Mouse‐INtraDuctal (MIND): an in vivo model for studying the underlying mechanisms of DCIS malignancy
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 epithel...
Gespeichert in:
| Veröffentlicht in: | The Journal of pathology 2022-02, Vol.256 (2), p.186-201 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 201 |
|---|---|
| container_issue | 2 |
| container_start_page | 186 |
| container_title | The Journal of pathology |
| container_volume | 256 |
| creator | Hong, Yan Limback, Darlene Elsarraj, Hanan S Harper, Haleigh Haines, Haley Hansford, Hayley Ricci, Michael Kaufman, Carolyn Wedlock, Emily Xu, Mingchu Zhang, Jianhua May, Lisa Cusick, Therese Inciardi, Marc Redick, Mark Gatewood, Jason Winblad, Onalisa Aripoli, Allison Huppe, Ashley Balanoff, Christa Wagner, Jamie L Amin, Amanda L Larson, Kelsey E Ricci, Lawrence Tawfik, Ossama Razek, Hana Meierotto, Ruby O Madan, Rashna Godwin, Andrew K Thompson, Jeffrey Hilsenbeck, Susan G Futreal, Andy Thompson, Alastair Hwang, E Shelley Fan, Fang Behbod, Fariba |
| description | 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. |
| doi_str_mv | 10.1002/path.5820 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2590109143</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2590109143</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4540-b84325a8a88a5e4ebe49eca9fe839b9505d32f2d87dce8139afedbea638b391b3</originalsourceid><addsrcrecordid>eNp1kEtOwzAQQC0EgvJZcAFkiU1ZhNqxndjsqpZPJX4SsLacZNIGJU6xk6LuOAJn5CSkFFggsbJGfnqaeQgdUnJKCQkHc9PMToUMyQbqUaKiQEkVbaJe9xcGjNN4B-16_0wIUUqIbbTDeEy5ELyH8pu69fDx9j65bZwZt2ljSty_mdyOT86wsbiweFEsalzVGZQ4rx32TZstCzvFzQxwazNw5ddYQToztvCVx3WOx6PJA65MWUytselyH23lpvRw8P3uoaeL88fRVXB9dzkZDa-DlAtOgkRyFgojjZRGAIcEuILUqBwkU4kSRGQszMNMxlkKkjJlcsgSMBGTCVM0YXuov_bOXf3Sgm90VfgUytJY6A7VoVCkK0Q569DjP-hz3TrbbafDiEZxJOOId9TJmkpd7b2DXM9dURm31JToVXy9iq9X8Tv26NvYJhVkv-RP7Q4YrIHXooTl_yZ9P3y8-lJ-Akrzjww</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2616768764</pqid></control><display><type>article</type><title>Mouse‐INtraDuctal (MIND): an in vivo model for studying the underlying mechanisms of DCIS malignancy</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><creator>Hong, Yan ; Limback, Darlene ; Elsarraj, Hanan S ; Harper, Haleigh ; Haines, Haley ; Hansford, Hayley ; Ricci, Michael ; Kaufman, Carolyn ; Wedlock, Emily ; Xu, Mingchu ; Zhang, Jianhua ; May, Lisa ; Cusick, Therese ; Inciardi, Marc ; Redick, Mark ; Gatewood, Jason ; Winblad, Onalisa ; Aripoli, Allison ; Huppe, Ashley ; Balanoff, Christa ; Wagner, Jamie L ; Amin, Amanda L ; Larson, Kelsey E ; Ricci, Lawrence ; Tawfik, Ossama ; Razek, Hana ; Meierotto, Ruby O ; Madan, Rashna ; Godwin, Andrew K ; Thompson, Jeffrey ; Hilsenbeck, Susan G ; Futreal, Andy ; Thompson, Alastair ; Hwang, E Shelley ; Fan, Fang ; Behbod, Fariba</creator><creatorcontrib>Hong, Yan ; Limback, Darlene ; Elsarraj, Hanan S ; Harper, Haleigh ; Haines, Haley ; Hansford, Hayley ; Ricci, Michael ; Kaufman, Carolyn ; Wedlock, Emily ; Xu, Mingchu ; Zhang, Jianhua ; May, Lisa ; Cusick, Therese ; Inciardi, Marc ; Redick, Mark ; Gatewood, Jason ; Winblad, Onalisa ; Aripoli, Allison ; Huppe, Ashley ; Balanoff, Christa ; Wagner, Jamie L ; Amin, Amanda L ; Larson, Kelsey E ; Ricci, Lawrence ; Tawfik, Ossama ; Razek, Hana ; Meierotto, Ruby O ; Madan, Rashna ; Godwin, Andrew K ; Thompson, Jeffrey ; Hilsenbeck, Susan G ; Futreal, Andy ; Thompson, Alastair ; Hwang, E Shelley ; Fan, Fang ; Behbod, Fariba ; Grand Challenge PRECISION Consortium ; the Grand Challenge PRECISION Consortium</creatorcontrib><description>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.