Mechanisms of Intraductal Tumor Spread

摘要

During the administrative funding period of this grant we have developed a system that permits three-dimensional reconstruction of intraductal tumors (DCIS) from physical tissue sections. The system reduces the interaction required for low-resolution imaging of H AND E stained sections, registration of images of consecutive sections and annotation of tissue structures i.e. morphologically normal ducts and intraductal tumors in the images. In addition, we have developed fully automatic tools for image registration and annotation that are now being integrated in our system and used in the reconstruction of the latest tissue specimens. Complementing morphological H AND E based reconstruction, our system can be used for morphologically driven acquisition of high-resolution images from immunostained intermediate sections, both using fluorescence and brightfield microscopy. We have used our system to characterize the cellular differences between malignant transformed cells and morphologically normal cells of ducts either in continuum or in the proximity of DCIS tumors. We have looked at the distributions following markers: ER and PR status, Ki67 (proliferation). Also, software developed for this projects have been used to study the correlation between genomic instability and telomere length in breast cancer progression.