López José I, Angulo Javier C
Department of Pathology, Cruces University Hospital, Biocruces Research Institute, University of the Basque Country (UPV/EHU), 48903, Barakaldo, Spain.
Clinical Department, Urology, Hospital Universitario de Getafe, Universidad Europea de Madrid, 28905, Madrid, Spain.
Curr Urol Rep. 2018 Jan 27;19(1):3. doi: 10.1007/s11934-018-0754-7.
Intratumor heterogeneity is an inherent event in tumor development that is receiving much attention in the last years since it is responsible for most failures of current targeted therapies. The purpose of this review is to offer clinicians an updated insight of the multiple manifestations of a complex event that impacts significantly patient's life.
Clear cell renal cell carcinoma is the most common renal tumor and a paradigmatic example of a heterogeneous neoplasm. Next-generation sequencing has demonstrated that intratumor heterogeneity encompasses genetic, epigenetic, and microenvironmental variability. Currently accepted protocols of tumor sampling seem insufficient in unveiling intratumor heterogeneity with reliability and need to be updated. This variability challenges the precise morphological diagnosis, its molecular characterization, and the selection of optimal personalized therapies in clear cell renal cell carcinoma, a neoplasm traditionally considered chemo- and radio-resistant. We review the state of the art of the different approaches to intratumor heterogeneity in clear cell renal cell carcinomas, from the simple morphology to the most sophisticated massive sequencing tools.
肿瘤内异质性是肿瘤发生过程中的一个固有现象，近年来受到了广泛关注，因为它是导致当前大多数靶向治疗失败的主要原因。本综述旨在为临床医生提供关于这一复杂现象多种表现的最新见解，该现象对患者生活有重大影响。
透明细胞肾细胞癌是最常见的肾肿瘤，也是异质性肿瘤的典型例子。二代测序表明，肿瘤内异质性包括基因、表观遗传和微环境的变异性。目前公认的肿瘤取样方案似乎不足以可靠地揭示肿瘤内异质性，需要更新。这种变异性对透明细胞肾细胞癌的精确形态学诊断、分子特征分析以及最佳个体化治疗方案的选择提出了挑战，透明细胞肾细胞癌传统上被认为对化疗和放疗耐药。我们综述了从简单形态学到最复杂的大规模测序工具等不同方法在透明细胞肾细胞癌肿瘤内异质性研究方面的现状。
