Abstract
Abstract Background: Atypical ductal hyperplasia (ADH) is a premalignant breast lesion associated with an increased risk of breast cancer which shares some but not all the features of ductal carcinoma in situ (DCIS). The mechanism that ADH changes to DCIS and even invasive ductal carcinoma (IDC) is still not clear now. There is a pressing need to develop screening techniques that are accurate, minimally invasive and, more sensitive to identify early neoplastic changes and hence improve early breast cancer diagnosis. Our aim was to explore the differences and relationships between normal, ADH, DCIS and IDC lesions of the breast based on biochemical characteristics determined by Raman spectroscopy Methods: Frozen sections were collected from 39 patients (all ladies) who underwent surgical resection or mammotome biopsy at the Department of Breast Surgery, the First Hospital of Jilin University. After operation the samples were immediately frozen at -20-25 ° and two contiguous sections (6 µm thickness) were cut from a sample by freezing microtome. One was stained with haematoxylin and eosin for routine histopathological analysis; the same position of the other section was detected by Microscopic confocal Raman spectrometer (HORIBA JY Lab800, 633nm) with its mirror image (the H&E section). After Raman measurement, the sections were routinely processed, stained with H&E and histologically examined. Support vector machine (SVM) was used to differentiate different breast lesions. Results: A total of 475 Raman spectra were obtained from 9 normal breast tissues, 7 ADH, 8 DCIS, and 15 IDC breast tissues. Pronounced mean Raman spectra differences were observed between normal tissues, ADH, DCIS and IDC tissues. The significant features of normal tissues are 1301, 1438, 1652, and 1743 cm-1, these peak positions are attributed to lipids, and the spectra profiles of normal tissues have no strong protein peaks. Most noticeable was the increased protein and reduced lipid levels of ADH tissues compared to normal tissues. The peak relative intensity of 1158 cm-1 which is attributed to the vibrational modes of C-C stretch of proteins has significantly increased from normal tissues to DCIS and IDC in breast. The major spectra differences in ADH, DCIS and IDC spectra were evidenced by a red shift with a broad peak of CH2, the intensity of the stretching vibration peak of carotenoids, a relatively strong band of amide-I, and the nuclear acid peak. ADH tissues had the largest constituent variations between subjects. During the disease progression, IDC tissues have smaller inter-subject constituent variations than DCIS and ADH tissues. The accuracies of SVM are 93% and 95% in discriminating normal and IDC, while only 50% and 51% in discriminating ADH and DCIS. Conclusion: Malignant transformations in tissue are associated with complex biochemical changes and may provide an effective way to evaluate the malignancy by Raman spectroscopy as it reveals differences between normal tissues, ADH, DCIS and IDC tissues in the breast. Further study to explain the biochemical relationships between these differences will shed more light into a better understanding of the mechanism by which ADH and DCIS convert to IDC. Citation Format: Bing Han, Haipeng Zhang, Chao Zheng, Ye Du, Lijia Liang, Weiqing Xu, Zhimin Fan. Explore the differences and relationships between normal and ADH, DCIS and IDC tissues in breast based on Raman spectroscopy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-05-10.
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