Junker Kerstin, van Oers Johanna M M, Zwarthoff Ellen C, Kania Ines, Schubert Joerg, Hartmann Arndt
Klinik für Urologie, Universität, Jena.
Verh Dtsch Ges Pathol. 2006;90:151-8.
It has been suggested that mutation of FGFR3 is associated with non-invasive tumors of low malignant potential and low risk of recurrence and progression. The aim of this study was to analyze the distribution of FGFR3 mutations in bladder tumors of different grade and stage and to determine the relation of FGFR3 mutations to chromosomal alterations detected by CGH. Frozen sections of 100 bladder cancer samples served as templates for manual microdissection. DNA was isolated from dissected samples containing at least 80% tumor cells. Mutations in FGFR3 were analyzed by SNaPshot analysis. CGH was carried out according to standard protocols. FGFR3 mutations were detected in 45 out of 92 samples (48.9 %). Concerning T-category, the following mutation frequencies occurred: pTa - 69 %, pT1 - 38 %, pT2/3 - 0 %. The mutation frequency was significantly associated with tumor grade: G1 - 72%, G2 - 56%, G3 - 4%. In pTaG1 tumors, mutations were found in 74 %. A significant lower number of genetic alterations per tumor detected by CGH was associated with FGFR3 mutations (2 vs. 8). This association was also seen in pTaG1 tumors: 2.5 (with mutation) vs. 7.5 (without mutation). Our results confirm that FGFR3 mutations characterize non-invasive low-risk tumors of low malignancy. The low malignant potential of these tumors is underlined by a low number of chromosomal alterations per tumor. Therefore, FGFR3 could represent a prognostic marker of chromosomally stable tumors with low malignant potential.
有人提出,FGFR3突变与低恶性潜能、低复发和进展风险的非侵袭性肿瘤相关。本研究的目的是分析FGFR3突变在不同分级和分期膀胱肿瘤中的分布,并确定FGFR3突变与CGH检测到的染色体改变之间的关系。100例膀胱癌样本的冰冻切片用作手动显微切割的模板。从含有至少80%肿瘤细胞的切割样本中分离DNA。通过SNaPshot分析检测FGFR3突变。按照标准方案进行CGH。在92个样本中的45个(48.9%)检测到FGFR3突变。关于T分期,出现以下突变频率:pTa - 69%,pT1 - 38%,pT2/3 - 0%。突变频率与肿瘤分级显著相关:G1 - 72%,G2 - 56%,G3 - 4%。在pTaG1肿瘤中,74%发现有突变。CGH检测到的每个肿瘤的基因改变数量显著减少与FGFR3突变相关(2个对8个)。这种关联在pTaG1肿瘤中也可见:2.5个(有突变)对7.5个(无突变)。我们的结果证实,FGFR3突变是低恶性非侵袭性低风险肿瘤的特征。这些肿瘤的低恶性潜能通过每个肿瘤的染色体改变数量少得到强调。因此,FGFR3可能代表具有低恶性潜能的染色体稳定肿瘤的预后标志物。