Eosinophilic and classic chromophobe renal cell carcinomas have similar frequent losses of multiple chromosomes from among chromosomes 1, 2, 6, 10, and 17, and this pattern of genetic abnormality is not present in renal oncocytoma

Abstract

That chromophobe renal cell carcinoma has an uncommon eosinophilic variant has been recognized for more than a decade. In sections stained with hematoxylin and eosin, the eosinophilic variant of chromophobe renal cell carcinoma and renal oncocytoma are similar in appearance. While it is well established that chromophobe renal cell carcinoma and renal oncocytoma have different patterns of genetic anomalies, little is known of the genetics of the eosinophilic variant of chromophobe renal cell carcinoma. This study was undertaken to elucidate the genetic lesions of eosinophilic chromophobe renal cell carcinoma and to compare them with those found in classic chromophobe renal cell carcinoma and in renal oncocytoma. A total of 29 renal neoplasms-nine eosinophilic chromophobe renal cell carcinomas, 10 classic chromophobe renal cell carcinomas, and 10 oncocytomas-were investigated by fluorescence in situ hybridization on 5 lm paraffinembedded tissue sections with centromeric probes for chromosomes 1, 2, 6, 10, and 17. Signals were counted in 100-200 neoplastic nuclei from each tumor. Chromophobe renal cell carcinomas frequently showed loss of chromosomes 1 (70% of classic, 67% of eosinophilic), 2 (90% classic, 56% eosinophilic), 6 (80% classic, 56% eosinophilic), 10 (60% classic, 44% eosinophilic), and 17 (90% classic, 78% eosinophilic); Among the classic chromophobe renal cell carcinomas, only one had no loss of any of the chromosomes, while 50% had loss of all five chromosomes. Among the eosinophilic chromophobe renal cell carcinomas, one of nine had no loss and 44% had loss of all five chromosomes. One oncocytoma had loss of chromosome 1. No other chromosomal loss was detected in the oncocytomas. In conclusion, losses of chromosomes 1, 2, 6, 10, and 17 are frequent in both eosinophilic and classic chromophobe renal cell carcinomas. Loss of chromosome 1 occurs occasionally in oncocytoma but losses of chromosomes 2, 6, 10, and 17 are not found in oncocytomas. When the differential diagnostic problem is oncocytoma vs eosinophilic chromophobe renal cell carcinoma, detection of losses of chromosomes 2, 6, 10, or 17 effectively excludes the diagnosis of oncocytoma and supports the diagnosis of chromophobe renal cell carcinoma.

Interphase cytogenetic analysis with centromeric probes for chromosomes 1, 2, 6, 10, and 17 in 11 tumors from a patient with bilateral renal oncocytosis

“…Thus, none of the three tumors showed loss of any of chromosomes 2, 6, 10, or 17. Since losses of one or more of these chromosomes are extremely common in chromophobe renal cell carcinomas, 10 the data from these three tumors offer little or no support for the hypothesis that the 'hybrid' tumors of renal oncocytosis are, in some way, intermediate between oncocytoma and chromophobe renal cell carcinoma. 'Hybrid' tumors are common in renal oncocytosis, whereas sporadic renal tumors with hybrid morphologic patterns are, at most, extremely rare, with only six having been reported, none with genetic analysis.…”

“…10 Reports of genetic analyses of renal oncocytosis are few. Leroy et al 7 reported a normal karyotype in two tumors histologically resembling oncocytomas in a case of bilateral renal oncocytosis associated with renal failure.…”

“…19,20 Combining the data from Leroy et al, 7 Al-Saleem et al, 18 and the present study, 13 tumors resembling oncocytomas from cases of oncocytosis have had some genetic analysis, and loss of 1p demonstrated by microsatellite analysis in one tumor has been the only abnormality detected. A close relationship between renal oncocytoma and chromophobe renal cell carcinoma has been suggested, based on the theory of common origin of these lesions from the intercalated ducts of the distal nephron, the morphologic similarities between renal oncocytoma and the eosinophilic variant of chromophobe renal cell carcinoma, 10,21 and the coexistence of tumors resembling oncocytoma, chromophobe renal cell carcinoma, and the ones with features of both in the kidneys from patients with renal oncocytosis. 2,5,7 Since a minority of renal oncocytomas are known to have losses of chromosome 1, the information presently available about the genetics of the tumors resembling oncocytomas is compatible with their being identical to sporadic oncocytomas.…”

“…Fluorescence In Situ Hybridization Analysis FISH was performed as described previously [10][11][12][13][14][15][16][17] with centromeric a-satellite DNA probes for chromosome 1 (centromeric enumeration probe (CEP) 1, spectrum orange), chromosome 2 (CEP 2, spectrum orange), chromosome 6 (CEP 6, spectrum green), chromosome 10 (CEP 10, spectrum green), and chromosome 17 (CEP 17, spectrum orange) (Figure 2). All the probes were from Vysis (Vysis, Downers Grove, IL, USA).…”

“…Since chromophobe carcinomas differ from oncocytomas in having multiple chromosomal losses, the identification of specific chromosomal losses is an additional tool for distinguishing these tumors. 10 We undertook to analyze 11 tumors from a patient with bilateral renal oncocytosis using fluorescence in situ hybridization (FISH) with centromeric probes for the chromosomes most frequently lost in chromophobe renal cell carcinomas (chromosomes 1, 2, 6, 10, and 17) to test the hypothesis that the tumors of renal oncocytosis are related to chromophobe renal cell carcinoma.…”