Expression of α-methylacyl coenzyme A racemase in the dysplasia carcinoma sequence associated with Barrett’s esophagus

Abstract

Two different studies demonstrated a-methylacyl coenzyme A racemase (AMACR) to be a highly specific marker in Barrett's neoplastic lesions. Reactive atypia was positive in 3/30 cases in these studies. We present a retrospective study of early Barrett's adenocarcinoma treated with surgery (2000-2005, n ¼ 29; M:F ¼ 5:1, median age 67 years). We analyzed the role of AMACR expression in reactive and neoplastic lesions associated with the disease of 77 different specimens (60 biopsy and 17 surgical specimens) of these patients. In our cohort, 70% of cases demonstrated infiltration of the submucosa, 38% were poorly differentiated, and/or 31% demonstrated lymph vessel infiltration. We used a multi-tissue array, with reactive and neoplastic samples for each patient to analyze the immunoreactivity of AMACR. Barrett's epithelium that was negative for dysplasia and columnar epithelial cell changes indefinite for dysplasia (n ¼ 30) did not demonstrate AMACR immunoreactivity. AMACR immunoreactivity was demonstrated in 27% (8/30) of cases of Barrett's epithelium with columnar epithelial cell changes indefinite for dysplasia. Altogether 91% of cases with low-grade dysplasia were AMACR-positive and 96% of cases with high-grade dysplasia and early Barrett's adenocarcinoma were positive for AMACR. In summary, the sensitivity of AMACR expression in low-grade dysplasia and subsequent early Barrett's adenocarcinoma was significantly higher in our study compared with previous data. This might be a new diagnostic marker for dysplasia carcinoma sequence in Barrett's low-grade neoplastic lesions. Further studies are required to investigate this point with well-defined controls having at least 5-years follow-up.

Anti-phosphorylated histone H3 expression in Barrett's esophagus, low-grade dysplasia, high-grade dysplasia, and adenocarcinoma

“…That study also found AMACR staining in 21% of samples that were originally diagnosed as indefinite for dysplasia. These findings were supported by the results of a study from Scheil-Bertram et al 19 However, a recent study by Shi et al 20 showed AMACR expression at the rates of 12% in Barrett's esophagus without dysplasia, 47% in indefinite for dysplasia, 44% in low-grade dysplasia, 93% in highgrade dysplasia, and 96% in adenocarcinoma, suggesting that AMACR has lower specificity for distinguishing between Barrett's esophagus with and without dysplasia. The strength of AMACR is that the test is a simple qualitative assessment of positive cells.…”

IMP3 Immunoreactivity is More Sensitive Than AMACR in Detecting Dysplastic Epithelium and Early Adenocarcinoma in Barrett Esophagus

“…2 However, in some case, the identification of dysplasia can be quite challenging. Recently, several studies have explored the expression of AMACR in BE's neoplastic lesions, [5][6][7] and although in 1 study 7 AMACR was expressed in 90% of the BE-LGD, in the other 2 studies, lower percentages of AMACRpositive cases were identified: 37.5% and 10.5%, respectively. 5,6 Furthermore, collectively, these previous FIGURE 2.…”

“…5 In the series of Xu et al, 12 8/17 (47.1%) cases of BE-IND were AMACR positive, but again, only weakly (1+). In the larger group of BE-IND studied so far by immunostaining for AMACR, 7 8/ 30 (26.7%) showed AMACR positivity, but all with a weak staining pattern. In our study, as in that of Lisovsky et al, 6 none of the 10 and 16 cases, respectively, was positive for AMACR.…”

“…AMACR indicates a-methylacyl coenzyme A racemase; IMP3, insulin-like growth factor-II mRNA-binding protein 3; LGD, low-grade dysplasia. studies [5][6][7] have demonstrated the expression of AMACR to be between 63.6% and 95.7% for BE-HGD and between 75% and 96.3% for BE-invasive adenocarcinoma. In the current study, we found that only 16.7% of the cases of BE-LGD, 25% of BE-HGD, and 62.5% of EAC expressed AMACR.…”

“…3 Biomarkers that have been advocated as helpful in differentiating true dysplasia from reactive changes include p16 (INK-4A/CDXN2A), cyclin D1 (CCND1), p53, Ki-67, and, more recently, a-methylacyl coenzyme A racemase (AMACR). [4][5][6][7] AMACR is an enzyme that catalyzes the racemization of a-methyl branched carboxylic coenzyme A thioesters. It has been reported to be expressed in 79% to 100% of prostate adenocarcinomas and in 80% of high-grade prostatic intraepithelial neoplasias, but it is rarely expressed in the normal, non-neoplastic prostate tissue.…”