Messenger RNA Expression Ratios among Four Genes Predict Subtypes of Renal Cell Carcinoma and Distinguish Oncocytoma from Carcinoma

Abstract

Purpose: Morphologic distinction among clear cell, papillary, and chromophobe types of renal cell carcinoma (RCC) can be difficult, as is the differential diagnosis between oncocytoma and RCC.Whether these renal tumors can be distinguished by their mRNA expression profile of a few selected genes was examined. Experimental Design:The expression of four genes in renal tumor was evaluated by quantitative reverse transcription-PCR: carbonic anhydrase IX (CA9), methylacyl-CoA racemase (AMACR), parvalbumin (PVALB), and chloride channel kb (CLCNKB). Thirty-one fresh-frozen and 63 formalin-fixed, paraffin-embedded tumor specimens were analyzed. Results: CA9 expression was highest in clear cell carcinoma and lowest in chromophobe RCC and in oncocytoma. AMACR expression was highest in papillary RCC, and CLCNKB was highest in chromophobe RCC/oncocytoma. PVALB was highest in chromophobe RCC, variable in oncocytoma, and low in clear cell and papillary types. Similar findings were observed in fresh-frozen and formalin-fixed specimens. The mRNA expression ratios among these genes (i.e., CA9/ AMACR and AMACR/CLCNKB ratios) further accentuate the gene expression differences among these tumors, and a molecular diagnostic algorithm was established. This algorithm accurately classified the 31fresh-frozen tumors into 14 clear cell, 5 papillary, 6 chromophobe, and 6 oncocytomas. In the formalin-fixed group, the molecular criteria accurately classified the cases into 15 clear cell, 16 papillary, and 32 in the chromophobe/oncocytoma group but could only separate some, but not all, oncocytomas from chromophobe RCC. Conclusions: RNA expression ratios based on the four-gene panel can accurately classify subtypes of RCC as well as help distinguish some oncocytomas from chromophobe RCC.Renal cell carcinomas (RCC) are classified histologically into conventional clear cell, papillary, and chromophobe types (1). Clear cell type is by far the most common, accounting for 70% to 80% of the RCC. In comparison, 10% to 15% of the RCC are of the papillary type and f5% are of the chromophobe type (2). The distinction of these different types is clinically important, as papillary and chromophobe types have a better prognosis than the clear cell type (3). For instance, Thoenes et al. (4) reported a 5-year overall survival rate of 92% for chromophobe in contrast to 62% for clear cell type. Similarly, a 5-year survival rate of 82% to 90% has also been reported for papillary renal carcinoma (5, 6).Although the histologic diagnosis of these different subtypes of RCC can be made unequivocally in most cases, selected cases can be difficult, particularly the chromophobe type. Moreover, the differential diagnosis between RCC and renal oncocytoma can pose a diagnostic dilemma. Oncocytoma, comprising 3% to 5% of the renal tumors, is generally considered a benign neoplasm (7). However, some cases of oncocytoma can show atypical histologic features, leading to their being interpreted as RCC, either as chromophobe type or as RCC, unclassified, for fear of u...

The PTEN regulator DJ‐1 is associated with hTERT expression in clear cell renal cell carcinoma

“…1 Phenotypic differences between ccRCC and pRCC have also been shown from several laboratories including ours. [44][45][46][47] Furthermore, in pRCC, both the cMyc and hTERT genes were upregulated in comparison with normal tissue, but no association between cMyc and hTERT was found. This suggests that the putative cMyc-hTERT axis shown in ccRCC is not functioning in pRCC, besides the fact that DJ-1 seemed to be of no importance for hTERT expression levels in pRCC.…”

Localization of a Prostate Cancer Predisposition Gene to an 880-kb Region on Chromosome 22q12.3 in Utah High-Risk Pedigrees

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Gene Expression Profiling Separates Chromophobe Renal Cell Carcinoma from Oncocytoma and Identifies Vesicular Transport and Cell Junction Proteins as Differentially Expressed Genes

“…Conventional and quantitative reverse transcription-PCR (RT-PCR) were done as described (25). Conventional RT-PCR was done with 30 amplification cycles to emulate a semiquantitative assay, whereas quantitative RT-PCR assays were run for 45 cycles.…”