Departments of Pathology, University of Minnesota, Minneapolis.
Departments of Gastroenterology, University of Minnesota, Minneapolis.
Am J Clin Pathol. 2020 Apr 15;153(5):695-704. doi: 10.1093/ajcp/aqaa004.
Many studies have shown poor reproducibility among pathologists for diagnosing dysplasia in Barrett's esophagus (BE). Immunohistochemical stains (IHC) are not widely used due to overlapping expression patterns in reactive and dysplastic processes. We hypothesized that markers involved in cell-cycle (cyclin D1, Ki-67, P16), differentiation/cell-cell interaction (β-catenin, SATB2 CD44, OCT4) and senescence (γH2AX) would produce different results in reactive and dysplastic processes.
A micrograph album of 40 H&E and matching IHCs depicting optimally oriented lesions were evaluated independently by 3 pathologists. Expression was scored separately in the surface, isthmus, and base regions of the glands.
Statistical analysis showed that surface Ki-67 expression showed the largest difference in expression and smallest P value (P < .001) for identifying dysplasia. At a cutoff level of 5% or less, negative predictive value (NPV) was 100%. κ correlation between pathologists improved from substantial to almost perfect (0.70-0.95) using ancillary surface Ki-67.
A case-control study with glass slides including all diagnostic categories using this parameter confirmed improved κ correlation among pathologists (0.29 vs 0.60), better correlation with outcomes (76% vs 69%), increased odd risks (15.3) for progression in positive cases, and an improvement in sensitivity (88% vs 64%) and NPV (88% vs 73%) compared to histology alone.
许多研究表明,病理学家在诊断 Barrett 食管(BE)异型增生方面的重复性较差。由于在反应性和异型增生过程中存在重叠的表达模式,免疫组织化学染色(IHC)并未广泛应用。我们假设,参与细胞周期(cyclin D1、Ki-67、P16)、分化/细胞-细胞相互作用(β-catenin、SATB2、CD44、OCT4)和衰老(γH2AX)的标志物在反应性和异型增生过程中会产生不同的结果。
通过 3 位病理学家独立评估了 40 张 H&E 和匹配的 IHC 微图专辑,这些微图专辑描绘了最佳定向病变。在腺体的表面、峡部和基底区域分别对表达进行评分。
统计分析表明,表面 Ki-67 表达在识别异型增生方面表现出最大的差异和最小的 P 值(P <.001)。在截断值为 5%或以下时,阴性预测值(NPV)为 100%。使用辅助表面 Ki-67,病理学家之间的κ相关性从实质性提高到几乎完美(0.70-0.95)。
使用该参数的玻璃载玻片包括所有诊断类别进行病例对照研究,证实了病理学家之间的κ相关性得到了改善(0.29 对 0.60),与结果的相关性更好(76%对 69%),阳性病例进展的优势比(odds ratio,OR)增加(15.3),敏感性(88%对 64%)和 NPV(88%对 73%)提高,与单独的组织学相比。