</description><identifier>ISSN: 0022-3417</identifier><identifier>EISSN: 1096-9896</identifier><identifier>DOI: 10.1002/path.5820</identifier><identifier>PMID: 34714554</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>animal models ; Animals ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Breast cancer ; breast malignancy ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Carcinoma, Intraductal, Noninfiltrating - genetics ; Carcinoma, Intraductal, Noninfiltrating - metabolism ; Carcinoma, Intraductal, Noninfiltrating - pathology ; Cell Movement ; Cell Proliferation ; Comedones ; DCIS ; DCIS model ; Disease Progression ; ductal carcinoma in situ ; Epithelial cells ; Epithelial Cells - metabolism ; Epithelial Cells - pathology ; Epithelial Cells - transplantation ; Female ; Heterografts ; Humans ; Malignancy ; Mammography ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Mouse‐INtraDuctal (MIND) ; Mutation ; Neoplasm Invasiveness ; Neoplasm Transplantation ; nonmalignant breast cancers ; Paraffin ; precancer biology ; Progesterone ; Receptors, Progesterone - metabolism ; Time Factors ; Xenografts</subject><ispartof>The Journal of pathology, 2022-02, Vol.256 (2), p.186-201</ispartof><rights>2021 The Authors. published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.</rights><rights>2021 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.</rights><rights>2021. This article is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4540-b84325a8a88a5e4ebe49eca9fe839b9505d32f2d87dce8139afedbea638b391b3</citedby><cites>FETCH-LOGICAL-c4540-b84325a8a88a5e4ebe49eca9fe839b9505d32f2d87dce8139afedbea638b391b3</cites><orcidid>0000-0001-6281-2651</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpath.5820$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpath.5820$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>315,782,786,1419,27931,27932,45581,45582</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34714554$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hong, Yan</creatorcontrib><creatorcontrib>Limback, Darlene</creatorcontrib><creatorcontrib>Elsarraj, Hanan S</creatorcontrib><creatorcontrib>Harper, Haleigh</creatorcontrib><creatorcontrib>Haines, Haley</creatorcontrib><creatorcontrib>Hansford, Hayley</creatorcontrib><creatorcontrib>Ricci, Michael</creatorcontrib><creatorcontrib>Kaufman, Carolyn</creatorcontrib><creatorcontrib>Wedlock, Emily</creatorcontrib><creatorcontrib>Xu, Mingchu</creatorcontrib><creatorcontrib>Zhang, Jianhua</creatorcontrib><creatorcontrib>May, Lisa</creatorcontrib><creatorcontrib>Cusick, Therese</creatorcontrib><creatorcontrib>Inciardi, Marc</creatorcontrib><creatorcontrib>Redick, Mark</creatorcontrib><creatorcontrib>Gatewood, Jason</creatorcontrib><creatorcontrib>Winblad, Onalisa</creatorcontrib><creatorcontrib>Aripoli, Allison</creatorcontrib><creatorcontrib>Huppe, Ashley</creatorcontrib><creatorcontrib>Balanoff, Christa</creatorcontrib><creatorcontrib>Wagner, Jamie L</creatorcontrib><creatorcontrib>Amin, Amanda L</creatorcontrib><creatorcontrib>Larson, Kelsey E</creatorcontrib><creatorcontrib>Ricci, Lawrence</creatorcontrib><creatorcontrib>Tawfik, Ossama</creatorcontrib><creatorcontrib>Razek, Hana</creatorcontrib><creatorcontrib>Meierotto, Ruby O</creatorcontrib><creatorcontrib>Madan, Rashna</creatorcontrib><creatorcontrib>Godwin, Andrew K</creatorcontrib><creatorcontrib>Thompson, Jeffrey</creatorcontrib><creatorcontrib>Hilsenbeck, Susan G</creatorcontrib><creatorcontrib>Futreal, Andy</creatorcontrib><creatorcontrib>Thompson, Alastair</creatorcontrib><creatorcontrib>Hwang, E Shelley</creatorcontrib><creatorcontrib>Fan, Fang</creatorcontrib><creatorcontrib>Behbod, Fariba</creatorcontrib><creatorcontrib>Grand Challenge PRECISION Consortium</creatorcontrib><creatorcontrib>the Grand Challenge PRECISION Consortium</creatorcontrib><title>Mouse‐INtraDuctal (MIND): an in vivo model for studying the underlying mechanisms of DCIS malignancy</title><title>The Journal of pathology</title><addtitle>J Pathol</addtitle><description>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.