Extended Histopathology in Immunotoxicity Testing: Interlaboratory Validation Studies.
来源: 浏览量:886 更新日期:2010年1月12日
Toxicol Sci. 2003 Dec 22 [Epub ahead of print].
Germolec DR, Nyska A, Kashon M, Kuper CF, Portier C, Kommineni C, Johnson KA, Luster MI.
Laboratory of Molecular Toxicology/National Toxicology Program, National Institute of Environmental Health Sciences, RTP, NC.
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, 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 with varied expertise in immunohistopathology and in identifying lesions in immune tissues and 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 thymus cortical cellularity, 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 possesses in examining lymphoid tissue and the apparent severity of the specific lesion.