Institute of Pathology, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany.
Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
Int J Mol Sci. 2018 Aug 28;19(9):2548. doi: 10.3390/ijms19092548.
Prognostic/therapeutic stratification of papillary urothelial cancers is solely based upon histology, despite activated FGFR3-signaling was found to be associated with low grade tumors and favorable outcome. However, there are FGFR3-overexpressing tumors showing high proliferation-a paradox of coexisting favorable and adverse features. Therefore, our study aimed to decipher the relevance of FGFR3-overexpression/proliferation for histopathological grading and risk stratification. = 142 ( = 82 pTa, = 42 pT1, = 18 pT2-4) morphologically G1⁻G3 tumors were analyzed for immunohistochemical expression of FGFR3 and Ki67. Mutation analysis of and and FISH for amplification and rearrangement was performed. SPSS 23.0 was used for statistical analysis. Overall FGFR3/Ki67 status ( = 58) resulted in a reduced ∆mean progression-free survival (PFS) ( < 0.01) of 63.92 months, and shorter progression-free survival ( < 0.01; mean PFS: 55.89 months) in pTa tumors ( = 50). / double mutations led to a reduced ∆mean PFS ( < 0.01) of 80.30 months in all tumors, and / pTa tumors presented a dramatically reduced PFS ( < 0.001; mean PFS: 5.00 months). Our results identified FGFR3/Ki67 papillary pTa tumors as a subgroup with poor prognosis and encourage histological grading as high grade tumors. Tumor grading should possibly be augmented by immunohistochemical stainings and suitable clinical surveillance by endoscopy should be performed.
乳头状尿路上皮癌的预后/治疗分层仅基于组织学,尽管已发现激活的 FGFR3 信号与低级别肿瘤和有利的结果相关。然而,有 FGFR3 过表达的肿瘤表现出高增殖——共存有利和不利特征的悖论。因此,我们的研究旨在阐明 FGFR3 过表达/增殖与组织病理学分级和风险分层的相关性。 = 142( = 82 pTa, = 42 pT1, = 18 pT2-4)形态学 G1⁻G3 肿瘤进行 FGFR3 和 Ki67 的免疫组织化学表达分析。对 和 进行突变分析,对 进行 FISH 检测扩增和重排。使用 SPSS 23.0 进行统计分析。总体 FGFR3/Ki67 状态( = 58)导致无进展生存期(PFS)( < 0.01)的 ∆均值显著降低(63.92 个月),pTa 肿瘤( = 50)的 PFS 更短( < 0.01;平均 PFS:55.89 个月)。 / 双突变导致所有肿瘤的 ∆均值 PFS( < 0.01)降低 80.30 个月, / pTa 肿瘤的 PFS 明显降低( < 0.001;平均 PFS:5.00 个月)。我们的结果确定 FGFR3/Ki67 乳头状 pTa 肿瘤为预后不良的亚组,并鼓励将组织学分级为高级别肿瘤。肿瘤分级可能需要通过免疫组织化学染色来增强,并且应通过内窥镜进行适当的临床监测。