Mammary tumor heterogeneity in wt-ErbB-2 transgenic mice.
Phenotypic and biological heterogeneity was studied in a single transgenic mouse model to determine the level of biological variance. We analyzed 1,258 tumors from 417 MMTV-wt-ErbB-2 transgenic mice, subdivided by casein or soy-based dietary randomization and hormonal treatment. Variance in tumor histologic features, growth pattern, invasion, metastases, and multi-focality were detected in untreated and treated mice. Ninety-three percent (1,174/1,258) of tumors had the solid growth pattern widely reported in this model. However, among the solid tumors, a spectrum of growth patterns, from well-circumscribed tumors with a pseudocapsule to locally invasive or highly aggressive, metastatic subtype, was observed. Of the non-solid tumors, glandular features were prominent in 84 (7%). Adenocarcinomas included papillary, acinar/glandular, and adenosquamous subtypes. Adenosquamous tumors were exclusively observed in the group of mice treated on a short-term basis with estrogen. In contrast to the reported literature for this transgenic mouse model, mammary tumors were multifocal in the majority of cases (303 of 417 mice, or 73%). Results of this extensive study of a single transgenic model of mammary tumorigenesis indicate phenotypic and biological heterogeneity not previously associated with this transgenic mouse. These data support a complex, multistep process of carcinogenesis and clonal evolution, with biological and phenotypic variance similar to that observed in human mammary cancer development.
Kosanke
Stanley
S
Department of Pathology and College of Medicine, Oklahoma University Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
Edgerton
Susan M
SM
Moore
Dan
D
Yang
XiaoHe
X
Mason
Terza
T
Alvarez
Kathy
K
Jones
Lynn
L
Kim
Aeree
A
Thor
Ann D
AD
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000818:Animals; D004032:Diet; D005260:Female; D018734:Genes, erbB-2; D015674:Mammary Neoplasms, Animal / Q000235:genetics* / Q000473:pathology; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic