Prostatic Intraepithelial neoplasia in genetically engineered mice
Prostatic Intraepithelial neoplasia in genetically engineered mice
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DOI：
10.1016/s0002-9440(10)64228-9
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发表时间：
2002-08-01
影响因子：
6
通讯作者：
Cardiff, RD
中科院分区：
文献类型：
--
作者：
Park, JH;Walls, JE;Cardiff, RD
研究了几种人类前列腺癌小鼠模型，以识别和表征含有非典型上皮细胞灶的潜在前驱病变。这些病变表现出一系列的变化，表明其向恶性发展。基于这些观察，我们提出了一个分级系统来对基因工程小鼠（GEM）的前列腺上皮内瘤变（PIN）进行分类。根据其结构、分化模式和细胞学非典型性程度，将GEM PIN分为4个等级。PIN I型病变有一层或两层非典型细胞。PIN H有两层或两层以上的非典型细胞。PIN III型有大的多形性细胞核，核仁突出，细胞往往累及整个管腔，管廓扩大。PIN IV病变包含非典型细胞，这些细胞充满管腔并局部膨出并经常损害纤维肌鞘。在同一队列中，低年级pin首先出现的时间比高年级pin出现的时间早。形态计量学和免疫组织化学分析证实了进行性改变。虽然PIN IV在小鼠中的恶性潜能尚未得到证实，但GEM PIN与人类PIN相似。PIN分类系统是对GEM中这些病变的生物学潜力进行系统评估的第一步。
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 H 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.