Park Jae-Hak, Walls Judy E, Galvez Jose J, Kim Minjung, Abate-Shen Cory, Shen Michael M, Cardiff Robert D
Center for Comparative Medicine and Department of Medical Pathology, University of California, Davis, California 95616, USA.
Am J Pathol. 2002 Aug;161(2):727-35. doi: 10.1016/S0002-9440(10)64228-9.
Several mouse models of human prostate cancer were studied to identify and characterize potential precursor lesions containing foci of atypical epithelial cells. These lesions exhibit a sequence of changes suggesting progressive evolution toward malignancy. Based on these observations, a grading system is proposed to classify prostatic intraepithelial neoplasia (PIN) in genetically engineered mice (GEM). Four grades of GEM PIN are proposed based on their architecture, differentiation pattern, and degree of cytological atypia. PIN I lesions have one or two layers of atypical cells. PIN II has two or more layers of atypical cells. PIN III has large, pleomorphic nuclei with prominent nucleoli and the cells tend to involve the entire lumen with expansion of the duct outlines. PIN IV lesions contain atypical cells that fill the lumen and bulge focally into, and frequently compromise, the fibromuscular sheath. Within the same cohorts, the lower grade PINs first appear earlier than the higher grades. Morphometric and immunohistochemical analyses confirm progressive change. Although the malignant potential of PIN IV in mice has not been proven, GEM PIN is similar to human PIN. This PIN classification system is a first step toward a systematic evaluation of the biological potential of these lesions in GEM.
对几种人类前列腺癌小鼠模型进行了研究，以识别和表征含有非典型上皮细胞灶的潜在前驱病变。这些病变呈现出一系列变化，提示其向恶性肿瘤的逐步演变。基于这些观察结果，提出了一种分级系统，用于对基因工程小鼠（GEM）中的前列腺上皮内瘤变（PIN）进行分类。根据其结构、分化模式和细胞异型程度，提出了四级GEM PIN。PIN I病变有一层或两层非典型细胞。PIN II有两层或更多层非典型细胞。PIN III有大的、多形性核且核仁突出，细胞倾向于累及整个管腔，导管轮廓扩张。PIN IV病变包含填充管腔并局部突入纤维肌鞘且常破坏纤维肌鞘的非典型细胞。在同一组中，较低级别的PIN首先出现的时间早于较高级别的PIN。形态计量学和免疫组化分析证实了其渐进性变化。虽然小鼠中PIN IV的恶性潜能尚未得到证实，但GEM PIN与人类PIN相似。这种PIN分类系统是朝着系统评估GEM中这些病变的生物学潜能迈出的第一步。
