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Human primary ductal carcinoma in situ (DCIS) subtype‐specific pathology is preserved in a mouse intraductal (MIND) xenograft model
Author(s) -
Valdez Kelli Elizabeth,
Fan Fang,
Smith William,
Allred D Craig,
Medina Daniel,
Behbod Fariba
Publication year - 2011
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2969
Subject(s) - pathology , ductal carcinoma , stroma , breast cancer , biology , carcinoma in situ , cancer , ductal cells , biopsy , carcinoma , cancer research , immunohistochemistry , medicine , genetics
Ductal carcinoma in situ (DCIS) is a non‐obligate precursor of invasive breast cancer. The current recognition that DCIS lesions exhibit inter‐ and intra‐lesion diversity suggests that the process of evolution to invasive breast cancer is more complex than previously recognized. Here we demonstrate the reproducible growth of primary DCIS cells derived from patient's surgical and biopsy samples by the mouse intraductal (MIND) model. MIND involves injection of cells into the NOD‐SCID IL2Rgamma $^{{\rm{null}}}$ (NSG) mouse mammary ducts. Twelve (eight unique and four repeats) DCIS and two atypical hyperplasia specimens, heterogeneous with respect to biomarker expression and histology, were injected into 48 mouse mammary glands and analysed for successful xenotransplantation. Overall, 14/34 and 11/14 MIND xenotransplanted glands contained human DCIS and atypical hyperplastic cells, respectively, after 8 weeks, which formed single and multi‐layered epithelium inside the ducts, and were heterogeneous with respect to expression of human cytokeratins, oestrogen receptor α (ER), and HER2. ER protein expression was recapitulated in MIND xenografts at ratios similar to the corresponding patient biopsies. In both patient biopsies and corresponding MIND xenografts, HER2 protein expression and nuclear HER2 gene overexpression were restricted to the DCIS lesions and were not found in the surrounding stroma or normal ducts. The xenografted DCIS lesions recapitulate the pathology and heterogeneity of human disease, thus providing a powerful tool for the characterization of the distinct cellular and molecular basis of inter‐ and intra‐tumoural heterogeneity and the processes of DCIS to early invasive breast cancer progression. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.