Histological differences between ErbB/Ras and wnt pathway transgenic mammary tumors

被引:147
作者
Rosner, A
Miyoshi, K
Landesman-Bollag, E
Xu, X
Seldin, DC
Moser, AR
MacLeod, CL
Shyamala, G
Gillgrass, AE
Cardiff, RD
机构
[1] Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA
[2] NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA
[3] Univ Tokushima, Sch Dent, Dept Biochem, Tokushima 770, Japan
[4] Boston Univ, Sch Med, Boston, MA 02118 USA
[5] Univ Wisconsin, Dept Human Oncol, Madison, WI USA
[6] Univ Calif San Diego, Sch Med, Ctr Canc, Dept Med, La Jolla, CA 92093 USA
[7] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA
[8] McMaster Univ, Dept Med Sci, Hamilton, ON, Canada
关键词
D O I
10.1016/S0002-9440(10)64269-1
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
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.
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收藏
页码:1087 / 1097
页数:11
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