Institute of Urologic Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Eur Urol. 2012 May;61(5):888-95. doi: 10.1016/j.eururo.2012.01.012. Epub 2012 Jan 18.
While it is well known that clear cell renal cell carcinoma (ccRCC) that presents with lymphatic spread is associated with an extremely poor prognosis, its molecular and genetic biology is poorly understood.
Define the clinicopathologic, molecular, and genetic biological characteristics of these tumors in comparison to nonmetastatic (N0M0) renal cell carcinomas.
DESIGN, SETTING, AND PARTICIPANTS: A retrospective study defined clinicopathologic features, expression of 28 molecular markers, and occurrence of chromosomal aberrations for their correlation with lymphatic spread in three cohorts of 502, 196, and 272 patients, respectively.
Fisher exact test or the χ(2) test were used to compare categorical variables; continuous variables were compared with the Mann-Whitney U test or student t test. Cut-off values were calculated based on receiver operating characteristic curves and the Youden Index. Uni- and multivariate regression analyses were used to investigate the correlation with lymphatic spread.
In clinical analyses, a predictive model consisting of smoking history (p=0.040), T stage (p<0.0001), Fuhrman grade (p<0.0001), Eastern Cooperative Oncology Group performance status (p<0.0001), and microvascular invasion (p<0.0001) was independently associated with lymphatic spread. After adjustment with these clinical variables, low carbonic anhydrase IX (CAIX) (p=0.043) and high epithelial vascular endothelial growth factor receptor 2 (p=0.033) protein expression were associated with a higher risk of lymphatic spread, and loss of chromosome 3p (p<0.0001) with a lower risk. The current study is limited by its retrospective design, small sample size, and single-center experience.
The low rates of CAIX expression and loss of chromosome 3p suggest that lymphatic spread in ccRCC occurs independently of von Hippel-Lindau tumor suppressor inactivation.
虽然众所周知，伴有淋巴转移的透明细胞肾细胞癌（ccRCC）预后极差，但对其分子和遗传生物学知之甚少。
与无转移（N0M0）肾细胞癌相比，明确这些肿瘤的临床病理、分子和遗传生物学特征。
设计、设置和参与者：一项回顾性研究通过三个队列（分别为 502、196 和 272 例患者）定义了临床病理特征、28 种分子标志物的表达和染色体异常的发生情况，以确定它们与淋巴转移的相关性。
使用 Fisher 确切检验或 χ(2)检验比较分类变量；使用 Mann-Whitney U 检验或学生 t 检验比较连续变量。基于接收者操作特征曲线和 Youden 指数计算截断值。使用单变量和多变量回归分析来研究与淋巴转移的相关性。
在临床分析中，由吸烟史（p=0.040）、T 分期（p<0.0001）、Fuhrman 分级（p<0.0001）、东部肿瘤协作组体能状态（p<0.0001）和微血管侵犯（p<0.0001）组成的预测模型与淋巴转移独立相关。在调整这些临床变量后，碳酸酐酶 IX（CAIX）低（p=0.043）和上皮血管内皮生长因子受体 2 高（p=0.033）蛋白表达与更高的淋巴转移风险相关，而染色体 3p 缺失（p<0.0001）与更低的风险相关。本研究受到回顾性设计、样本量小和单中心经验的限制。
CAIX 表达降低和染色体 3p 缺失提示 ccRCC 中的淋巴转移独立于 von Hippel-Lindau 肿瘤抑制基因失活。
