Department of Pathology, East University, Riga, Latvia.
Virchows Arch. 2013 Oct;463(4):563-73. doi: 10.1007/s00428-013-1457-6. Epub 2013 Aug 3.
Genetically, chromophobe renal cell carcinoma (ChRCC) is characterized by multiple chromosomal changes, especially losses. The most common losses include chromosomes 1, 2, 6, 10, 13, 17, and 21. The Fuhrman grading system lacks prognostic relevance for ChRCC, and recently, a new grading system for ChRCC was proposed by Paner. The objective of this study was to map the spectrum of chromosomal aberrations (extent and location) in a large cohort of ChRCCs and relate these findings to the Paner grading system (PGS). A large cohort of ChRCC was reviewed and graded according to the PGS. All the cases were reevaluated and separated into groups according to their PGS. The final study set was 37 patients. ChRCCs were divided into PG 1-3, sarcomatoid, and aggressive groups. "Aggressive ChRCCs" were designated cases with known metastatic activity, local recurrence, aggressive growth to the adjacent organs, or invasive growth into the renal sinus (with/without angioinvasion). Sarcomatoid tumors were divided into their epithelial and sarcomatoid component (further molecular genetic analyses were performed separately). Array comparative genome hybridization and/or fluorescence in situ hybridization analysis was applied to 42 samples from the 37 cases. Multiple losses, as well as gains, were detected in different chromosomes. Regardless of the PGS groups, the most frequently detected losses involved chromosomes 1 (27/37), 2 (26/37), 6 (23/37), 10 (26/37), 13 (19/37), and 17 (24/37). Loss of chromosome 21 was found in 12/37 cases. The most frequently detected gains were found on chromosomes 4 (22/37), 7 (24/37), 15 (20/37), 19 (22/37), and 20 (21/37). Cluster analysis showed that there is no relation between PGS and particular pattern of chromosomal changes (losses or gains) in ChRCCs. Conclusions are as follows: (1) ChRCCs showed a significantly broader spectrum of chromosomal aberrations than previously recognized. While previously published chromosomal losses were found in our cohort, gains of multiple chromosomes were also identified in a high percentage. The most frequently detected gains involved chromosomes 4, 7, 15, 19, and 20. (2) There is no relation between chromosomal numerical changes and Paner grading system.
从遗传学角度来看，嫌色细胞肾细胞癌（ChRCC）的特征是多种染色体改变，尤其是缺失。最常见的缺失包括染色体 1、2、6、10、13、17 和 21。Fuhrman 分级系统对 ChRCC 的预后没有相关性，最近 Paner 提出了一种新的 ChRCC 分级系统。本研究的目的是绘制大样本 ChRCC 染色体畸变（程度和位置）图谱，并将这些发现与 Paner 分级系统（PGS）相关联。对大量 ChRCC 进行了回顾性分析，并根据 PGS 进行了分级。所有病例均重新评估，并根据 PGS 进行分组。最终研究组为 37 例患者。ChRCC 分为 PG1-3、肉瘤样和侵袭性组。“侵袭性 ChRCC”是指具有已知转移活性、局部复发、侵袭性生长至相邻器官或侵袭性生长至肾窦（伴/不伴血管侵犯）的病例。肉瘤样肿瘤分为上皮和肉瘤样成分（进一步进行单独的分子遗传学分析）。对 37 例病例中的 42 个样本进行了比较基因组杂交和/或荧光原位杂交分析。在不同染色体上检测到多种缺失和增益。无论 PGS 分组如何，最常检测到的缺失涉及染色体 1（37/37）、2（37/37）、6（37/37）、10（37/37）、13（37/37）和 17（37/37）。12/37 例病例中发现染色体 21 缺失。最常检测到的增益发生在染色体 4（37/37）、7（37/37）、15（37/37）、19（37/37）和 20（37/37）上。聚类分析表明，PGS 与 ChRCC 中特定的染色体改变（缺失或增益）模式之间没有关系。结论如下：（1）ChRCC 表现出比以前认识到的更广泛的染色体异常谱。虽然在我们的队列中发现了先前报道的染色体缺失，但也在高比例中发现了多个染色体的增益。最常检测到的增益涉及染色体 4、7、15、19 和 20。（2）染色体数量变化与 Paner 分级系统之间没有关系。
