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

I. El-Mokadem; J. Fitzpatrick; J. Bondad; P. Rauchhaus; J. Cunningham; N. Pratt; S. Fleming; G. Nabi

doi:10.1038/bjc.2014.420

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

I. El-Mokadem (Lead / Corresponding author), J. Fitzpatrick, J. Bondad, P. Rauchhaus, J. Cunningham, N. Pratt, S. Fleming, G. Nabi

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Abstract

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.British Journal of Cancer advance online publication, 19 August 2014; doi:10.1038/bjc.2014.420 www.bjcancer.com.

Original language	English
Pages (from-to)	1381-1390
Number of pages	10
Journal	British Journal of Cancer
Volume	111
Issue number	7
Early online date	19 Aug 2014
DOIs	https://doi.org/10.1038/bjc.2014.420
Publication status	Published - 23 Sept 2014

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Fleming, Stewart
Person
Nabi, Ghulam
- Cancer Research - Clinical Professor (Teaching and Research) of Surgical Uro-Oncology
Person: Academic

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@article{a5f4f7448f9c4ce4a0bba751336747f2,

title = "Chromosome 9p deletion in clear cell renal cell carcinoma predicts recurrence and survival following surgery",

abstract = "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.British Journal of Cancer advance online publication, 19 August 2014; doi:10.1038/bjc.2014.420 www.bjcancer.com.",

author = "I. El-Mokadem and J. Fitzpatrick and J. Bondad and P. Rauchhaus and J. Cunningham and N. Pratt and S. Fleming and G. Nabi",

year = "2014",

month = sep,

day = "23",

doi = "10.1038/bjc.2014.420",

language = "English",

volume = "111",

pages = "1381--1390",

journal = "British Journal of Cancer",

issn = "0007-0920",

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TY - JOUR

T1 - Chromosome 9p deletion in clear cell renal cell carcinoma predicts recurrence and survival following surgery

AU - El-Mokadem, I.

AU - Fitzpatrick, J.

AU - Bondad, J.

AU - Rauchhaus, P.

AU - Cunningham, J.

AU - Pratt, N.

AU - Fleming, S.

AU - Nabi, G.

PY - 2014/9/23

Y1 - 2014/9/23

N2 - 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.British Journal of Cancer advance online publication, 19 August 2014; doi:10.1038/bjc.2014.420 www.bjcancer.com.

AB - 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.British Journal of Cancer advance online publication, 19 August 2014; doi:10.1038/bjc.2014.420 www.bjcancer.com.

U2 - 10.1038/bjc.2014.420

DO - 10.1038/bjc.2014.420

M3 - Article

C2 - 25137021

SN - 0007-0920

VL - 111

SP - 1381

EP - 1390

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 7

ER -

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

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Fleming, Stewart

Nabi, Ghulam

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