Chromophobe renal cell carcinoma—chromosomal aberration variability and its relation to Paner grading system: an array CGH and FISH analysis of 37 cases

Abstract

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.

Low‐grade oncocytic tumour of kidney (CD117‐negative, cytokeratin 7‐positive): a distinct entity?

“…In their study, one of the most comprehensive ever undertaken on ChrRCC, the remaining 62 of 66 ChrRCC cases (which also included 19 eosinophilic ChrRCC), demonstrated a classic karyotype profile of ChrRCC, with frequent multiple losses of chromosomes 1, 2, 6, 10, 13 and 17 (in 86% of cases) and less common losses of chromosomes 3, 5, 8, 9, 11, 18 and 21 (in 12–58% of cases). In some studies, however, a combination of chromosomal losses and gains have been found in usual ChrRCC . To our knowledge, the only other study that included similar tumours to the LOT described herein was conducted by Kuroda et al .…”

Mucinous spindle and tubular renal cell carcinoma: analysis of chromosomal aberration pattern of low-grade, high-grade, and overlapping morphologic variant with papillary renal cell carcinoma

“…Renal tumors characterized by multiple losses are traditionally designated as chromophobe RCC, with losses frequently involving chromosomes 1, 2, 6, 10, 13, 17, and 21 [1]. However, recent studies have revealed a wider spectrum of chromosomal abnormalities including not only multiple losses but also numerous gains [11,18,19]. From the genetic point of view, one may speculate the existence of a histogenetic link between MTSRCC and CHRCC.…”

“…The procedures of DNA purification, integrity control, array CGH, and fluorescent in situ hybridization (FISH) analysis were described previously [11]. Required integrity of DNA was 400 base pairs.…”

Chromophobe renal cell carcinoma with neuroendocrine and neuroendocrine-like features. Morphologic, immunohistochemical, ultrastructural, and array comparative genomic hybridization analysis of 18 cases and review of the literature

“…However, recent articles in which larger cohorts of cases were analyzed have described a more variable genetic pattern with multiple losses as well as with multiple gains. In these studies, chromosomal gains were most frequently detected on chromosomes 4, 7, 15, 19, and 20 [8,26,27]. These findings indicate that the molecular-genetic abnormalities in CRCC can encompass a considerably broader spectrum than was previously suggested.…”

“…Each slide was independently enumerated by 2 observers (PM and PG). The cut-off values used for each probe were established in a previous study [8].…”