TY - JOUR
T1 - Magnetic resonance imaging of the natural history of in situ mammary neoplasia in transgenic mice
T2 - A pilot study
AU - Jansen, Sanaz A.
AU - Conzen, Suzanne D.
AU - Fan, Xiaobing
AU - Markiewicz, Erica J.
AU - Newstead, Gillian M.
AU - Karczmar, Gregory S.
N1 - Funding Information:
We would like to thank the Segal Foundation, the Florsheim Foundation, DOD predoctoral award W81XWH-06-1-0329, NIH grants P50 CA125183-01 (SPORE) and R33 CA100996-02 for financial support. In addition, we thank Brad Williams for help in obtaining the animals used in these experiments, and Lorenzo Pesce for useful discussions regarding statistical modeling.
PY - 2009/9/4
Y1 - 2009/9/4
N2 - Introduction: Because of the small size of in situ mammary cancers in mouse models, high-resolution imaging techniques are required to effectively observe how lesions develop, grow and progress over time. The purpose of this study was to use magnetic resonance (MR) imaging to track in vivo the transition from in situ neoplasia to invasive cancer in a transgenic mouse model of human cancer.Methods: MR images of 12 female C3(1) SV40 Tag mice that develop mammary intraepithelial neoplasia (MIN) were obtained. MIN is believed to be similar to human ductal carcinoma in situ (DCIS) and is considered a precursor of invasive tumors. Images were serially obtained from 10-21 weeks of age at 2-3 week intervals. MIN lesions were identified based on their morphology on MR images. Lesions were followed over time and several lesion features were measured including volume, growth rate and morphology. For those MIN lesions that progressed to invasive cancer the progression time was measured.Results: Overall, 21 MIN lesions were initially detected at an average initial volume of 0.3 ± 0.2 mm3 with an average growth rate of -0.15 ± 0.66 week-1. Even though all mice were inbred to express the SV40 Tag transgene in the mammary epithelium and expected to develop invasive carcinoma, the individual MIN lesions took vastly different progression paths: (i) 9 lesions progressed to invasive tumors with an average progression time of 4.6 ± 1.9 weeks; (ii) 2 lesions regressed, i.e., were not detected on future images; and (iii) 5 were stable for over 8 weeks, and were demonstrated by a statistical model to represent indolent disease.Conclusions: To our knowledge, the results reported here are the first measurements of the timescale and characteristics of progression from in situ neoplasia to invasive carcinoma and provide image-based evidence that DCIS may be a non-obligate precursor lesion with highly variable outcomes. In addition, this study represents a first step towards developing methods of image acquisition for identifying radiological characteristics that might predict which in situ neoplasias will become invasive cancers and which are unlikely to progress.
AB - Introduction: Because of the small size of in situ mammary cancers in mouse models, high-resolution imaging techniques are required to effectively observe how lesions develop, grow and progress over time. The purpose of this study was to use magnetic resonance (MR) imaging to track in vivo the transition from in situ neoplasia to invasive cancer in a transgenic mouse model of human cancer.Methods: MR images of 12 female C3(1) SV40 Tag mice that develop mammary intraepithelial neoplasia (MIN) were obtained. MIN is believed to be similar to human ductal carcinoma in situ (DCIS) and is considered a precursor of invasive tumors. Images were serially obtained from 10-21 weeks of age at 2-3 week intervals. MIN lesions were identified based on their morphology on MR images. Lesions were followed over time and several lesion features were measured including volume, growth rate and morphology. For those MIN lesions that progressed to invasive cancer the progression time was measured.Results: Overall, 21 MIN lesions were initially detected at an average initial volume of 0.3 ± 0.2 mm3 with an average growth rate of -0.15 ± 0.66 week-1. Even though all mice were inbred to express the SV40 Tag transgene in the mammary epithelium and expected to develop invasive carcinoma, the individual MIN lesions took vastly different progression paths: (i) 9 lesions progressed to invasive tumors with an average progression time of 4.6 ± 1.9 weeks; (ii) 2 lesions regressed, i.e., were not detected on future images; and (iii) 5 were stable for over 8 weeks, and were demonstrated by a statistical model to represent indolent disease.Conclusions: To our knowledge, the results reported here are the first measurements of the timescale and characteristics of progression from in situ neoplasia to invasive carcinoma and provide image-based evidence that DCIS may be a non-obligate precursor lesion with highly variable outcomes. In addition, this study represents a first step towards developing methods of image acquisition for identifying radiological characteristics that might predict which in situ neoplasias will become invasive cancers and which are unlikely to progress.
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U2 - 10.1186/bcr2357
DO - 10.1186/bcr2357
M3 - Article
C2 - 19732414
AN - SCOPUS:77449151124
SN - 1465-5411
VL - 11
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 5
M1 - R65
ER -