Lisovsky Mikhail, Falkowski Olga, Bhuiya Tawfiqul
Department of Pathology, Long Island Jewish Medical Center, New Hyde Park, NY 11040, USA.
Hum Pathol. 2006 Dec;37(12):1601-6. doi: 10.1016/j.humpath.2006.06.009. Epub 2006 Sep 25.
Although identification of epithelial dysplasia in Barrett's esophagus (BE) is critically important because of a significant risk of progression to invasive adenocarcinoma, the diagnosis of dysplasia may be challenging. Among confounding factors are interobserver variability, tangential sectioning, and severe mucosal inflammation leading to architectural and cytologic atypia similar to that of dysplasia. alpha-methylacyl-coenzyme A racemase (AMACR) is an enzyme involved in beta-oxidation of branched fatty acids and an established marker of prostate cancer. It is expressed in colon adenomas and adenocarcinomas but not in normal colonic epithelium suggesting a role in development of gastrointestinal malignancies. We investigated whether expression of AMACR can be used to identify dysplasia of BE and to distinguish it from reactive atypia. Ninety-six routinely processed biopsy and/or resection specimens (23 negative for dysplasia; 19, low-grade dysplasia; 22, high-grade dysplasia; 16, reactive atypia; and 16, esophageal adenocarcinoma) were immunostained using a monoclonal anti-AMACR antibody p504S. AMACR staining was uniformly negative in the groups negative for dysplasia and with reactive atypia. Only 2 (11%) of 19 specimens with low-grade dysplasia showed positive immunostaning, compared with 14 (64%) of 22 in high-grade dysplasia group. Of 16 specimens, 12 (75%) showed positive staining for AMACR in the adenocarcinoma group. Our data suggest that AMACR immunoreactivity is moderately sensitive in identification of high-grade dysplasia in BE and is highly specific in distinguishing high-grade dysplasia from reactive atypia. Further validation and prospective studies are warranted.
尽管由于巴雷特食管（BE）进展为浸润性腺癌的风险很高，识别其上皮发育异常至关重要，但发育异常的诊断可能具有挑战性。混杂因素包括观察者间的差异、切线切片以及严重的黏膜炎症，这些可导致类似于发育异常的结构和细胞学异型性。α-甲基酰基辅酶A消旋酶（AMACR）是一种参与支链脂肪酸β-氧化的酶，是前列腺癌的既定标志物。它在结肠腺瘤和腺癌中表达，但在正常结肠上皮中不表达，提示其在胃肠道恶性肿瘤发生中起作用。我们研究了AMACR的表达是否可用于识别BE的发育异常并将其与反应性异型性区分开来。使用单克隆抗AMACR抗体p504S对96份常规处理的活检和/或切除标本进行免疫染色（23份发育异常阴性；19份低级别发育异常；22份高级别发育异常；16份反应性异型性；16份食管腺癌）。发育异常阴性组和反应性异型性组中AMACR染色均呈均匀阴性。19份低级别发育异常标本中只有2份（11%）显示免疫染色阳性，而高级别发育异常组22份中有14份（64%）阳性。在16份腺癌标本中，12份（75%）显示AMACR染色阳性。我们的数据表明，AMACR免疫反应性在识别BE的高级别发育异常方面具有中度敏感性，在区分高级别发育异常与反应性异型性方面具有高度特异性。需要进一步的验证和前瞻性研究。
