Mouse-INtraDuctal (MIND): an in vivo model for studying the underlying mechanisms of DCIS malignancy
Por:
Hong Y., Limback D., Elsarraj H.S., Harper H., Haines H., Hansford H., Ricci M., Kaufman C., Wedlock E., Xu M., Zhang J., May L., Cusick T., Inciardi M., Redick M., Gatewood J., Winblad O., Aripoli A., Huppe A., Balanoff C., Wagner J.L., Amin A.L., Larson K.E., Ricci L., Tawfik O., Razek H., Meierotto R.O., Madan R., Godwin A.K., Thompson J., Hilsenbeck S.G., Futreal A., Thompson A., Hwang E.S., Fan F., Behbod F.
Publicada:
1 ene 2022
Categoría:
Pathology and forensic medicine
Resumen:
Due to widespread adoption of screening mammography, there has been a significant increase in new diagnoses of ductal carcinoma in situ (DCIS). However, DCIS prognosis remains unclear. To address this gap, we developed an in vivo model, Mouse-INtraDuctal (MIND), in which patient-derived DCIS epithelial cells are injected intraductally and allowed to progress naturally in mice. Similar to human DCIS, the cancer cells formed in situ lesions inside the mouse mammary ducts and mimicked all histologic subtypes including micropapillary, papillary, cribriform, solid, and comedo. Among 37 patient samples injected into 202 xenografts, at median duration of 9 months, 20 samples (54%) injected into 95 xenografts showed in vivo invasive progression, while 17 (46%) samples injected into 107 xenografts remained non-invasive. Among the 20 samples that showed invasive progression, nine samples injected into 54 xenografts exhibited a mixed pattern in which some xenografts showed invasive progression while others remained non-invasive. Among the clinically relevant biomarkers, only elevated progesterone receptor expression in patient DCIS and the extent of in vivo growth in xenografts predicted an invasive outcome. The Tempus XT assay was used on 16 patient DCIS formalin-fixed, paraffin-embedded sections including eight DCISs that showed invasive progression, five DCISs that remained non-invasive, and three DCISs that showed a mixed pattern in the xenografts. Analysis of the frequency of cancer-related pathogenic mutations among the groups showed no significant differences (KW: p > 0.05). There were also no differences in the frequency of high, moderate, or low severity mutations (KW; p > 0.05). These results suggest that genetic changes in the DCIS are not the primary driver for the development of invasive disease. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Filiaciones:
Hong Y.:
Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS, United States
Limback D.:
Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS, United States
Elsarraj H.S.:
Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS, United States
Harper H.:
University of Kansas School of Medicine, The University of Kansas Medical Center, Kansas City, KS, United States
Haines H.:
Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS, United States
Hansford H.:
Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS, United States
Ricci M.:
Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS, United States
Kaufman C.:
University of Kansas School of Medicine, The University of Kansas Medical Center, Kansas City, KS, United States
Wedlock E.:
Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS, United States
Xu M.:
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
Zhang J.:
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
May L.:
Department of Radiology, The University of Kansas School of Medicine-Wichita, Wichita, KS, United States
Cusick T.:
Department of Surgery, The University of Kansas School of Medicine-Wichita, Wichita, KS, United States
Inciardi M.:
Department of Radiology, The University of Kansas Medical Center, Kansas City, KS, United States
Redick M.:
Department of Radiology, The University of Kansas Medical Center, Kansas City, KS, United States
Gatewood J.:
Department of Radiology, The University of Kansas Medical Center, Kansas City, KS, United States
Winblad O.:
Department of Radiology, The University of Kansas Medical Center, Kansas City, KS, United States
Aripoli A.:
Department of Radiology, The University of Kansas Medical Center, Kansas City, KS, United States
Huppe A.:
Department of Radiology, The University of Kansas Medical Center, Kansas City, KS, United States
Balanoff C.:
Department of General Surgery, Breast Surgical Oncology Division, The University of Kansas Medical Center, Kansas City, KS, United States
Wagner J.L.:
Department of General Surgery, Breast Surgical Oncology Division, The University of Kansas Medical Center, Kansas City, KS, United States
Amin A.L.:
Department of General Surgery, Breast Surgical Oncology Division, The University of Kansas Medical Center, Kansas City, KS, United States
Larson K.E.:
Department of General Surgery, Breast Surgical Oncology Division, The University of Kansas Medical Center, Kansas City, KS, United States
Ricci L.:
Department of Radiology, Truman Medical Center, Kansas City, MO, United States
Tawfik O.:
Department of Pathology, St Luke's Health System of Kansas City, MAWD Pathology Group, Kansas City, MO, United States
Razek H.:
Heartland Pathology, Wichita, KS, United States
Meierotto R.O.:
Breast Radiology, Saint Luke's Cancer Institute, Saint Luke's Health System, Kansas City, MO, United States
Madan R.:
Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS, United States
Godwin A.K.:
Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS, United States
Thompson J.:
Department of Biostatistics, The University of Kansas Medical Center, Kansas City, KS, United States
Hilsenbeck S.G.:
Lester and Sue Smith Breast Center, Biostatistics and Informatics Shared Resources, Duncan Cancer Center, Baylor College of Medicine, Houston, TX, United States
Futreal A.:
Department of Genomic Medicine, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
Thompson A.:
Section of Breast Surgery, Baylor College of Medicine, Lester and Sue Smith Breast Center, Dan L Duncan Comprehensive Cancer Center, Houston, TX, United States
Hwang E.S.:
Duke University Department of Surgery, Durham, NC, United States
Fan F.:
Department of Pathology, City of Hope Medical Center, Duarte, CA, United States
Behbod F.:
Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS, United States
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