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Intraductal patient‐derived xenografts of estrogen receptor α‐positive (ER+) breast cancer recapitulate the histopathological spectrum and metastatic potential of human lesions

Abstract : Estrogen receptor  positive (ER+) or “luminal” breast cancers (BC) were notoriously difficult to establish as patient-derived xenografts (PDXs). We and others recently demonstrated that the microenvironment is critical for ER+ tumor cells; when grafted as single cells into milk ducts of NOD Scid gamma (NSG) females >90% of ER+ tumors can be established as xenografts and recapitulate many features of the human disease in vivo. This intra-ductal (ID) 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+ ID-PDXs histopathologically. We find that ID-PDXs vary in extent and define four histopathological patterns: flat, lobular, in situ, and invasive, which occur in pure and combined forms. The ID-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+ breast cancer and raise the intriguing possibility that tumor cell dissemination may occur earlier than currently thought.
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https://hal.univ-reims.fr/hal-02431932
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Submitted on : Wednesday, June 10, 2020 - 3:20:34 PM
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Maryse Fiche, Valentina Scabia, Patrick Aouad, Laura Battista, Assia Treboux, et al.. Intraductal patient‐derived xenografts of estrogen receptor α‐positive (ER+) breast cancer recapitulate the histopathological spectrum and metastatic potential of human lesions. Journal of Pathology, Wiley, 2019, 247 (3), pp.287-292. ⟨10.1002/path.5200⟩. ⟨hal-02431932⟩

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