CD 9 and vimentin distinguish clear cell from chromophobe renal cell carcinoma

Abstract

Background: Clear cell renal cell carcinoma (ccRCC) and chromophobe renal cell carcinoma (chRCC) can usually be distinguished by histologic characteristics. Occasionally, diagnosis proves challenging and diagnostic difficulty will likely increase as needle biopsies of renal lesions become more common.

Methods: To identify markers that aid in differentiating ccRCC from chRCC, we used gene expression profiles to identify candidate markers that correlate with histology. 39 antisera and antibodies, including 35 for transcripts identified from gene expression profiling, were evaluated. Promising markers were tested on a tissue microarray (TMA) containing 428 renal neoplasms. Strength of staining of each core on the TMA was formally scored and the distribution of staining across different types of renal neoplasms was analyzed.

Results: Based on results from initial immunohistochemical staining of multitissue titer arrays, 23 of the antisera and antibodies were selected for staining of the TMA. For 7 of these markers, strength of staining of each core on the TMA was formally scored. Vimentin (positive in ccRCC) and CD9 (positive in chRCC) best distinguished ccRCC from chRCC. The combination of vimentin negativity and CD9 positivity was found to distinguish chRCC from ccRCC with a sensitivity of 100.0% and a specificity of 95.2%.

Conclusion: Based on gene expression analysis, we identify CD9 and vimentin as candidate markers for distinguishing between ccRCC and chRCC. In difficult cases and particularly when the amount of diagnostic tissue is limited, vimentin and CD9 staining could serve as a useful adjunct in the differential diagnosis of ccRCC and chRCC.

Figure 1

Gene expression profiling of 22 ccRCC and 9 chRCC. (A) Dendrogram of unsupervised hierarchical cluster analysis of the 31 samples with chRCC in red and subtypes I, II, III, IV, and V of ccRCC identified previously in orange, yellow, pink, blue and purple, respectively. (B) Dendrogram of supervised cluster analysis with list of genes identified by SAM procedure as being differentially expressed between ccRCC and chRCC. (C) Image of supervised cluster analysis with each row representing a single gene and each column a patient sample. The degree of color saturation corresponds to the ratio of gene expression in each sample compared to the mean expression across all samples. (D) Genes whose expression levels were determined using RCC TMA and for which scoring was performed. (E) Genes whose expression levels were determined using titering TMA or RCC TMA and for which scoring was not performed.

Figure 2

Representative ccRCC and chRCC cores on RCC TMA stained for vimentin and CD9.