Stoehr Robert, Junker Kerstin, Boehm Stefan, van Oers Johanna M M, Zwarthoff Ellen C, Blaszyk Hagen, Fine Samson W, Humphrey Peter A, Dehner Louis P, Amin Mahul B, Epstein Jonathan I, Hartmann Arndt
Institut für Pathologie, Universität Regensburg, Regensburg.
Verh Dtsch Ges Pathol. 2006;90:253-63.
Urothelial neoplasms in patients 19 years or younger are rare, with conflicting data regarding clinical outcome and no molecular data available.
Urothelial tumors of 14 patients 4 to 19 years old were identified, reclassified according to the 2004 WHO classification and data on presentation, risk factors and outcome were collected. 14 cases were microdissected and extensive molecular analyses were done, including FGFR3 and TP 53 mutation screening, Comparative Genomic Hybridisation (CGH), Urovysion FISH analysis, PCR for HPV, microsatellite analysis using an extended NIH consensus panel for detection of microsatellite instability (MSI) and 6 LOH markers on chromosome arms 17p, 9p and 9q and immunohistochemistry for TP 53, MIB1, CK20 and the mismatch repair proteins hMSH2, hMLH1 and hMSH6.
Based on the 2004 WHO classification, 1 urothelial papilloma, 7 PUNLMPs, 5 low grade, and 1 high grade papillary urothelial cancers were included. There were no multifocal tumors and only 1 patient had recurrence. All patients were alive with no evidence of disease (4.5 years follow-up). We did not find mutations in FGFR3, deletions of chromosome arms 9p, 9q or 17p, MSI or MRP loss or HPV positivity. Chromosomal alterations in CGH, urothelial dedifferentiation with CK20 over-expression or aneuploidy were rare and only detected in 3 cases. One TP53 mutation was found in the only tumor with overexpression of TP53.
Urothelial neoplasms in individuals younger than 20 years have predominantly a low grade and favourable clinical outcome. The most frequent genetic alterations found in elderly patients are extremely rare. Urothelial neoplasms in young patients could represent a biologically distinct form of bladder disease with lack of genetic instability in most cases.
19岁及以下患者的尿路上皮肿瘤罕见，关于临床结果的数据相互矛盾，且尚无分子数据。
确定了14例4至19岁患者的尿路上皮肿瘤，根据2004年世界卫生组织分类进行重新分类，并收集了关于临床表现、危险因素和结果的数据。对14例病例进行显微切割，并进行了广泛的分子分析，包括FGFR3和TP 53突变筛查、比较基因组杂交（CGH）、Urovysion荧光原位杂交（FISH）分析、HPV聚合酶链反应（PCR）、使用扩展的美国国立卫生研究院共识面板检测微卫星不稳定性（MSI）的微卫星分析以及17号染色体短臂、9号染色体短臂和9号染色体长臂上的6个杂合性缺失（LOH）标记，以及TP 53、MIB1、CK20和错配修复蛋白hMSH2、hMLH1和hMSH6的免疫组织化学分析。
根据2004年世界卫生组织分类，包括1例尿路上皮乳头状瘤、7例低度恶性潜能尿路上皮瘤、5例低级别和1例高级别乳头状尿路上皮癌。无多灶性肿瘤，仅1例患者复发。所有患者均存活，无疾病证据（随访4.5年）。我们未发现FGFR3突变、9号染色体短臂、9号染色体长臂或17号染色体短臂缺失、MSI或错配修复蛋白缺失或HPV阳性。CGH中的染色体改变、CK20过度表达或非整倍体导致的尿路上皮去分化很少见，仅在3例中检测到。在唯一的TP53过度表达的肿瘤中发现1个TP53突变。
20岁以下个体的尿路上皮肿瘤主要为低级别，临床结果良好。老年患者中最常见的基因改变极为罕见。年轻患者的尿路上皮肿瘤可能代表一种生物学上独特的膀胱疾病形式，大多数情况下缺乏基因不稳定性。
