Diagnostic and Prognostic Implications of FGFR3high/Ki67high Papillary Bladder Cancers
Abstract
:1. Introduction
2. Results
2.1. Immunohistochemical Combination of Ki67-Index and FGFR3 Levels Defines Worse Patients’ Outcome
2.2. Prognostic Impact of Ki67-Index and FGFR3 Overexpression in Papillary Non-Invasive (pTa) Tumors
2.3. Altered Molecular FGFR3/TP53 Status Predicts Worse Patients’ Survival
2.4. Prognostic Impact of FGFR3 and TP53 Mutations in Papillary Non-Invasive (pTa) Tumors
2.5. FGFR3high/Ki67high Tumors Define a Subset of pTa Tumors Including Lesions with Molecular FGFR3 Pathway Activation
3. Discussion
4. Materials and Methods
4.1. Patient Samples, Tissue Microarrays and DNA
4.2. Immunohistochemistry
4.3. Fluorescence In Situ Hybridization
4.4. Sanger Sequencing
4.5. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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FGFR3 Expression a | |||||
---|---|---|---|---|---|
n | 0–2 | 3 | p-Value b | Spearman ρ | |
Parameter: | |||||
Age at diagnosis | |||||
<70 years | 67 | 20 | 47 | 0.946 | 0.006 |
≥70 years | 75 | 22 | 53 | ||
Gender | |||||
female | 31 | 10 | 21 | 0.372 | 0.031 |
male | 111 | 32 | 79 | ||
Histological tumor grade | |||||
low grade | 49 | 3 | 46 | <0.001 | −0.373 |
high grade | 93 | 39 | 54 | ||
Tumor stage | |||||
pTa | 82 | 14 | 68 | <0.001 | −0.320 |
pT1–pT4 | 60 | 28 | 32 |
Ki67 Expression a | |||||
---|---|---|---|---|---|
n | <15% | ≥15% | p-Value b | Spearman ρ | |
Parameter: | |||||
Age at diagnosis | |||||
<70 years | 67 | 31 | 36 | 0.083 | 0.146 |
≥70 years | 75 | 24 | 51 | ||
Gender | |||||
female | 31 | 14 | 17 | 0.408 | 0.070 |
male | 111 | 41 | 70 | ||
Histological tumor grade | |||||
low grade | 49 | 34 | 15 | <0.001 | 0.457 |
high grade | 93 | 21 | 72 | ||
Tumor stage | |||||
pTa | 82 | 37 | 45 | 0.069 | 0.175 |
pT1–pT4 | 60 | 18 | 42 |
Variable | HR | p-Value | 95%CI | |
---|---|---|---|---|
Lower | Upper | |||
FGFR3 high/Ki67high | 3.943 | 0.019 | 1.247 | 12.466 |
pT status | 0.957 | 0.941 | 0.295 | 3.105 |
Tumor grade | 0.846 | 0.823 | 0.196 | 3.653 |
Keratin 5/6 | 0.482 | 0.280 | 0.128 | 1.812 |
Keratin 20 | 0.424 | 0.115 | 0.146 | 1.232 |
Age | 1.773 | 0.347 | 0.537 | 5.847 |
Variable | HR | p-Value | 95%CI | |
---|---|---|---|---|
Lower | Upper | |||
FGFR3mut/TP53mut | 6.563 | 0.006 | 1.694 | 25.425 |
pT status | 1.179 | 0.821 | 0.284 | 4.896 |
Tumor grade | 0.241 | 0.138 | 0.037 | 1.580 |
Keratin 5/6 | 0.714 | 0.621 | 0.188 | 2.712 |
Keratin 20 | 0.872 | 0.814 | 0.279 | 2.730 |
Age | 1.41 | 0.584 | 0.412 | 2.809 |
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Geelvink, M.; Babmorad, A.; Maurer, A.; Stöhr, R.; Grimm, T.; Bach, C.; Knuechel, R.; Rose, M.; Gaisa, N.T. Diagnostic and Prognostic Implications of FGFR3high/Ki67high Papillary Bladder Cancers. Int. J. Mol. Sci. 2018, 19, 2548. https://doi.org/10.3390/ijms19092548
Geelvink M, Babmorad A, Maurer A, Stöhr R, Grimm T, Bach C, Knuechel R, Rose M, Gaisa NT. Diagnostic and Prognostic Implications of FGFR3high/Ki67high Papillary Bladder Cancers. International Journal of Molecular Sciences. 2018; 19(9):2548. https://doi.org/10.3390/ijms19092548
Chicago/Turabian StyleGeelvink, Mirja, Armin Babmorad, Angela Maurer, Robert Stöhr, Tobias Grimm, Christian Bach, Ruth Knuechel, Michael Rose, and Nadine T. Gaisa. 2018. "Diagnostic and Prognostic Implications of FGFR3high/Ki67high Papillary Bladder Cancers" International Journal of Molecular Sciences 19, no. 9: 2548. https://doi.org/10.3390/ijms19092548