Department of Radiology, University of Chicago, 5841 South Maryland Avenue, MC 2026, Chicago IL 60637, USA.
Breast Cancer Res. 2009;11(5):R65. doi: 10.1186/bcr2357.
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.
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.
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.
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.
由于原位乳腺癌在小鼠模型中的体积较小，因此需要使用高分辨率成像技术来有效观察病变随时间的发展、生长和进展情况。本研究旨在使用磁共振（MR）成像技术跟踪一种人源肿瘤转基因小鼠模型中从原位肿瘤发展为浸润性癌的过程。
对 12 只发生乳腺上皮内瘤变（MIN）的 C3(1) SV40 Tag 雌性小鼠进行 MR 成像。MIN 被认为与人类导管原位癌（DCIS）相似，被认为是浸润性肿瘤的前兆。从 10 至 21 周龄每隔 2-3 周进行一次连续成像。根据 MR 图像上的形态学特征来识别 MIN 病变。随着时间的推移对病变进行随访，并测量了几个病变特征，包括体积、生长速度和形态。对于进展为浸润性癌的 MIN 病变，测量了进展时间。
总体而言，最初在 12 只小鼠中检测到 21 个 MIN 病变，平均初始体积为 0.3 ± 0.2mm3，平均生长速度为-0.15 ± 0.66 周-1。尽管所有小鼠都通过近交繁殖表达了 SV40 Tag 转基因，预计会发展为浸润性癌，但每个 MIN 病变的进展路径都大不相同：（i）9 个病变进展为浸润性肿瘤，平均进展时间为 4.6 ± 1.9 周；（ii）2 个病变消退，即在后续图像中未被检测到；（iii）5 个病变稳定超过 8 周，并且统计模型证明它们是惰性疾病。
据我们所知，这里报告的结果是首次对从原位肿瘤发展为浸润性癌的时间尺度和特征进行的测量，并提供了基于图像的证据，表明 DCIS 可能是一种非强制性的前病变，具有高度可变的结局。此外，这项研究代表了朝着开发识别可能预测哪些原位肿瘤将发展为浸润性癌而哪些不太可能进展的影像学特征的成像采集方法迈出的第一步。
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