title: Determination of stromal signatures in breast carcinoma.
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.
authors.affiliation: Department of Pathology, Stanford University Medical Center, Stanford, California, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: West
authors.forename: Dimitry S A
authors.initials: DS
authors.lastname: Nuyten
authors.forename: Subbaya
authors.initials: S
authors.lastname: Subramanian
authors.forename: Torsten O
authors.initials: TO
authors.lastname: Nielsen
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Corless
authors.forename: Brian P
authors.initials: BP
authors.lastname: Rubin
authors.forename: Kelli
authors.initials: K
authors.lastname: Montgomery
authors.forename: Shirley
authors.initials: S
authors.lastname: Zhu
authors.forename: Rajiv
authors.initials: R
authors.lastname: Patel
authors.forename: Tina
authors.initials: T
authors.lastname: Hernandez-Boussard
authors.forename: John R
authors.initials: JR
authors.lastname: Goldblum
authors.forename: Patrick O
authors.initials: PO
authors.lastname: Brown
authors.forename: Marc
authors.initials: M
authors.lastname: van de Vijver
authors.forename: Matt
authors.initials: M
authors.lastname: van de Rijn
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D003937:Diagnosis, Differential; D005260:Female; D005350:Fibroma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D015999:Multivariate Analysis; D020411:Oligonucleotide Array Sequence Analysis; D012983:Soft Tissue Neoplasms / Q000235:genetics / Q000473:pathology; D017154:Stromal Cells / Q000473:pathology*
chemical_list: D018076:DNA, Complementary; D004273:DNA, Neoplasm