Klatte Tobias, Rao P Nagesh, de Martino Michela, LaRochelle Jeffrey, Shuch Brian, Zomorodian Nazy, Said Jonathan, Kabbinavar Fairooz F, Belldegrun Arie S, Pantuck Allan J
Department of Urology, David Geffen School of Medicine at UCLA, Center for Health Sciences, Los Angeles, CA 90025-1738, USA.
J Clin Oncol. 2009 Feb 10;27(5):746-53. doi: 10.1200/JCO.2007.15.8345. Epub 2009 Jan 5.
The majority of cytogenetic studies in renal cell carcinoma (RCC) have been impaired by small sample size, retrospective character, and lack of a survival end point. We prospectively studied the prognostic impact of cytogenetic abnormalities on a larger cohort of patients having up to 108 months of follow-up.
Tumors of 282 patients who underwent nephrectomy for clear cell RCC were cytogenetically analyzed. Results were correlated with pathological factors and disease-specific survival.
The most frequently observed cytogenetic abnormalities were loss of 3p (60%), gain of 5q (33%), loss of 14q (28%), trisomy 7 (26%), loss of 8p (20%), loss of 6q (17%), loss of 9p (16%), loss of 4p (13%), and loss of chromosome Y in men (55%). Tumors with loss of 3p presented at lower TNM stages. Loss of 4p, 9p, and 14q were all associated with higher TNM stages, higher grade, and greater tumor size. A deletion of 3p was associated with better prognosis (P = .03), while loss of 4p (P < .001), loss of 9p (P < .01), and loss of 14q (P < .01) were each associated with worse prognosis. Loss of the Y chromosome led to improved progression-free survival in metastatic patients (P = .02). In multivariate analysis, loss of 9p was retained as an independent prognostic factor.
This cytogenetic study serves as a proof of principal that genetic information, such as loss of chromosome 9, can be obtained from widely available technology, and can provide additional prognostic information to standard clinicopathologic variables.
大多数肾细胞癌（RCC）的细胞遗传学研究因样本量小、回顾性特点以及缺乏生存终点而受到影响。我们前瞻性地研究了细胞遗传学异常对一大群患者的预后影响，这些患者的随访时间长达108个月。
对282例行肾切除术的透明细胞RCC患者的肿瘤进行细胞遗传学分析。结果与病理因素和疾病特异性生存相关。
最常观察到的细胞遗传学异常为3p缺失（60%）、5q增益（33%）、14q缺失（28%）、7号染色体三体（26%）、8p缺失（20%）、6q缺失（17%）、9p缺失（16%）、4p缺失（13%）以及男性Y染色体缺失（55%）。3p缺失的肿瘤处于较低的TNM分期。4p、9p和14q缺失均与较高的TNM分期、较高分级以及更大的肿瘤大小相关。3p缺失与较好的预后相关（P = 0.03），而4p缺失（P < 0.001）、9p缺失（P < 0.01）和14q缺失（P < 0.01）均与较差的预后相关。Y染色体缺失使转移性患者的无进展生存期得到改善（P = 0.02）。在多变量分析中，9p缺失被保留为独立的预后因素。
这项细胞遗传学研究证明了一个原理，即可以从广泛可用的技术中获取诸如9号染色体缺失等遗传信息，并且这些信息可以为标准的临床病理变量提供额外的预后信息。