</description><subject>animal models</subject><subject>Animals</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Breast cancer</subject><subject>breast malignancy</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Carcinoma, Intraductal, Noninfiltrating - genetics</subject><subject>Carcinoma, Intraductal, Noninfiltrating - metabolism</subject><subject>Carcinoma, Intraductal, Noninfiltrating - pathology</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Comedones</subject><subject>DCIS</subject><subject>DCIS model</subject><subject>Disease Progression</subject><subject>ductal carcinoma in situ</subject><subject>Epithelial cells</subject><subject>Epithelial Cells - metabolism</subject><subject>Epithelial Cells - pathology</subject><subject>Epithelial Cells - transplantation</subject><subject>Female</subject><subject>Heterografts</subject><subject>Humans</subject><subject>Malignancy</subject><subject>Mammography</subject><subject>Mice</subject><subject>Mice, Inbred NOD</subject><subject>Mice, SCID</subject><subject>Mouse‐INtraDuctal (MIND)</subject><subject>Mutation</subject><subject>Neoplasm Invasiveness</subject><subject>Neoplasm Transplantation</subject><subject>nonmalignant breast cancers</subject><subject>Paraffin</subject><subject>precancer biology</subject><subject>Progesterone</subject><subject>Receptors, Progesterone - metabolism</subject><subject>Time Factors</subject><subject>Xenografts</subject><issn>0022-3417</issn><issn>1096-9896</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNp1kEtOwzAQQC0EgvJZcAFkiU1ZhNqxndjsqpZPJX4SsLacZNIGJU6xk6LuOAJn5CSkFFggsbJGfnqaeQgdUnJKCQkHc9PMToUMyQbqUaKiQEkVbaJe9xcGjNN4B-16_0wIUUqIbbTDeEy5ELyH8pu69fDx9j65bZwZt2ljSty_mdyOT86wsbiweFEsalzVGZQ4rx32TZstCzvFzQxwazNw5ddYQToztvCVx3WOx6PJA65MWUytselyH23lpvRw8P3uoaeL88fRVXB9dzkZDa-DlAtOgkRyFgojjZRGAIcEuILUqBwkU4kSRGQszMNMxlkKkjJlcsgSMBGTCVM0YXuov_bOXf3Sgm90VfgUytJY6A7VoVCkK0Q569DjP-hz3TrbbafDiEZxJOOId9TJmkpd7b2DXM9dURm31JToVXy9iq9X8Tv26NvYJhVkv-RP7Q4YrIHXooTl_yZ9P3y8-lJ-Akrzjww</recordid><startdate>202202</startdate><enddate>202202</enddate><creator>Hong, Yan</creator><creator>Limback, Darlene</creator><creator>Elsarraj, Hanan S</creator><creator>Harper, Haleigh</creator><creator>Haines, Haley</creator><creator>Hansford, Hayley</creator><creator>Ricci, Michael</creator><creator>Kaufman, Carolyn</creator><creator>Wedlock, Emily</creator><creator>Xu, Mingchu</creator><creator>Zhang, Jianhua</creator><creator>May, Lisa</creator><creator>Cusick, Therese</creator><creator>Inciardi, Marc</creator><creator>Redick, Mark</creator><creator>Gatewood, Jason</creator><creator>Winblad, Onalisa</creator><creator>Aripoli, Allison</creator><creator>Huppe, Ashley</creator><creator>Balanoff, Christa</creator><creator>Wagner, Jamie L</creator><creator>Amin, Amanda L</creator><creator>Larson, Kelsey E</creator><creator>Ricci, Lawrence</creator><creator>Tawfik, Ossama</creator><creator>Razek, Hana</creator><creator>Meierotto, Ruby O</creator><creator>Madan, Rashna</creator><creator>Godwin, Andrew K</creator><creator>Thompson, Jeffrey</creator><creator>Hilsenbeck, Susan G</creator><creator>Futreal, Andy</creator><creator>Thompson, Alastair</creator><creator>Hwang, E Shelley</creator><creator>Fan, Fang</creator><creator>Behbod, Fariba</creator><general>John Wiley & Sons, Ltd</general><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>WIN</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-6281-2651</orcidid></search><sort><creationdate>202202</creationdate><title>Mouse‐INtraDuctal (MIND): an in vivo model for studying the underlying mechanisms of DCIS malignancy</title><author>Hong, Yan ; Limback, Darlene ; Elsarraj, Hanan S ; Harper, Haleigh ; Haines, Haley ; Hansford, Hayley ; Ricci, Michael ; Kaufman, Carolyn ; Wedlock, Emily ; Xu, Mingchu ; Zhang, Jianhua ; May, Lisa ; Cusick, Therese ; Inciardi, Marc ; Redick, Mark ; Gatewood, Jason ; Winblad, Onalisa ; Aripoli, Allison ; Huppe, Ashley ; Balanoff, Christa ; Wagner, Jamie L ; Amin, Amanda L ; Larson, Kelsey E ; Ricci, Lawrence ; Tawfik, Ossama ; Razek, Hana ; Meierotto, Ruby O ; Madan, Rashna ; Godwin, Andrew K ; Thompson, Jeffrey ; Hilsenbeck, Susan G ; Futreal, Andy ; Thompson, Alastair ; Hwang, E Shelley ; Fan, Fang ; Behbod, Fariba</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4540-b84325a8a88a5e4ebe49eca9fe839b9505d32f2d87dce8139afedbea638b391b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>animal models</topic><topic>Animals</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Breast cancer</topic><topic>breast malignancy</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - pathology</topic><topic>Carcinoma, Intraductal, Noninfiltrating - genetics</topic><topic>Carcinoma, Intraductal, Noninfiltrating - metabolism</topic><topic>Carcinoma, Intraductal, Noninfiltrating - pathology</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Comedones</topic><topic>DCIS</topic><topic>DCIS model</topic><topic>Disease Progression</topic><topic>ductal carcinoma in situ</topic><topic>Epithelial cells</topic><topic>Epithelial Cells - metabolism</topic><topic>Epithelial Cells - pathology</topic><topic>Epithelial Cells - transplantation</topic><topic>Female</topic><topic>Heterografts</topic><topic>Humans</topic><topic>Malignancy</topic><topic>Mammography</topic><topic>Mice</topic><topic>Mice, Inbred NOD</topic><topic>Mice, SCID</topic><topic>Mouse‐INtraDuctal (MIND)</topic><topic>Mutation</topic><topic>Neoplasm Invasiveness</topic><topic>Neoplasm Transplantation</topic><topic>nonmalignant breast cancers</topic><topic>Paraffin</topic><topic>precancer biology</topic><topic>Progesterone</topic><topic>Receptors, Progesterone - metabolism</topic><topic>Time Factors</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hong, Yan</creatorcontrib><creatorcontrib>Limback, Darlene</creatorcontrib><creatorcontrib>Elsarraj, Hanan S</creatorcontrib><creatorcontrib>Harper, Haleigh</creatorcontrib><creatorcontrib>Haines, Haley</creatorcontrib><creatorcontrib>Hansford, Hayley</creatorcontrib><creatorcontrib>Ricci, Michael</creatorcontrib><creatorcontrib>Kaufman, Carolyn</creatorcontrib><creatorcontrib>Wedlock, Emily</creatorcontrib><creatorcontrib>Xu, Mingchu</creatorcontrib><creatorcontrib>Zhang, Jianhua</creatorcontrib><creatorcontrib>May, Lisa</creatorcontrib><creatorcontrib>Cusick, Therese</creatorcontrib><creatorcontrib>Inciardi, Marc</creatorcontrib><creatorcontrib>Redick, Mark</creatorcontrib><creatorcontrib>Gatewood, Jason</creatorcontrib><creatorcontrib>Winblad, Onalisa</creatorcontrib><creatorcontrib>Aripoli, Allison</creatorcontrib><creatorcontrib>Huppe, Ashley</creatorcontrib><creatorcontrib>Balanoff, Christa</creatorcontrib><creatorcontrib>Wagner, Jamie L</creatorcontrib><creatorcontrib>Amin, Amanda L</creatorcontrib><creatorcontrib>Larson, Kelsey E</creatorcontrib><creatorcontrib>Ricci, Lawrence</creatorcontrib><creatorcontrib>Tawfik, Ossama</creatorcontrib><creatorcontrib>Razek, Hana</creatorcontrib><creatorcontrib>Meierotto, Ruby O</creatorcontrib><creatorcontrib>Madan, Rashna</creatorcontrib><creatorcontrib>Godwin, Andrew K</creatorcontrib><creatorcontrib>Thompson, Jeffrey</creatorcontrib><creatorcontrib>Hilsenbeck, Susan G</creatorcontrib><creatorcontrib>Futreal, Andy</creatorcontrib><creatorcontrib>Thompson, Alastair</creatorcontrib><creatorcontrib>Hwang, E Shelley</creatorcontrib><creatorcontrib>Fan, Fang</creatorcontrib><creatorcontrib>Behbod, Fariba</creatorcontrib><creatorcontrib>Grand Challenge PRECISION