Nwachokor J, Tawfik O, Danley M, Mathur S, House J, Sharma P, Christenson L K, Bansal A
Departments of Internal Medicine.
Pathology and Laboratory Medicine, the University of Kansas School of Medicine.
Dis Esophagus. 2017 Sep 1;30(9):1-8. doi: 10.1093/dote/dox023.
Chemoprevention and risk-stratification studies in Barrett's esophagus (BE) rely on biomarkers but the variability in their temporal and spatial expression is unknown. If such variability exists, it will impact sampling techniques and sample size calculations. Specimens from three levels of biopsies over two serial endoscopies in nondysplastic BE patients were analyzed for aneuploidy, proliferation markers (Ki67, Mcm2), and cell cycle markers (cyclin A and cyclin D1). A modification of the image cytometry technique, where cytokeratin staining automatically distinguished epithelial and stromal cells, measured aneuploidy on whole tissue sections. Other biomarkers were studied by immunohistochemistry. Coefficient of variability (SD/mean) was calculated; a value <10% indicated low variability. A total of 120 specimens (20 subjects each with three biopsy levels at two time points) from nondysplastic BE patients (71 ± 8.8 years, all Caucasian, 90% males, C5.1M7.5 ± 3.4 cm) were analyzed. The mean interval between endoscopies was 32.8 ± 8.4 months. Aneuploidy had a spatial variability of 6.8% at visit 1 (mean diploid index: 1.1 ± 0.09) and 7.9% at visit 2 (mean diploid index: 1.1 ± 0.06) and a temporal variability of 7.0-8.1% for the three levels. For other biomarkers, the spatial variability ranged from ∼5 to 30% at visit 1 and 11-92% at visit 2 and the temporal variability ranged from 0 to 77%. To conclude, of all the biomarkers, only aneuploidy had both spatial and temporal variability of <10%. Spatial and temporal variability were biomarker dependent and could be as high as 90% even without progression. These data will be useful to design chemoprevention and risk-stratification studies in BE.
巴雷特食管（BE）的化学预防和风险分层研究依赖生物标志物，但其时空表达的变异性尚不清楚。如果存在这种变异性，将会影响采样技术和样本量计算。对非发育异常的BE患者在两次连续内镜检查中三个活检水平的标本进行非整倍体、增殖标志物（Ki67、Mcm2）和细胞周期标志物（细胞周期蛋白A和细胞周期蛋白D1）分析。采用一种图像细胞术技术的改良方法，通过细胞角蛋白染色自动区分上皮细胞和基质细胞，在整个组织切片上测量非整倍体。通过免疫组织化学研究其他生物标志物。计算变异系数（标准差/均值）；值<10%表明变异性低。共分析了120份来自非发育异常BE患者（71±8.8岁，均为白种人，90%为男性，C5.1M7.5±3.4 cm）的标本（20名受试者，每个受试者在两个时间点有三个活检水平）。内镜检查之间的平均间隔为32.8±8.4个月。非整倍体在第1次就诊时的空间变异性为6.8%（平均二倍体指数：1.1±0.09），在第2次就诊时为7.9%（平均二倍体指数：1.1±0.06），三个水平的时间变异性为7.0 - 8.1%。对于其他生物标志物，第1次就诊时空间变异性范围约为5%至30%，第2次就诊时为11%至92%，时间变异性范围为0至77%。总之，在所有生物标志物中，只有非整倍体的时空变异性<10%。时空变异性取决于生物标志物，即使没有进展也可能高达90%。这些数据将有助于设计BE的化学预防和风险分层研究。
