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Int J Mol Sci ; 19(9)2018 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-30154342

RESUMEN

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. N = 142 (n = 82 pTa, n = 42 pT1, n = 18 pT2-4) morphologically G1⁻G3 tumors were analyzed for immunohistochemical expression of FGFR3 and Ki67. Mutation analysis of FGFR3 and TP53 and FISH for FGFR3 amplification and rearrangement was performed. SPSS 23.0 was used for statistical analysis. Overall FGFR3high/Ki67high status (n = 58) resulted in a reduced ∆mean progression-free survival (PFS) (p < 0.01) of 63.92 months, and shorter progression-free survival (p < 0.01; mean PFS: 55.89 months) in pTa tumors (n = 50). FGFR3mut/TP53mut double mutations led to a reduced ∆mean PFS (p < 0.01) of 80.30 months in all tumors, and FGFR3mut/TP53mut pTa tumors presented a dramatically reduced PFS (p < 0.001; mean PFS: 5.00 months). Our results identified FGFR3high/Ki67high 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.


Asunto(s)
Carcinoma Papilar/diagnóstico , Carcinoma Papilar/metabolismo , Antígeno Ki-67/metabolismo , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/metabolismo , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/metabolismo , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Carcinoma Papilar/genética , Carcinoma Papilar/mortalidad , Femenino , Humanos , Inmunohistoquímica , Antígeno Ki-67/genética , Masculino , Persona de Mediana Edad , Mutación , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética , Transducción de Señal , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/mortalidad
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