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.