Cyclin A Immunocytology as a Risk Stratification Tool for Barrett's Esophagus Surveillance

• Published in: Clinical cancer research 2007-01, Vol.13 (2), p.659-665
• Main Authors: LAO-SIRIEIX, Pierre, LOVAT, Laurence, FITZGERALD, Rebecca C
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - diagnosis; Adenocarcinoma - metabolism; Aged; Antineoplastic agents; Barrett Esophagus - diagnosis; Barrett Esophagus - metabolism; Biological and medical sciences; biomarker; Biomarkers, Tumor; Biopsy; Case-Control Studies; Cell Proliferation; Cohort Studies; Cyclin A - biosynthesis; cytology; Disease Progression; esophageal adenocarcinoma; Esophageal Neoplasms - diagnosis; Esophageal Neoplasms - metabolism; Esophagus; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Regulation, Neoplastic; Humans; Mass Screening - methods; Medical sciences; Middle Aged; Other diseases. Semiology; Pharmacology. Drug treatments; proliferation; Risk; Sensitivity and Specificity
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-06-1385

Purpose: 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. Experimental Design: 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. Results: 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%. Conclusions: 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.