Neumann H P, Bender B U, Berger D P, Laubenberger J, Schultze-Seemann W, Wetterauer U, Ferstl F J, Herbst E W, Schwarzkopf G, Hes F J, Lips C J, Lamiell J M, Masek O, Riegler P, Mueller B, Glavac D, Brauch H
Department of Medicine, Albert-Ludwigs-Universität, Freiburg, Germany.
J Urol. 1998 Oct;160(4):1248-54.
Renal cell carcinoma occurs as a sporadic tumor but may be part of the autosomal dominant von Hippel-Lindau disease, characterized by retinal and central nervous system hemangioblastoma, pheochromocytoma, pancreatic cysts and renal cell carcinoma. We determine the prevalence of von Hippel-Lindau disease in a series of unselected renal cell carcinoma cases by molecular genetic analysis, and compare sporadic to von Hippel-Lindau renal cell carcinoma with respect to morphology and biology.
We established registers comprising 63 subjects with von Hippel-Lindau renal cell carcinoma, belonging to 30 distinct families (register A), and 460 unselected patients operated on for renal cell carcinoma in an 11-year period (register B). Molecular genetic analysis of the von Hippel-Lindau gene was performed for living patients of register A, representing 80% of von Hippel-Lindau families, and register B, 62% living patients, to identify von Hippel-Lindau germline mutations. In addition, register B was evaluated by a questionnaire (95% response) for familial occurrence of von Hippel-Lindau disease.
The prevalence of von Hippel-Lindau renal cell carcinoma was 1.6% in 189 consenting unselected renal cell carcinoma patients. Risk factors for occult germline von Hippel-Lindau gene mutations in register B included familial renal cell carcinoma in 3 of 3 patients (100%), multifocal or bilateral renal cell carcinoma in 1 of 10 (10%) and age younger than 50 years at diagnosis in 1 of 33 (3%). Compared to sporadic von Hippel-Lindau renal cell carcinoma was characterized by an occurrence 25 years earlier, association with renal cysts, multifocal and bilateral tumors, cystic organization and low grade histology, and a better 10-year survival (p < 0.001 each). In von Hippel-Lindau disease metastases occurred only in tumors larger than 7 cm.
von Hippel-Lindau differs from sporadic renal cell carcinoma in morphology and biology. Our data provide arguments for planning surgery for von Hippel-Lindau renal cell carcinoma and should stimulate future investigations.
肾细胞癌多为散发性肿瘤，但也可能是常染色体显性遗传性希佩尔-林道病的一部分，其特征为视网膜及中枢神经系统血管母细胞瘤、嗜铬细胞瘤、胰腺囊肿和肾细胞癌。我们通过分子遗传学分析确定一系列未经挑选的肾细胞癌病例中希佩尔-林道病的患病率，并比较散发性肾细胞癌与希佩尔-林道病相关性肾细胞癌的形态学和生物学特征。
我们建立了两个登记册，登记册A包含63例希佩尔-林道病相关性肾细胞癌患者，分属30个不同家庭；登记册B包含在11年期间接受肾细胞癌手术的460例未经挑选的患者。对登记册A中仍在世的患者（占希佩尔-林道病家庭的80%）以及登记册B中仍在世的患者（62%）进行了希佩尔-林道基因的分子遗传学分析，以识别希佩尔-林道病的种系突变。此外，通过问卷调查（回复率95%）对登记册B评估希佩尔-林道病的家族发病情况。
在189例同意参与研究的未经挑选的肾细胞癌患者中，希佩尔-林道病相关性肾细胞癌的患病率为1.6%。登记册B中隐匿性种系希佩尔-林道基因突变的风险因素包括：3例患者中有3例（100%）有家族性肾细胞癌病史、10例中有1例（10%）为多灶性或双侧性肾细胞癌、33例中有1例（3%）诊断时年龄小于50岁。与散发性肾细胞癌相比，希佩尔-林道病相关性肾细胞癌的发病时间早25年，与肾囊肿、多灶性和双侧性肿瘤、囊性结构及低级别组织学相关，且10年生存率更高（每项p<0.001）。在希佩尔-林道病中，转移仅发生在直径大于7 cm的肿瘤中。
希佩尔-林道病相关性肾细胞癌在形态学和生物学方面与散发性肾细胞癌不同。我们的数据为希佩尔-林道病相关性肾细胞癌的手术规划提供了依据，并应推动未来的研究。
