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1 Departments of Medical Oncology and 2 Biostatistics, Dana-Farber Cancer Institute, Boston, MA;
3 Department of Pathology, Brigham and Women's Hospital, Boston, MA;
4 Department of Pathology, Faulkner and Brigham and Women's Hospital, Boston, MA;
5 Department of Pathology, Beth-Israel Deaconess Medical Center, Boston, MA;
6 Harvard Medical School and 7 Harvard School of Public Health, Boston, MA;
8 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD;
9 National Cancer Institute, Bethesda, MD; and
10 Department of Pathology, Duke University Medical Center, Durham, NC
Requests for reprints: Kornelia Polyak, Dana-Farber Cancer Institute, 44 Binney St. D740C, Boston, MA 02115. Phone: (617) 632-2106; Fax: (617) 632-4005. E-mail: Kornelia_Polyak{at}dfci.harvard.edu
Gene expression patterns in ductal carcinoma in situ (DCIS), and in invasive, and metastatic breast tumors were determined using serial analysis of gene expression (SAGE). We used mRNA in situ hybridization to examine gene expression at the cellular level and immunohistochemistry on tissue microarrays to determine association between gene expression patterns and histopathologic characteristics of the tumors. We found that that the most dramatic transcriptome change occurs at the normal to DCIS transition, while there is no clear universal "in situ" or "invasive" tumor molecular signature. From the 16,430 transcripts analyzed, we identified only 5 and 11 that were preferentially up-regulated in DCIS and invasive tumors, respectively. The majority of invasive cancer specific SAGE tags correspond to novel genes. The genes we identified may define biologically and clinically meaningful subgroups of DCIS with a high risk of progression to invasive disease.
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