High and low mammographic density human breast tissues maintain histological differential in murine tissue engineering chambers

Chew, G.L., Huang, D., Lin, S.J., Huo, C., Blick, T., Henderson, M.A., Hill, P., Cawson, J., Morrison, W.A., Campbell, I.G., Hopper, J.L., Southey, M.C., Haviv, I., & Thompson, E.W. (2012) High and low mammographic density human breast tissues maintain histological differential in murine tissue engineering chambers. Breast Cancer Research and Treatment, 135(1), pp. 177-187.

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Abstract

Mammographic density (MD) is the area of breast tissue that appears radiologically white on mammography. Although high MD is a strong risk factor for breast cancer, independent of BRCA1/2 mutation status, the molecular basis of high MD and its associated breast cancer risk is poorly understood. MD studies will benefit from an animal model, where hormonal, gene and drug perturbations on MD can be measured in a preclinical context. High and low MD tissues were selectively sampled by stereotactic biopsy from operative specimens of high-risk women undergoing prophylactic mastectomy. The high and low MD tissues were transferred into separate vascularised biochambers in the groins of SCID mice. Chamber material was harvested after 6 weeks for histological analyses and immunohistochemistry for cytokeratins, vimentin and a human-specific mitochondrial antigen. Within-individual analysis was performed in replicate mice, eliminating confounding by age, body mass index and process-related factors, and comparisons were made to the parental human tissue. Maintenance of differential MD post-propagation was assessed radiographically. Immunohistochemical staining confirmed the preservation of human glandular and stromal components in the murine biochambers, with maintenance of radiographic MD differential. Propagated high MD regions had higher stromal (p = 0.0002) and lower adipose (p = 0.0006) composition, reflecting the findings in the original human breast tissue, although glands appeared small and non-complex in both high and low MD groups. No significant differences were observed in glandular area (p = 0.4) or count (p = 0.4) between high and low MD biochamber tissues. Human mammary glandular and stromal tissues were viably maintained in murine biochambers, with preservation of differential radiographic density and histological features. Our study provides a murine model for future studies into the biomolecular basis of MD as a risk factor for breast cancer.

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7 citations in Web of Science®

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ID Code: 71740
Item Type: Journal Article
Refereed: Yes
Additional Information: Cited By (since 1996):1
Export Date: 6 May 2014
Source: Scopus
PubMed ID: 22729891
Additional URLs:
Keywords: Bioengineering chambers, Breast density, Mammographic density, Murine, Stroma
DOI: 10.1007/s10549-012-2128-z
ISSN: 1573-7217
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Deposited On: 16 May 2014 03:39
Last Modified: 19 May 2014 01:49

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