Intraductal patient-derived xenografts of estrogen receptor α-positive breast cancer recapitulate the histopathological spectrum and metastatic potential of human lesions.
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Date
2019-03-01ICR Author
Author
Fiche, M
Scabia, V
Aouad, P
Battista, L
Treboux, A
Stravodimou, A
Zaman, K
RLS,
Dormoy, V
Ayyanan, A
Sflomos, G
Brisken, C
Type
Journal Article
Metadata
Show full item recordAbstract
Estrogen receptor α-positive (ER-positive) or 'luminal' breast cancers were notoriously difficult to establish as patient-derived xenografts (PDXs). We and others recently demonstrated that the microenvironment is critical for ER-positive tumor cells; when grafted as single cells into milk ducts of NOD Scid gamma females, >90% of ER-positive tumors can be established as xenografts and recapitulate many features of the human disease in vivo. This intraductal approach holds promise for personalized medicine, yet human and murine stroma are organized differently and this and other species specificities may limit the value of this model. Here, we analyzed 21 ER-positive intraductal PDXs histopathologically. We found that intraductal PDXs vary in extent and define four histopathological patterns: flat, lobular, in situ and invasive, which occur in pure and combined forms. The intraductal PDXs replicate earlier stages of tumor development than their clinical counterparts. Micrometastases are already detected when lesions appear in situ. Tumor extent, histopathological patterns and micrometastatic load correlate with biological properties of their tumors of origin. Our findings add evidence to the validity of the intraductal model for in vivo studies of ER-positive breast cancer and raise the intriguing possibility that tumor cell dissemination may occur earlier than currently thought. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Collections
Subject
RLS
Animals
Humans
Mice, SCID
Carcinoma, Intraductal, Noninfiltrating
Breast Neoplasms
Mammary Neoplasms, Experimental
Estrogen Receptor alpha
Neoplasm Transplantation
Female
Neoplasm Micrometastasis
Heterografts
Research team
Endocrine control mechanisms
Language
eng
Date accepted
2018-11-08
License start date
2019-03
Citation
The Journal of pathology, 2019, 247 (3), pp. 287 - 292
Publisher
WILEY