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Diagnostic and Prognostic Implications of FGFR3 high /Ki67 high Papillary Bladder Cancers.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2018 Aug 28; Vol. 19 (9). Date of Electronic Publication: 2018 Aug 28. - Publication Year :
- 2018
-
Abstract
- 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 FGFR3 <superscript>high</superscript> /Ki67 <superscript>high</superscript> 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). FGFR3 <superscript>mut</superscript> / TP53 <superscript>mut</superscript> double mutations led to a reduced ∆mean PFS ( p < 0.01) of 80.30 months in all tumors, and FGFR3 <superscript>mut</superscript> / TP53 <superscript>mut</superscript> pTa tumors presented a dramatically reduced PFS ( p < 0.001; mean PFS: 5.00 months). Our results identified FGFR3 <superscript>high</superscript> /Ki67 <superscript>high</superscript> 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.
- Subjects :
- Aged
Aged, 80 and over
Biomarkers, Tumor
Carcinoma, Papillary genetics
Carcinoma, Papillary mortality
Female
Humans
Immunohistochemistry
Ki-67 Antigen genetics
Male
Middle Aged
Mutation
Neoplasm Grading
Neoplasm Staging
Prognosis
Proportional Hazards Models
Receptor, Fibroblast Growth Factor, Type 3 genetics
Signal Transduction
Tumor Suppressor Protein p53 genetics
Tumor Suppressor Protein p53 metabolism
Urinary Bladder Neoplasms genetics
Urinary Bladder Neoplasms mortality
Carcinoma, Papillary diagnosis
Carcinoma, Papillary metabolism
Ki-67 Antigen metabolism
Receptor, Fibroblast Growth Factor, Type 3 metabolism
Urinary Bladder Neoplasms diagnosis
Urinary Bladder Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 19
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 30154342
- Full Text :
- https://doi.org/10.3390/ijms19092548