Alpha-methylacyl-CoA Racemase/P504S Overexpression in Colorectal Carcinoma is Correlated With Tumor Differentiation

Abstract

Alpha-methylacyl-CoA racemase (AMACR)/P504S is an enzyme involved in the metabolism of branched-chain fatty acids. Little is known about correlation of AMACR expression with colorectal carcinoma (CRC) differentiation and prognosis. We investigated the expression of AMACR in 106 cases of primary CRC, and in 47 lymph nodes with metastatic CRC by immunohistochemical analysis. These cases were divided into 3 groups according to the histologic differentiation of the primary tumors. group A included 50 cases of histologically well and moderately differentiated CRCs, 20 of these with lymph node metastasis; group B included 23 cases of well and moderately differentiated CRCs, histologically similar to group A, except these tumors had small foci (less than 20%) of high-grade carcinoma, and 10 of these had lymph node metastasis; group C included 33 cases of poorly differentiated adenocarcinoma and undifferentiated carcinoma, 17 with lymph node metastasis. The results showed the overall positive rates of expression in primary and metastatic CRCs were 59.4% and 46.8%, respectively. Expression in groups A (76.0%) and B (69.6%) was much higher than that in group C (27.3%). In group B, although overexpression of AMACR in primary tumors was similar to that of group A, it was only seen in 30.0% of group B metastatic tumors, which was similar to the rate of expression in group C (23.5%). In contrast, rates of expression in group A primary and metastatic tumors were similar (80.0% and 75.0%). Positive staining for AMACR in benign epithelium adjacent to tumor was rare (<2%). No relation was found between AMACR expression and overall survival. Our findings support the view that the expression of AMACR in CRC is correlated with tumor differentiation.

AMACR expression in colorectal cancer is associated with left-sided tumor localization

“…Other investigators described 45% to 83% AMACR positive CRC, but all of these studies were performed on patient numbers smaller than 200 [2,8,13,20,25,27,30]. The association found with non-mucinous tumor type, tumor grade, and tumor stage was also in line with the results of a previous study [13].…”

“…Comparable to Shi et al, no significant association between AMACR expression and prognosis could be found in our study, despite other features such as tumor grade and tumor stage which were highly significant for the outcome in this patient cohort [25]. However, the differences in AMACR expression between tumors of different grade and stage were quite small in terms of absolute numbers.…”

“…Several studies have shown that increased AMACR protein levels can be found in about 45-83% of colorectal carcinomas [2,8,13,20,25,27,30]. It was recently suggested that AMACR over-expression may be associated with favorable histological grade and good prognosis in colorectal cancer (CRC) [2,13,25,30].…”

“…It was recently suggested that AMACR over-expression may be associated with favorable histological grade and good prognosis in colorectal cancer (CRC) [2,13,25,30]. Chen et al have further suggested, that AMACR protein may serve as a tool to distinguish CRC from cancers derived from the small intestine [2].…”

Interpretation of needle biopsies of the kidney for investigation of renal masses

“…and immunohistochemical expression of classic renal markers (Table 6). It is of importance to stress that AMACR has no specificity for renal primaries and it is expressed in many adenocarcinomas of other origins, for example prostatic, gastric, or colorectal [41,42]. The most common primary sites are lung, breast, skin a b c Fig.…”