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.
Subject(s)
Breast Neoplasms/pathology , Carcinoma, Intraductal, Noninfiltrating/pathology , Epithelial Cells/pathology , Animals , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Carcinoma, Intraductal, Noninfiltrating/genetics , Carcinoma, Intraductal, Noninfiltrating/metabolism , Cell Movement , Cell Proliferation , Disease Progression , Epithelial Cells/metabolism , Epithelial Cells/transplantation , Female , Heterografts , Humans , Mice, Inbred NOD , Mice, SCID , Mutation , Neoplasm Invasiveness , Neoplasm Transplantation , Receptors, Progesterone/metabolism , Time FactorsABSTRACT
PURPOSE: Gender and sexually diverse adolescents and young adults in Baltimore City, Maryland, are disproportionately impacted by HIV. The Virtual and Online Integrated Sexual Health Services for Youth program is a health navigation program which combines virtual sexual health service delivery and health navigation to link youth at risk for HIV acquisition to HIV testing/prevention and sexual healthcare services. METHODS: Youth between 13 and 26 years old and residing in the Baltimore area were eligible to participate in the program. Demographic and engagement data from 238 youth (average age 21.4, SD = 2.5) who requested navigation were collected and recorded in a Health Insurance Portability and Accountability Act (HIPAA)-secure medical database and examined for associations between demographics, referral source, and the number of navigational services to which they were linked. Focused populations were defined as residents of high HIV prevalence zip codes who identify as sexual and gender diverse youth. RESULTS: Receipt of navigational services was significantly associated with self-identifying as sexually diverse. A multivariate regression revealed a significant association between the count of navigational services a youth was linked to and recording one's sexual orientation, identifying as a cisgender male, and residing in a high HIV-prevalence zip code. DISCUSSION: Virtual health navigation has the potential to engage priority populations, including sexual and gender diverse youth. By refining linkage and identification approaches to health navigation, future outreach attempts can be tailored to support vulnerable communities, with the potential to improve sexual healthcare access.