Activation of host wound responses in breast cancer microenvironment.
OBJECTIVE
Cancer progression is mediated by processes that are also important in wound repair. As a result, cancers have been conceptualized as overhealing wounds or "wounds that do not heal," and gene expression signatures reflective of wound repair have shown value as predictors of breast cancer survival. Despite the widespread acknowledgment of commonalities between host responses to wounds and host responses to cancer, the gene expression responses of normal tissue adjacent to cancers have not been well characterized.


METHODS
Using RNA extracted from histologically normal breast tissue from 107 patients, including 60 reduction mammoplasty patients and 47 cancer patients, we measured whole genome expression profiles and identified a gene expression signature that is induced in response to breast cancer.


RESULTS
This signature represents an in vivo "wound response" signature that is differentially expressed in the normal tissue of breast cancer patients compared with those without disease and is highly accurate (at least 92% sensitivity and 98% specificity) in distinguishing diseased and nondiseased. The in vivo wound response signature is highly prognostic of breast cancer survival, and there is a strong association between the groups identified by this signature and those identified using serum-treated fibroblasts and other microenvironment-derived or microenvironment-related signatures.


CONCLUSIONS
The prevalence of the wound response signature in histologically normal tissue adjacent to breast cancer suggests that microenvironment response is an important variable in breast cancer progression and may be an important target for clinical interventions.
Troester
Melissa A
MA
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. troester@unc.edu
Lee
Myung Hee
MH
Carter
Matthew
M
Fan
Cheng
C
Cowan
David W
DW
Perez
Erick Roman
ER
Pirone
Jason R
JR
Perou
Charles M
CM
Jerry
D Joseph
DJ
Schneider
Sallie Smith
SS
D001940:Breast / Q000473:pathology / Q000601:surgery; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D051546:Cyclooxygenase 2 / Q000378:metabolism; D055515:Cysteine-Rich Protein 61 / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016462:Mammaplasty; D009389:Neovascularization, Pathologic; D015203:Reproducibility of Results; D014945:Wound Healing
C501848:CCN1 protein, human; D055515:Cysteine-Rich Protein 61; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human