Determination of stromal signatures in breast carcinoma |
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Authors: | West Robert B Nuyten Dimitry S A Subramanian Subbaya Nielsen Torsten O Corless Christopher L Rubin Brian P Montgomery Kelli Zhu Shirley Patel Rajiv Hernandez-Boussard Tina Goldblum John R Brown Patrick O van de Vijver Marc van de Rijn Matt |
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Institution: | 1
Department of Pathology, Stanford University Medical Center
Stanford, California
United States of America;2
Division of Diagnostic Oncology, Netherlands Cancer Institute
Amsterdam
the Netherlands;3
Department of Pathology and Genetic Pathology Evaluation Centre, Vancouver General Hospital
Vancouver BC
United States of America;4
Department of Pathology and OHSU Cancer Institute, Oregon Health and Science University
Portland, Oregon
United States of America;5
Department of Anatomic Pathology, University of Washington Medical Center
Seattle, Washington
United States of America;6
Department of Pathology and Laboratory Medicine, Emory University School of Medicine
Atlanta, Georgia
United States of America;7
Department of Biochemistry, Stanford University Medical Center
Stanford, California
United States of America;8
Department of Anatomic Pathology, Cleveland Clinic Foundation
Cleveland, Ohio
United States of America;9
Deparment of Biochemistry and Howard Hughes Medical Institute, Stanford University Medical Center
Stanford, California
United States of America;National Cancer Institute
United States of America |
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Abstract: | Many soft tissue tumors recapitulate features of normal connective tissue. We hypothesize that different types of fibroblastic tumors are representative of different populations of fibroblastic cells or different activation states of these cells. We examined two tumors with fibroblastic features, solitary fibrous tumor (SFT) and desmoid-type fibromatosis (DTF), by DNA microarray analysis and found that they have very different expression profiles, including significant differences in their patterns of expression of extracellular matrix genes and growth factors. Using immunohistochemistry and in situ hybridization on a tissue microarray, we found that genes specific for these two tumors have mutually specific expression in the stroma of nonneoplastic tissues. We defined a set of 786 gene spots whose pattern of expression distinguishes SFT from DTF. In an analysis of DNA microarray gene expression data from 295 previously published breast carcinomas, we found that expression of this gene set defined two groups of breast carcinomas with significant differences in overall survival. One of the groups had a favorable outcome and was defined by the expression of DTF genes. The other group of tumors had a poor prognosis and showed variable expression of genes enriched for SFT type. Our findings suggest that the host stromal response varies significantly among carcinomas and that gene expression patterns characteristic of soft tissue tumors can be used to discover new markers for normal connective tissue cells. |
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