Douglass E C, Look A T, Webber B, Parham D, Wilimas J A, Green A A, Roberson P K
J Clin Oncol. 1986 Jun;4(6):975-81. doi: 10.1200/JCO.1986.4.6.975.
Flow cytometric measurement of the DNA content of Wilms' tumor cells revealed a striking correspondence with the histologic subtype and treatment outcome. In the 48 cases studied, a hyperdiploid DNA content ranging from 1.7 to 3.2 times the result for normal diploid cells distinguished all but one of the ten anaplastic tumors. Lower values, from 1.0 to 1.4 times the diploid DNA content, characterized the nonanaplastic specimens. By Kaplan-Meier analysis, the probability of achieving 3 years of relapse-free survival was significantly lower in the group with higher DNA content (0.42 v 0.87, P less than .01). Analysis of banded chromosomes for a subset of 22 patients contributed important information beyond the flow cytometric study. Cases of anaplasia associated with poorer responses to therapy showed numerous complex translocations, whereas all others lacked such changes. By combining flow cytometric techniques and conventional methods of chromosome analysis, it should be possible to identify those patients with Wilms' tumor who are most likely to fail therapy. The biologic implication of these findings is that the development of clinical drug resistance in Wilms' tumor is a result of the genetic instability of the malignant clone.
对肾母细胞瘤细胞的DNA含量进行流式细胞术测量，结果显示其与组织学亚型及治疗结果有着显著的对应关系。在所研究的48例病例中，超二倍体DNA含量为正常二倍体细胞结果的1.7至3.2倍，除1例间变性肿瘤外，其余9例间变性肿瘤均有此特征。非间变性标本的DNA含量较低，为二倍体DNA含量的1.0至1.4倍。通过Kaplan-Meier分析，DNA含量较高组实现3年无复发生存的概率显著较低（0.42对0.87，P小于0.01）。对22例患者的一个子集进行带型染色体分析，得出了超出流式细胞术研究的重要信息。与治疗反应较差相关的间变病例显示出大量复杂易位，而其他所有病例均无此类变化。通过结合流式细胞术技术和传统染色体分析方法，应该能够识别出那些最有可能治疗失败的肾母细胞瘤患者。这些发现的生物学意义在于，肾母细胞瘤临床耐药性的产生是恶性克隆基因不稳定的结果。