Consortium</creatorcontrib><creatorcontrib>the Grand Challenge PRECISION Consortium</creatorcontrib><collection>Wiley Online Library (Open Access Collection)</collection><collection>Wiley Online Library (Open Access Collection)</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hong, Yan</au><au>Limback, Darlene</au><au>Elsarraj, Hanan S</au><au>Harper, Haleigh</au><au>Haines, Haley</au><au>Hansford, Hayley</au><au>Ricci, Michael</au><au>Kaufman, Carolyn</au><au>Wedlock, Emily</au><au>Xu, Mingchu</au><au>Zhang, Jianhua</au><au>May, Lisa</au><au>Cusick, Therese</au><au>Inciardi, Marc</au><au>Redick, Mark</au><au>Gatewood, Jason</au><au>Winblad, Onalisa</au><au>Aripoli, Allison</au><au>Huppe, Ashley</au><au>Balanoff, Christa</au><au>Wagner, Jamie L</au><au>Amin, Amanda L</au><au>Larson, Kelsey E</au><au>Ricci, Lawrence</au><au>Tawfik, Ossama</au><au>Razek, Hana</au><au>Meierotto, Ruby O</au><au>Madan, Rashna</au><au>Godwin, Andrew K</au><au>Thompson, Jeffrey</au><au>Hilsenbeck, Susan G</au><au>Futreal, Andy</au><au>Thompson, Alastair</au><au>Hwang, E Shelley</au><au>Fan, Fang</au><au>Behbod, Fariba</au><aucorp>Grand Challenge PRECISION Consortium</aucorp><aucorp>the Grand Challenge PRECISION Consortium</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mouse‐INtraDuctal (MIND): an in vivo model for studying the underlying mechanisms of DCIS malignancy</atitle><jtitle>The Journal of pathology</jtitle><addtitle>J Pathol</addtitle><date>2022-02</date><risdate>2022</risdate><volume>256</volume><issue>2</issue><spage>186</spage><epage>201</epage><pages>186-201</pages><issn>0022-3417</issn><eissn>1096-9896</eissn><abstract>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.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>34714554</pmid><doi>10.1002/path.5820</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0001-6281-2651</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-3417 |
| ispartof | The Journal of pathology, 2022-02, Vol.256 (2), p.186-201 |
| issn | 0022-3417 1096-9896 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2590109143 |
| source | MEDLINE; Access via Wiley Online Library |
| subjects | animal models Animals Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Breast cancer breast malignancy Breast Neoplasms - genetics Breast Neoplasms - metabolism Breast Neoplasms - pathology Carcinoma, Intraductal, Noninfiltrating - genetics Carcinoma, Intraductal, Noninfiltrating - metabolism Carcinoma, Intraductal, Noninfiltrating - pathology Cell Movement Cell Proliferation Comedones DCIS DCIS model Disease Progression ductal carcinoma in situ Epithelial cells Epithelial Cells - metabolism Epithelial Cells - pathology Epithelial Cells - transplantation Female Heterografts Humans Malignancy Mammography Mice Mice, Inbred NOD Mice, SCID Mouse‐INtraDuctal (MIND) Mutation Neoplasm Invasiveness Neoplasm Transplantation nonmalignant breast cancers Paraffin precancer biology Progesterone Receptors, Progesterone - metabolism Time Factors Xenografts |
| title | Mouse‐INtraDuctal (MIND): an in vivo model for studying the underlying mechanisms of DCIS malignancy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-04T13%3A12%3A47IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Mouse%E2%80%90INtraDuctal%20(MIND):%20an%20in%20vivo%20model%20for%20studying%20the%20underlying%20mechanisms%20of%20DCIS%20malignancy&rft.jtitle=The%20Journal%20of%20pathology&rft.au=Hong,%20Yan&rft.aucorp=Grand%20Challenge%20PRECISION%20Consortium&rft.date=2022-02&rft.volume=256&rft.issue=2&rft.spage=186&rft.epage=201&rft.pages=186-201&rft.issn=0022-3417&rft.eissn=1096-9896&rft_id=info:doi/10.1002/path.5820&rft_dat=%3Cproquest_cross%3E2590109143%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2616768764&rft_id=info:pmid/34714554&rfr_iscdi=true |