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.
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.
Authors: Urs von Holzen; Tina Chen; Amelie Boquoi; Joel E Richter; Gary W Falk; Andres J Klein-Szanto; Harry Cooper; Sam Litwin; David S Weinberg; Greg H Enders Journal: Transl Oncol Date: 2010-02 Impact factor: 4.243
Authors: Amel Saadi; Nicholas B Shannon; Pierre Lao-Sirieix; Maria O'Donovan; Elaine Walker; Nicholas J Clemons; James S Hardwick; Chunsheng Zhang; Madhumita Das; Vicki Save; Marco Novelli; Frances Balkwill; Rebecca C Fitzgerald Journal: Proc Natl Acad Sci U S A Date: 2010-01-13 Impact factor: 11.205
Authors: Dennis L Chao; Carissa A Sanchez; Patricia C Galipeau; Patricia L Blount; Thomas G Paulson; David S Cowan; Kamran Ayub; Robert D Odze; Peter S Rabinovitch; Brian J Reid Journal: Clin Cancer Res Date: 2008-11-01 Impact factor: 12.531
Authors: J Nwachokor; O Tawfik; M Danley; S Mathur; J House; P Sharma; L K Christenson; A Bansal Journal: Dis Esophagus Date: 2017-09-01 Impact factor: 3.429