title: Differential expression of alpha-methylacyl-coenzyme A racemase in colorectal carcinoma bears clinical and pathologic significance.
abstract: alpha-methylacyl-coenzyme A racemase (AMACR) is a recently discovered biomarker that is shown to be overexpressed in some prostatic carcinomas and associated with prostatic cancer progression. Given that AMACR plays an important role in peroxisomal beta-oxidation of branched-chain fatty acids from red meat and dairy products, and that consumption of red meat may increase risk of developing colon cancer as suggested by epidemiological studies, it is plausible to explore the function of AMACR in colorectal carcinoma. A few previous studies have indeed observed overexpression of AMACR in 45% to 69% of the colorectal carcinomas. However, the clinical and pathologic characteristics of such AMACR expressers have not been investigated. In this study, the immunohistochemical expression pattern of AMACR of 163 patients with primary colorectal carcinoma treated primarily with surgical resection was analyzed and correlated with tumor pathologic features (tumor location, histologic type, grade, pathologic stage, lymph node and distant metastasis) and patient outcome (disease-specific survival). The results showed variable positive staining for AMACR in 123 (75%) of 163 tumors, and moderate to strong staining in 63 (39%) of 163. Lack of staining or low-intensity staining appeared to correlate significantly with mucinous histology (P < .001), poor tumor differentiation (P = .021), and presence of lymphovascular invasion (P = .032). Patients whose tumors showed lack of staining or low-intensity staining also had a significantly worse 5-year disease-specific survival (P < .012), as did patients whose tumors had lymphovascular invasion, or were of high American Joint Committee on Cancer (AJCC) stage. On multivariate analysis, AMACR staining and AJCC staging remained independent predictors for patient outcome. Thus, our data suggest that AMACR expression in colorectal carcinoma correlates with certain tumor pathologic characteristics (histologic type, differentiation, and lymphovascular invasion) and patient outcome. Additional confirmatory studies are needed to establish the significance of AMACR as a prognostic marker for colorectal carcinoma. Further investigation on interaction between AMACR and other known colorectal cancer development pathways may provide new insights on colorectal carcinogenesis.
authors: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors: Anne
authors: A
authors: Lin
authors: Martin R
authors: MR
authors: Weiser
authors: David S
authors: DS
authors: Klimstra
authors: Philip B
authors: PB
authors: Paty
authors: Laura H
authors: LH
authors: Tang
authors: Hikmat
authors: H
authors: Al-Ahmadie
authors: Sun
authors: S
authors: Hoo Park
authors: Jose G
authors: JG
authors: Guillem
authors: Larissa
authors: L
authors: Temple
authors: W Douglas
authors: WD
authors: Wong
authors: William L
authors: WL
authors: Gerald
authors: Jinru
authors: J
authors: Shia
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019998:Racemases and Epimerases / Q000096:biosynthesis*; D016019:Survival Analysis; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase