前列腺癌中雌激素受体β2免疫组化的病理学家评分与数字图像分析的定量比较及可重复性
Quantitative comparison and reproducibility of pathologist scoring and digital image analysis of estrogen receptor β2 immunohistochemistry in prostate cancer.
作者信息
Rizzardi Anthony E, Zhang Xiaotun, Vogel Rachel Isaksson, Kolb Suzanne, Geybels Milan S, Leung Yuet-Kin, Henriksen Jonathan C, Ho Shuk-Mei, Kwak Julianna, Stanford Janet L, Schmechel Stephen C
机构信息
Department of Pathology, University of Washington, 908 Jefferson Street, Room 2NJB244, Seattle, WA, 98104, USA.
Department of Pathology, University of Washington, 300 Ninth Ave, Research & Training Building, Room 421, Seattle, WA, 98104, USA.
出版信息
Diagn Pathol. 2016 Jul 11;11(1):63. doi: 10.1186/s13000-016-0511-5.
BACKGROUND
Digital image analysis offers advantages over traditional pathologist visual scoring of immunohistochemistry, although few studies examining the correlation and reproducibility of these methods have been performed in prostate cancer. We evaluated the correlation between digital image analysis (continuous variable data) and pathologist visual scoring (quasi-continuous variable data), reproducibility of each method, and association of digital image analysis methods with outcomes using prostate cancer tissue microarrays (TMAs) stained for estrogen receptor-β2 (ERβ2).
METHODS
Prostate cancer TMAs were digitized and evaluated by pathologist visual scoring versus digital image analysis for ERβ2 staining within tumor epithelium. Two independent analysis runs were performed to evaluate reproducibility. Image analysis data were evaluated for associations with recurrence-free survival and disease specific survival following radical prostatectomy.
RESULTS
We observed weak/moderate Spearman correlation between digital image analysis and pathologist visual scores of tumor nuclei (Analysis Run A: 0.42, Analysis Run B: 0.41), and moderate/strong correlation between digital image analysis and pathologist visual scores of tumor cytoplasm (Analysis Run A: 0.70, Analysis Run B: 0.69). For the reproducibility analysis, there was high Spearman correlation between pathologist visual scores generated for individual TMA spots across Analysis Runs A and B (Nuclei: 0.84, Cytoplasm: 0.83), and very high correlation between digital image analysis for individual TMA spots across Analysis Runs A and B (Nuclei: 0.99, Cytoplasm: 0.99). Further, ERβ2 staining was significantly associated with increased risk of prostate cancer-specific mortality (PCSM) when quantified by cytoplasmic digital image analysis (HR 2.16, 95 % CI 1.02-4.57, p = 0.045), nuclear image analysis (HR 2.67, 95 % CI 1.20-5.96, p = 0.016), and total malignant epithelial area analysis (HR 5.10, 95 % CI 1.70-15.34, p = 0.004). After adjusting for clinicopathologic factors, only total malignant epithelial area ERβ2 staining was significantly associated with PCSM (HR 4.08, 95 % CI 1.37-12.15, p = 0.012).
CONCLUSIONS
Digital methods of immunohistochemical quantification are more reproducible than pathologist visual scoring in prostate cancer, suggesting that digital methods are preferable and especially warranted for studies involving large sample sizes.
背景
数字图像分析相较于传统病理学家对免疫组织化学的视觉评分具有优势，尽管在前列腺癌中很少有研究探讨这些方法的相关性和可重复性。我们使用雌激素受体-β2（ERβ2）染色的前列腺癌组织微阵列（TMA）评估了数字图像分析（连续变量数据）与病理学家视觉评分（准连续变量数据）之间的相关性、每种方法的可重复性，以及数字图像分析方法与预后的关联。
方法
对前列腺癌TMA进行数字化处理，并由病理学家通过视觉评分与数字图像分析评估肿瘤上皮内的ERβ2染色情况。进行了两次独立的分析运行以评估可重复性。对图像分析数据进行评估，以探讨其与前列腺癌根治术后无复发生存率和疾病特异性生存率的关联。
结果
我们观察到数字图像分析与肿瘤细胞核的病理学家视觉评分之间存在弱/中度Spearman相关性（分析运行A：0.42，分析运行B：0.41），数字图像分析与肿瘤细胞质的病理学家视觉评分之间存在中度/强相关性（分析运行A：0.70，分析运行B：0.69）。对于可重复性分析，在分析运行A和B中针对单个TMA斑点生成的病理学家视觉评分之间存在高度Spearman相关性（细胞核：0.84，细胞质：0.83），在分析运行A和B中针对单个TMA斑点的数字图像分析之间存在非常高的相关性（细胞核：0.99，细胞质：0.99）。此外，当通过细胞质数字图像分析（HR 2.16，95%CI 1.02 - 4.57，p = 0.045）、细胞核图像分析（HR 2.67，95%CI 1.20 - 5.96，p = 0.016）和总恶性上皮面积分析（HR 5.10，95%CI 1.70 - 15.34，p = 0.004）对ERβ2染色进行量化时，ERβ2染色与前列腺癌特异性死亡率（PCSM）风险增加显著相关。在调整临床病理因素后，只有总恶性上皮面积的ERβ2染色与PCSM显著相关（HR 4.08，95%CI 1.37 - 12.15，p = 0.012）。
结论
在前列腺癌中，免疫组织化学定量的数字方法比病理学家视觉评分更具可重复性，这表明数字方法更可取，尤其适用于涉及大样本量的研究。
Zotero 插件