Expression of Alpha-Methylacyl-CoA Racemase in Papillary Renal Cell Carcinoma

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Abstract
Alpha-methylacyl-CoA racemase (AMACR) was first discovered by using cDNA microarray technology as a molecular marker for prostate cancer. Our recent microarray analysis of renal cell carcinomas showed a significant increase of AMACR mRNA levels in papillary renal cell carcinomas, but not in other subtypes. To investigate the value of this marker in pathologic diagnosis, we analyzed AMACR mRNA levels in cDNA microarrays from 70 kidney tumors. Furthermore, we evaluated the AMACR expression in 165 kidney tumors on tissue microarrays and 51 papillary carcinomas of other organs by immunohistochemistry. AMACR mRNA was significantly overexpressed in 7 of 8 papillary renal cell carcinomas with an average of 5.2-fold increase, and only in 2 of 62 nonpapillary kidney tumors. Immunohistochemistry demonstrated strong AMACR positivity in all cases of papillary renal cell carcinomas (41 of 41, 100%), including 6 metastatic papillary renal cell carcinomas, but only focal or weak reactivity in the minority (18 of 124, 15%) of other renal tumors including 13 of 52 clear cell renal cell carcinomas, 3 of 20 oncocytomas, and 2 of 17 urothelial carcinomas. All chromophobe (0 of 18) and sarcomatoid components of renal cell carcinomas (0 of 15) were negative for AMACR. Weak or focal AMACR immunoreactivity was detected in only 4 of 51 (8%) papillary carcinomas arising in other organs (2 of 14 thyroid, 2 of 13 lung, 0 of 6 breast, 0 of 6 endometrium, 0 of 6 ovary, and 0 of 6 pancreas). Using a combination of cDNA microarrays, tissue microarrays, and immunohistochemistry, we identified AMACR as a marker for papillary renal cell carcinoma, which could be valuable in subclassification of renal cell carcinomas and in the differential diagnosis of a metastatic papillary carcinoma.