title: Pathway pathology: histological differences between ErbB/Ras and Wnt pathway transgenic mammary tumors.
abstract: 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 IIalpha), 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.
authors.affiliation: Center for Comparative Medicine, University of California, Davis 95616, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Rosner
authors.forename: Keiko
authors.initials: K
authors.lastname: Miyoshi
authors.forename: Esther
authors.initials: E
authors.lastname: Landesman-Bollag
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.forename: David C
authors.initials: DC
authors.lastname: Seldin
authors.forename: Amy R
authors.initials: AR
authors.lastname: Moser
authors.forename: Carol L
authors.initials: CL
authors.lastname: MacLeod
authors.forename: G
authors.initials: G
authors.lastname: Shyamala
authors.forename: Amy E
authors.initials: AE
authors.lastname: Gillgrass
authors.forename: Robert D
authors.initials: RD
authors.lastname: Cardiff
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018815:Genes, erbB; D011905:Genes, ras; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D019076:Transgenes; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins
chemical_list: D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D029961:Zebrafish Proteins