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Breast Cancer Research
Published in: Breast Cancer Research 6/2004

Open Access 01-12-2004 | Research article

Proteotypic classification of spontaneous and transgenic mammary neoplasms

Authors: Igor Mikaelian, Natalie Blades, Gary A Churchill, Karen Fancher, Barbara B Knowles, Janan T Eppig, John P Sundberg

Published in: Breast Cancer Research | Issue 6/2004

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Abstract

Introduction

Mammary tumors in mice are categorized by using morphologic and architectural criteria. Immunolabeling for terminal differentiation markers was compared among a variety of mouse mammary neoplasms because expression of terminal differentiation markers, and especially of keratins, provides important information on the origin of neoplastic cells and their degree of differentiation.

Methods

Expression patterns for terminal differentiation markers were used to characterize tumor types and to study tumor progression in transgenic mouse models of mammary neoplasia (mice overexpressing Neu (Erbb2), Hras, Myc, Notch4, SV40-TAg, Tgfa, and Wnt1), in spontaneous mammary carcinomas, and in mammary neoplasms associated with infection by the mouse mammary tumor virus (MMTV).

Results

On the basis of the expression of terminal differentiation markers, three types of neoplasm were identified: first, simple carcinomas composed exclusively of cells with a luminal phenotype are characteristic of neoplasms arising in mice transgenic for Neu, Hras, Myc, Notch4, and SV40-TAg; second, 'complex carcinomas' displaying luminal and myoepithelial differentiation are characteristic of type P tumors arising in mice transgenic for Wnt1, neoplasms arising in mice infected by the MMTV, and spontaneous adenosquamous carcinomas; and third, 'carcinomas with epithelial to mesenchymal transition (EMT)' are a characteristic feature of tumor progression in Hras-, Myc-, and SV40-TAg-induced mammary neoplasms and PL/J and SJL/J mouse strains, and display de novo expression of myoepithelial and mesenchymal cell markers. In sharp contrast, EMT was not detected in papillary adenocarcinomas arising in BALB/cJ mice, spontaneous adenoacanthomas, neoplasms associated with MMTV-infection, or in neoplasms arising in mice transgenic for Neu and Wnt1.

Conclusions

Immunohistochemical profiles of complex neoplasms are consistent with a stem cell origin, whereas simple carcinomas might originate from a cell committed to the luminal lineage. In addition, these results suggest that the initiating oncogenic events determine the morphologic features associated with cancer progression because EMT is observed only in certain types of neoplasm.
Appendix
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Metadata
Title
Proteotypic classification of spontaneous and transgenic mammary neoplasms
Authors
Igor Mikaelian
Natalie Blades
Gary A Churchill
Karen Fancher
Barbara B Knowles
Janan T Eppig
John P Sundberg
Publication date
01-12-2004
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 6/2004
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr930

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