Department of Pathology, Faculty of Medicine in Plzen, Charles University in Prague, Pilsen, Czech Republic.
Department of Pathology, University of Erlangen, Erlangen, Germany.
Histopathology. 2019 Jul;75(1):104-117. doi: 10.1111/his.13856.
Primary renal well-differentiated neuroendocrine tumour (NET) (hereafter referred to as renal NET) is rare, with ~100 cases having been reported in the literature. There are also limited data on the molecular-genetic background of primary renal NETs.
We analysed 11 renal NETs by using next-generation sequencing (NGS) to identify characteristic genetic aberrations. All tumours were positive for synaptophysin, and also expressed insulinoma-associated protein 1 (10/11), chromogranin-A (8/11), and CD56 (3/11). Cytoplasmic positivity of CD99 was present in eight of 11 cases, and strong nuclear expression of α-thalassaemia/mental retardation syndrome X-linked (ATRX) was retained in all 11 cases. Molecular-genetic analysis of aberration of VHL gave negative results in all cases. Loss of heterozygosity on chromosome 3p21 was found in three of nine analysable cases. NGS was successful in nine cases, showing a total of 56 variants being left after the updated filtering process, representing an average of five variants per sample. All analysable cases were negative for ATRX and DAXX (death-domain associated protein X) mutations. The most frequently mutated genes were CDH1 and TET2, with three mutations in two cases. Mutations in AKT3, ROS1, PIK3R2, BCR and MYC were found in two cases. The remaining 41 genes were found to be mutated only in individual cases. In four cases, the mutations affected a subset of genes related to angiogenesis.
Overall, the mutation profile of primary renal NETs is variable, and none of the studied genes or affected pathways seems to be specific for renal NET.
原发性肾脏分化良好的神经内分泌肿瘤（NET）（以下简称肾 NET）较为罕见，文献中报道的病例约有 100 例。关于原发性肾 NET 的分子遗传学背景也仅有有限的数据。
我们通过下一代测序（NGS）分析了 11 例肾 NET，以鉴定特征性的遗传异常。所有肿瘤均突触素阳性，同时还表达胰岛素瘤相关蛋白 1（10/11）、嗜铬粒蛋白 A（8/11）和 CD56（3/11）。11 例中有 8 例 CD99 细胞质阳性，11 例均保留α-地中海贫血/智力低下综合征 X 连锁（ATRX）的强核表达。所有病例的 VHL 错配分析结果均为阴性。在 9 例可分析的病例中，有 3 例发现 3p21 染色体杂合性缺失。9 例中有 8 例 NGS 成功，经过更新的过滤过程后，总共留下 56 个变体，每个样本平均有 5 个变体。所有可分析的病例均为 ATRX 和 DAXX（死亡域相关蛋白 X）突变阴性。最常突变的基因是 CDH1 和 TET2，有 2 例各有 3 个突变。AKT3、ROS1、PIK3R2、BCR 和 MYC 的突变在 2 例中发现。其余 41 个基因仅在个别病例中发生突变。在 4 例中，突变影响了一组与血管生成相关的基因。
总体而言，原发性肾 NET 的突变谱是多变的，没有研究的基因或受影响的途径似乎是肾 NET 所特有的。
