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Chromosome 9p deletion in clear cell renal cell carcinoma predicts recurrence and survival following surgery

BACKGROUND: Wider clinical applications of 9p status in clear cell renal cell carcinoma (ccRCC) are limited owing to the lack of validation and consensus for interphase fluorescent in situ hybridisation (I-FISH) scoring technique. The aim of this study was to analytically validate the applicability...

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Autores principales: El-Mokadem, I, Fitzpatrick, J, Bondad, J, Rauchhaus, P, Cunningham, J, Pratt, N, Fleming, S, Nabi, G
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183850/
https://www.ncbi.nlm.nih.gov/pubmed/25137021
http://dx.doi.org/10.1038/bjc.2014.420
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author El-Mokadem, I
Fitzpatrick, J
Bondad, J
Rauchhaus, P
Cunningham, J
Pratt, N
Fleming, S
Nabi, G
author_facet El-Mokadem, I
Fitzpatrick, J
Bondad, J
Rauchhaus, P
Cunningham, J
Pratt, N
Fleming, S
Nabi, G
author_sort El-Mokadem, I
collection PubMed
description BACKGROUND: Wider clinical applications of 9p status in clear cell renal cell carcinoma (ccRCC) are limited owing to the lack of validation and consensus for interphase fluorescent in situ hybridisation (I-FISH) scoring technique. The aim of this study was to analytically validate the applicability of I-FISH in assessing 9p deletion in ccRCC and to clinically assess its long-term prognostic impact following surgical excision of ccRCC. METHODS: Tissue microarrays were constructed from 108 renal cell carcinoma (RCC) tumour paraffin blocks. Interphase fluorescent in situ hybridisation analysis was undertaken based on preset criteria by two independent observers to assess interobserver variability. 9p status in ccRCC tumours was determined and correlated to clinicopathological variables, recurrence-free survival and disease-specific survival. RESULTS: There were 80 ccRCCs with valid 9p scoring and a median follow-up of 95 months. Kappa statistic for interobserver variability was 0.71 (good agreement). 9p deletion was detected in 44% of ccRCCs. 9p loss was associated with higher stage, larger tumours, necrosis, microvascular and renal vein invasion, and higher SSIGN (stage, size, grade and necrosis) score. Patients with 9p-deleted ccRCC were at a higher risk of recurrence (P=0.008) and RCC-specific mortality (P=0.001). On multivariate analysis, 9p deletion was an independent predictor of recurrence (hazard ratio 4.323; P=0.021) and RCC-specific mortality (hazard ratio 4.603; P=0.007). The predictive accuracy of SSIGN score improved from 87.7% to 93.1% by integrating 9p status to the model (P=0.001). CONCLUSIONS: Loss of 9p is associated with aggressive ccRCC and worse prognosis in patients following surgery. Our findings independently confirm the findings of previous reports relying on I-FISH to detect 9p (CDKN2A) deletion.
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spelling pubmed-41838502015-09-23 Chromosome 9p deletion in clear cell renal cell carcinoma predicts recurrence and survival following surgery El-Mokadem, I Fitzpatrick, J Bondad, J Rauchhaus, P Cunningham, J Pratt, N Fleming, S Nabi, G Br J Cancer Molecular Diagnostics BACKGROUND: Wider clinical applications of 9p status in clear cell renal cell carcinoma (ccRCC) are limited owing to the lack of validation and consensus for interphase fluorescent in situ hybridisation (I-FISH) scoring technique. The aim of this study was to analytically validate the applicability of I-FISH in assessing 9p deletion in ccRCC and to clinically assess its long-term prognostic impact following surgical excision of ccRCC. METHODS: Tissue microarrays were constructed from 108 renal cell carcinoma (RCC) tumour paraffin blocks. Interphase fluorescent in situ hybridisation analysis was undertaken based on preset criteria by two independent observers to assess interobserver variability. 9p status in ccRCC tumours was determined and correlated to clinicopathological variables, recurrence-free survival and disease-specific survival. RESULTS: There were 80 ccRCCs with valid 9p scoring and a median follow-up of 95 months. Kappa statistic for interobserver variability was 0.71 (good agreement). 9p deletion was detected in 44% of ccRCCs. 9p loss was associated with higher stage, larger tumours, necrosis, microvascular and renal vein invasion, and higher SSIGN (stage, size, grade and necrosis) score. Patients with 9p-deleted ccRCC were at a higher risk of recurrence (P=0.008) and RCC-specific mortality (P=0.001). On multivariate analysis, 9p deletion was an independent predictor of recurrence (hazard ratio 4.323; P=0.021) and RCC-specific mortality (hazard ratio 4.603; P=0.007). The predictive accuracy of SSIGN score improved from 87.7% to 93.1% by integrating 9p status to the model (P=0.001). CONCLUSIONS: Loss of 9p is associated with aggressive ccRCC and worse prognosis in patients following surgery. Our findings independently confirm the findings of previous reports relying on I-FISH to detect 9p (CDKN2A) deletion. Nature Publishing Group 2014-09-23 2014-08-19 /pmc/articles/PMC4183850/ /pubmed/25137021 http://dx.doi.org/10.1038/bjc.2014.420 Text en Copyright © 2014 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/3.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Molecular Diagnostics
El-Mokadem, I
Fitzpatrick, J
Bondad, J
Rauchhaus, P
Cunningham, J
Pratt, N
Fleming, S
Nabi, G
Chromosome 9p deletion in clear cell renal cell carcinoma predicts recurrence and survival following surgery
title Chromosome 9p deletion in clear cell renal cell carcinoma predicts recurrence and survival following surgery
title_full Chromosome 9p deletion in clear cell renal cell carcinoma predicts recurrence and survival following surgery
title_fullStr Chromosome 9p deletion in clear cell renal cell carcinoma predicts recurrence and survival following surgery
title_full_unstemmed Chromosome 9p deletion in clear cell renal cell carcinoma predicts recurrence and survival following surgery
title_short Chromosome 9p deletion in clear cell renal cell carcinoma predicts recurrence and survival following surgery
title_sort chromosome 9p deletion in clear cell renal cell carcinoma predicts recurrence and survival following surgery
topic Molecular Diagnostics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183850/
https://www.ncbi.nlm.nih.gov/pubmed/25137021
http://dx.doi.org/10.1038/bjc.2014.420
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