Prichard Jeffrey W, Davison Jon M, Campbell Bruce B, Repa Kathleen A, Reese Lia M, Nguyen Xuan M, Li Jinhong, Foxwell Tyler, Taylor D Lansing, Critchley-Thorne Rebecca J
Department of Pathology and Laboratory Medicine, Geisinger Medical Center, Danville, PA 17822, USA.
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
J Pathol Inform. 2015 Aug 31;6:48. doi: 10.4103/2153-3539.163987. eCollection 2015.
Current histologic methods for diagnosis are limited by intra- and inter-observer variability. Immunohistochemistry (IHC) methods are frequently used to assess biomarkers to aid diagnoses, however, IHC staining is variable and nonlinear and the manual interpretation is subjective. Furthermore, the biomarkers assessed clinically are typically biomarkers of epithelial cell processes. Tumors and premalignant tissues are not composed only of epithelial cells but are interacting systems of multiple cell types, including various stromal cell types that are involved in cancer development. The complex network of the tissue system highlights the need for a systems biology approach to anatomic pathology, in which quantification of system processes is combined with informatics tools to produce actionable scores to aid clinical decision-making.
Here, we describe a quantitative, multiplexed biomarker imaging approach termed TissueCypher™ that applies systems biology to anatomic pathology. Applications of TissueCypher™ in understanding the tissue system of Barrett's esophagus (BE) and the potential use as an adjunctive tool in the diagnosis of BE are described.
The TissueCypher™ Image Analysis Platform was used to assess 14 epithelial and stromal biomarkers with known diagnostic significance in BE in a set of BE biopsies with nondysplastic BE with reactive atypia (RA, n = 22) and Barrett's with high-grade dysplasia (HGD, n = 17). Biomarker and morphology features were extracted and evaluated in the confirmed BE HGD cases versus the nondysplastic BE cases with RA.
Multiple image analysis features derived from epithelial and stromal biomarkers, including immune biomarkers and morphology, showed significant differences between HGD and RA.
The assessment of epithelial cell abnormalities combined with an assessment of cellular changes in the lamina propria may serve as an adjunct to conventional pathology in the assessment of BE.
当前用于诊断的组织学方法受观察者内和观察者间差异的限制。免疫组织化学（IHC）方法经常用于评估生物标志物以辅助诊断，然而，IHC染色具有变异性和非线性，且人工判读具有主观性。此外，临床上评估的生物标志物通常是上皮细胞过程的生物标志物。肿瘤和癌前组织不仅由上皮细胞组成，而是多种细胞类型相互作用的系统，包括参与癌症发展的各种基质细胞类型。组织系统的复杂网络凸显了对解剖病理学采用系统生物学方法的必要性，其中系统过程的量化与信息学工具相结合，以产生可用于临床决策的可操作评分。
在此，我们描述了一种称为TissueCypher™的定量、多重生物标志物成像方法，该方法将系统生物学应用于解剖病理学。描述了TissueCypher™在理解巴雷特食管（BE）组织系统中的应用以及作为BE诊断辅助工具的潜在用途。
使用TissueCypher™图像分析平台，在一组具有反应性异型增生的非发育异常BE（RA，n = 22）和高级别发育异常的巴雷特食管（HGD，n = 17）的BE活检中，评估14种在BE中具有已知诊断意义的上皮和基质生物标志物。在确诊的BE HGD病例与具有RA的非发育异常BE病例中提取并评估生物标志物和形态特征。
源自上皮和基质生物标志物（包括免疫生物标志物和形态）的多个图像分析特征显示HGD和RA之间存在显著差异。
上皮细胞异常评估与固有层细胞变化评估相结合，可作为BE评估中传统病理学的辅助手段。
