Chromosome 9p deletion in clear cell renal cell carcinoma predicts recurrence and survival following surgery.
Chromosome 9p deletion in clear cell renal cell carcinoma predicts recurrence and survival following surgery.
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DOI：
10.1038/bjc.2014.420
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发表时间：
2014-09-23
影响因子：
8.8
通讯作者：
Nabi, G.
中科院分区：
文献类型：
--
作者：
El-Mokadem, I.;Fitzpatrick, J.;Bondad, J.;Rauchhaus, P.;Cunningham, J.;Pratt, N.;Fleming, S.;Nabi, G.
关键词：
由于间期荧光原位杂交（I-FISH）评分技术缺乏验证和共识，9 p状态在肾透明细胞癌（ccRCC）中的广泛临床应用受到限制。本研究的目的是分析验证I-FISH在评估ccRCC中9 p缺失的适用性，并在临床上评估手术切除ccRCC后其长期预后影响。从108个肾细胞癌（RCC）肿瘤石蜡块构建组织微阵列。间期荧光原位杂交分析进行了两个独立的观察员，以评估观察员间的变异性的基础上预设的标准。ccRCC肿瘤中的9 p状态被确定并与临床病理变量、无复发生存期和疾病特异性生存期相关。有80例ccRCC具有有效的9 p评分，中位随访时间为95个月。观察者间变异性的Kappa统计量为0.71（一致性良好）。在44%的ccRCC中检测到9 p缺失。9 p丢失与更高的分期、更大的肿瘤、坏死、微血管和肾静脉浸润以及更高的SSIGN（分期、大小、分级和坏死）评分相关。9 p缺失ccRCC患者的复发风险（P=0.008）和RCC特异性死亡率（P=0.001）较高。多变量分析显示，9 p缺失是复发（风险比4.323; P=0.021）和RCC特异性死亡率（风险比4.603; P=0.007）的独立预测因子。通过将9 p状态整合到模型中，SSGN评分的预测准确性从87.7%提高到93.1%（P=0.001）。9 p缺失与手术后患者的侵袭性ccRCC和更差的预后相关。我们的研究结果独立地证实了先前报道的依赖于I-FISH检测9 p（CDKN 2A）缺失的结果。
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. 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. 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). 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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