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. 2014 Sep 23;111(7):1381-90.
doi: 10.1038/bjc.2014.420. Epub 2014 Aug 19.

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

I El-Mokadem  1 , J Fitzpatrick  1 , J Bondad  1 , P Rauchhaus  2 , J Cunningham  3 , N Pratt  3 , S Fleming  4 , G Nabi  1
Affiliations

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

I El-Mokadem et al. Br J Cancer. .

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.

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Figures

Figure 1
Figure 1
Algorithm for interphase FISH scoring of 9p deletion using the Vysis locus-specific identifier (LSI) CDKN2A spectrum red (R)/ chromosome 9 centromeric-enumeration probe (CEP9) spectrum green (G).
Figure 2
Figure 2
Agreed 9p status in tumour blocks by total number of cores scored.
Figure 3
Figure 3
Kaplan–Meier survival analysis. (A) RCC disease-specific survival (DSS) by 9p deletion status. (B) Recurrence-free survival (RFS) in localised RCC by 9p deletion status. (C) Disease-specific survival (DSS) in locally advanced non-metastatic RCC (pT3N0M0) by 9p deletion status.
See this image and copyright information in PMC

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