title: Variations in stromal signatures in breast and colorectal cancer metastases.
abstract: The tumour microenvironment (TME) plays an important role in tumour survival and growth, but little is known about the degree of preservation between different stromal response patterns found in primary tumours and their metastases. We have previously identified gene expression profiles for two distinct stromal signatures in breast carcinoma of fibroblast (aka DTF) and macrophage (aka CSF1) response and found them to be correlated with clinicopathological features, including outcome. In this study, we compare the DTF fibroblast and CSF1 macrophage stromal response patterns in primary breast and colorectal cancers to their matched lymph node metastases. In both breast and colorectal cancer, there was a significant positive correlation between the CSF1 macrophage signature in the primary tumours and the matched lymph node metastases, as assessed by immunohistochemical markers. No such correlation was observed for the DTF fibroblast signature. A similar result was seen in independent analysis of two published gene expression microarray datasets. The variations of these stromal reaction patterns from the primary to the metastasis shed light on the relationship between the neoplastic cells and the non-neoplastic cells in the TME. The preservation of the CSF1 macrophage response pattern in metastases lends support to targeting the CSF1 pathway in cancer.
authors.affiliation: Department of Pathology, Stanford University Medical Center, Stanford, CA, USA.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Webster
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Beck
authors.forename: Mimansa
authors.initials: M
authors.lastname: Sharma
authors.forename: Inigo
authors.initials: I
authors.lastname: Espinosa
authors.forename: Britta
authors.initials: B
authors.lastname: Weigelt
authors.forename: Marthe
authors.initials: M
authors.lastname: Schreuder
authors.forename: Kelli D
authors.initials: KD
authors.lastname: Montgomery
authors.forename: Kristin C
authors.initials: KC
authors.lastname: Jensen
authors.forename: Matt
authors.initials: M
authors.lastname: van de Rijn
authors.forename: Robert
authors.initials: R
authors.lastname: West
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000556:secondary; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D017154:Stromal Cells / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D016173:Macrophage Colony-Stimulating Factor