Extended histopathology in immunotoxicity testing: Interlaboratory validation studies
Extended histopathology in immunotoxicity testing: Interlaboratory validation studies
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DOI：
10.1093/toxsci/kfh049
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发表时间：
2004-03-01
影响因子：
3.8
通讯作者：
Luster, MI
中科院分区：
文献类型：
--
作者：
Germolec, DR;Nyska, A;Luster, MI
人们对使用扩展组织病理学作为免疫毒性评估的主要筛选方法产生了相当大的兴趣。为了确定半定量组织病理学方法在检查淋巴组织的特定结构和结构变化方面的效用，启动了验证工作。本研究使用来自十种测试化学品研究的组织以及来自国家毒理学计划免疫毒理学测试计划的阴性和阳性对照，解决了扩展组织病理学的实验室间重现性。我们检查了经验丰富的毒理学病理学家之间的一致性，他们在免疫组织病理学方面拥有不同的专业知识，可识别免疫组织的病变，以及检测化学效应和剂量反应的个体和组合组织病理学终点的敏感性。因子分析用于估计每个病理学家与所谓的“共同因子”的关联，并使用方差分析方法来评估偏差。病理学家之间的一致性在胸腺中最高，特别是在评估胸腺的皮质细胞结构时；脾滤泡细胞结构以及脾脏和淋巴结生发中心发育良好；脾红髓变最差。此外，识别淋巴组织的组织病理学变化的能力取决于个体病理学家在检查淋巴组织方面所拥有的经验/培训以及特定病变的明显严重程度。
There has been considerable interest in the use of expanded histopathology as a primary screen for immunotoxicity assessment. To determine the utility of a semiquantitative histopathology approach for examining specific structural and architectural changes in lymphoid tissues, a validation effort was initiated. This study addresses the interlaboratory reproducibility of extended histopathology, using tissues from studies of ten test chemicals and both negative and positive controls from the National Toxicology Program's immunotoxicology testing program. We examined the consistency between experienced toxicologic pathologists, who had varied expertise in immunohistopathology in identifying lesions in immune tissues, and in the sensitivity of the individual and combined histopathological endpoints to detect chemical effects and dose response. Factor analysis was used to estimate the association of each pathologist with a so-called "common factor" and analysis-of-variance methods were used to evaluate biases. Agreement between pathologists was highest in the thymus, in particular, when evaluating cortical cellularity of the thymus; good in spleen follicular cellularity and in spleen and lymph node-germinal center development; and poorest in spleen red-pulp changes. In addition, the ability to identify histopathological change in lymphoid tissues was dependent upon the experience/training that the individual pathologist possessed in examining lymphoid tissue and the apparent severity of the specific lesion.