Human chromophobe cell renal carcinoma

Chromophobe renal cell carcinoma (RCC) is a form of renal cancer that may be confused with other eosinophilic renal tumors, including oncocytoma, type 2 papillary RCC, and clear-cell RCC with eosinophilic features. There are currently no robust markers to distinguish these neoplasms. Chromophobe RCC and renal oncocytoma are presumably derived from the distal nephron. FXYD2 is a distal tubule regulator of the trimeric Na þ / K þ -transporting ATPase that is enriched in kidney tissue. In this study, we investigated the expression of FXYD2 in normal human kidney, 27 chromophobe RCCs, 30 oncocytomas, 15 clear-cell RCCs, and 11 papillary RCCs. Immunohistochemical staining for FXYD2 showed diffuse, strong immunoreactivity in the basolateral membrane of distal tubules of normal human kidney. Ninety-six percent (26/27) of chromophobe RCCs were immunoreactive for FXYD2 in a distinctly membranous pattern. Twenty-five of these tumors showed at least focal 2 þ staining. In contrast, only 17% (5/30) of renal oncocytomas, 11% (2/15) of clear-cell RCCs, and 0% (0/11) of papillary RCCs displayed FXYD2 immunoreactivity. None of these cases showed Z2 þ FXYD2 staining. A subset of cases was confirmed as oncocytoma or chromophobe RCC using cytokeratin 7, colloidal iron, and interphase fluorescence in situ hybridization analysis of chromosomes 1, 2, 6, 10, and 17. Among this subset, 100% (7/7) of chromophobe RCCs were FXYD2 positive, whereas 17% (2/12) of oncocytomas were stained with FXYD2. The oncocytomas that stained with FXYD2 did so in a weak (1 þ ), patchy manner. In contrast, chromophobe RCCs showed Z2 þ staining in 86% (6/7) of these tumors. For comparison, this subset was also stained for kidney-specific cadherin (Ksp-cadherin). Ksp-cadherin showed positive staining in 100% (7/7) of chromophobe RCCs and 33% (4/12) of oncocytomas. This is the first report demonstrating the potential utility of FXYD2 immunohistochemistry in the diagnosis of chromophobe RCC.

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“…[9][10][11][12][13][14] However, none of these modalities has thus far proven to be ideal. Therefore, more robust markers are still needed.…”

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Expression of the Na+/K+-transporting ATPase gamma subunit FXYD2 in renal tumors

et al. 2013

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“…While chromophobe renal cell carcinoma was first recognized as a distinct type of renal cell carcinoma in 1985 1 and was given its name because the cytoplasm of the cells was pale, in 1988 Thoenes et al 2 recognized that it has an eosinophilic variant. Cells with eosinophilic cytoplasm commonly are present in classic chromophobe renal cell carcinomas and the designation of the eosinophilic variant has been reserved for tumors composed either exclusively or predominantly of cells with eosinophilic cytoplasm.…”

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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

et al. 2005

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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.

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“…Several features have been proposed to accurately recognize chromophobe carcinoma, includ-ing histochemical, immunohistochemical, genetic, and ultrastructural findings (4,(7)(8)(9)(10)(11)(12)(13)(14). In particular, chromophobe renal carcinoma is characteristically stained by Hale's colloidal iron (10,12), immunoreacts with anti-E-cadherin (14) and antimitochondrial 113-1 (11) antibodies, and shows hypodiploidy caused by frequent loss of many different chromosomes (8,9).…”

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Parvalbumin Is Constantly Expressed in Chromophobe Renal Carcinoma

et al. 2001

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Chromophobe renal carcinoma is composed of neoplastic cell showing several features similar to those found in the intercalated cells of the collecting ducts. Because the distal nephron expresses calcium-binding proteins playing a role in calcium homeostasis, we reasoned that these proteins could be expressed by chromophobe carcinoma and therefore represent a diagnostic marker. We studied the immunohistochemical expression of different calcium-binding proteins (parvalbumin, calbindin-D28K, and calretinin) in 140 renal tumors, including 75 conventional (clear cell) carcinomas, 32 chromophobe carcinomas, 17 papillary renal cell carcinomas, and 16 oncocytomas. Parvalbumin was strongly positive in all primary chromophobe carcinomas and in one pancreatic metastasis; it was positive in 11 of 16 oncocytomas and absent in conventional (clear cell) and papillary renal cell carcinomas, either primary or metastatic. Calbindin-D28K and calretinin were negative in all tumors, with the exception of two chromophobe carcinomas, four oncocytomas, and two papillary renal cell carcinomas showing inconspicuous calretinin expression. Our data demonstrate that parvalbumin may be a suitable marker for distinguishing primary and metastatic chromophobe carcinoma from conventional (clear cell) and papillary renal cell carcinoma. Moreover, they suggest a relationship between chromophobe renal carcinoma and renal oncocytoma and indicate that chromophobe carcinoma exhibits differentiation toward the collectingduct phenotype.

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Human chromophobe cell renal carcinoma

Cited by 325 publications

References 6 publications

Expression of the Na+/K+-transporting ATPase gamma subunit FXYD2 in renal tumors

Expression of the Na+/K+-transporting ATPase gamma subunit FXYD2 in renal tumors

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

Parvalbumin Is Constantly Expressed in Chromophobe Renal Carcinoma

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