Histological differences between ErbB/Ras and wnt pathway transgenic mammary tumors
Histological differences between ErbB/Ras and wnt pathway transgenic mammary tumors
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DOI：
10.1016/s0002-9440(10)64269-1
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发表时间：
2002-09-01
影响因子：
6
通讯作者：
Cardiff, RD
中科院分区：
文献类型：
--
作者：
Rosner, A;Miyoshi, K;Cardiff, RD
为了研究表型-基因型相关性，ErbB/Ras通路肿瘤将来自四个不同机构的肿瘤（ErbB 2、c-Neu、c-Neu突变体、多瘤病毒中T抗原基因（PyV-mT）、Ras的转基因，以及ErbB 2/Neu与ErbB 3和孕酮受体的双转基因）与Wnt途径肿瘤[转基因Wnt 1、Wnt 10 b，显性阴性糖原合成酶激酶3-β，β-连环蛋白，和结肠腺瘤性息肉病基因（Apc）的自发突变体]。ErbB/Ras途径肿瘤倾向于形成由具有丰富细胞质的低分化细胞组成的实性结节。ErbB/Ras途径肿瘤也具有稀少的基质并且缺乏肌上皮或鳞状分化。相比之下，Wnt途径肿瘤表现出肌上皮、腺泡或腺分化，并且经常表现出这些分化的组合。鳞状上皮化生是常见的，可能包括转分化为表皮和皮拉尔结构。大多数Wnt通路肿瘤形成细长、分支小管的漫画，并具有发育良好的基质、炎性浸润和推缘。相互作用基因如蛋白激酶CK 2 α（酪蛋白激酶II）和成纤维细胞生长因子（Fgf）Int 2/Fgf 3或角质形成细胞生长因子（Kgf/Fgf 7）的转基因肿瘤也具有Wnt途径表型。由于ErbB/Ras和Wnt通路的肿瘤是如此不同，可以很容易地确定使用常规苏木精和伊红切片，我们建议，通路病理学是适用于基础和临床癌症研究。
To study phenotype-genotype correlations, ErbB/Ras pathway tumors (transgenic for ErbB2, c-Neu, mutants of c-Neu, polyomavirus middle T antigene (PyV-mT), Ras, and bi-transgenic for ErbB2/Neu with ErbB3 and with progesterone receptor) from four different institutions were histopathologically compared with Wnt pathway tumors [transgenes Wnt1, Wnt10b, dominant-negative glycogen synthase kinase 3-beta, beta-Catenin, and spontaneous mutants of adenomatous polyposis coli gene (Apc)]. ErbB/Ras pathway tumors tend to form solid nodules consisting of poorly differentiated cells with abundant cytoplasm. ErbB/Ras pathway tumors also have scanty stroma and lack myoepithelial or squamous differentiation. In contrast, Wnt pathway tumors exhibit myoepithelial, acinar, or glandular differentiation, and, frequently, combinations of these. Squamous metaplasia is frequent and may include transdifferentiation to epidermal and pilar structures. Most Wnt pathway tumors form caricatures of elongated, branched ductules, and have well-developed stroma, inflammatory infiltrates, and pushing margins. Tumors transgenic for interacting genes such as protein kinase CK2alpha (casein kinase II), and the fibroblast growth factors (Fgf) Int2/Fgf3 or keratinocyte growth factor (Kgf/Fgf7) also have the Wnt pathway phenotype. Because the tumors from the ErbB/Ras and the Wnt pathway are so distinct and can be readily identified using routine hematoxylin and eosin sections, we suggest that pathway pathology is applicable in both basic and clinical cancer research.