Lao-Sirieix Pierre, Lovat Laurence, Fitzgerald Rebecca C
Medical Research Council-Cancer Cell Unit, Medical Research Council/Hutchison Research Centre, Hills Road, Cambridge, UK.
Clin Cancer Res. 2007 Jan 15;13(2 Pt 1):659-65. doi: 10.1158/1078-0432.CCR-06-1385.
Endoscopic surveillance of Barrett's esophagus (BE) by histopathologic biopsy assessment is suboptimal. A proliferation marker, minichromosome maintenance protein 2, has potential as a biomarker but lacks specificity. We hypothesized that cyclin A, which detects a proportion of proliferating cells, would be more specific. Because cytologic sampling has clinical advantages, we also evaluated the efficacy of cyclin A in endoscopic brushing samples.
A cross-sectional cyclin A immunostaining study was done in 77 patients attending for BE surveillance and 17 patients undergoing evaluation of esophageal adenocarcinoma. The control tissues were as follows: 30 squamous esophagus, 20 gastric antrum, and 13 duodenum. A nested case-control study was done within the same surveillance cohort (16 progressors compared with 32 matched controls) to determine the relative risk for progression. Immunocytology was done for endoscopic brushings collected prospectively from 75 BE +/- dysplasia and 33 esophageal adenocarcinomas.
Surface expression of cyclin A in BE samples correlated with the degree of dysplasia (P = 0.016). In the case-control cohort, patients with biopsies expressing cyclin A at the surface were more likely to progress to adenocarcinoma than those who did not (odds ratio, 7.5; 95% confidence interval, 1.8-30.7). The sensitivity and specificity of cyclin A expression in brushings for the detection of high-grade dysplasia and cancer patients were 97.8% and 58.7%, respectively. The associated negative predictive value was 97.4%.
Cyclin A immunopositivity correlates with cancer risk. Application of this marker to endoscopic brushings could be used as a first step to identify BE patients with the highest risk of progression.
通过组织病理学活检评估对巴雷特食管（BE）进行内镜监测并不理想。一种增殖标志物，微小染色体维持蛋白2，有作为生物标志物的潜力，但缺乏特异性。我们推测细胞周期蛋白A，它能检测一部分增殖细胞，会更具特异性。由于细胞学采样具有临床优势，我们还评估了细胞周期蛋白A在内镜刷检样本中的效能。
对77名接受BE监测的患者和17名接受食管腺癌评估的患者进行了一项横断面细胞周期蛋白A免疫染色研究。对照组织如下：30例鳞状食管、20例胃窦和13例十二指肠。在同一监测队列中进行了一项巢式病例对照研究（16例进展者与32例匹配对照）以确定进展的相对风险。对前瞻性收集的75例BE伴或不伴发育异常及33例食管腺癌的内镜刷检样本进行免疫细胞分析。
BE样本中细胞周期蛋白A的表面表达与发育异常程度相关（P = 0.016）。在病例对照队列中，活检显示表面表达细胞周期蛋白A的患者比未表达的患者更有可能进展为腺癌（优势比，7.5；95%置信区间，1.8 - 30.7）。刷检样本中细胞周期蛋白A表达对高级别发育异常和癌症患者检测的敏感性和特异性分别为97.8%和58.7%。相关的阴性预测值为97.4%。
细胞周期蛋白A免疫阳性与癌症风险相关。将该标志物应用于内镜刷检可作为识别进展风险最高的BE患者的第一步。
