Variations in Stromal Signatures in Breast Cancer Metastases
JA Webster, AH Beck, M Sharma, I Espinosa, M Schreuder, KD Montgomery, KC Jensen, M van de Rijn, RB West. Stanford University, Stanford, CA; Palo Alto Veterans Administration Hospital, Palo Alto, CA
Background: The tumor microenvironment (TME) plays an important role in tumor survival and growth but little is known about the degree of preservation between different stromal response patterns found in primary tumors and their metastases. We have previously identified gene signatures for two distinct stromal response patterns in breast carcinoma of fibroblast (aka DTF) and macrophage response (aka CSF1) and found them to be correlated with clinicopathologic features including outcome.
Design: To determine whether this signature is conserved between primaries and metastases, we examined the DTF fibroblast and CSF1 macrophage response signatures between matched breast cancer primary and metastases on 49 cases and matched colon cancer primary and metastases on 15 cases, all represented on a tissue microarray. Four previously established markers (FCGR3a, FCGR2a, CTSL1, and CD163) were used for the CSF1 macrophage response and 5 five markers (SPARC, VCAN, CDH11, SDC1 and MMP11), derived from the core gene set of the DTF fibroblast stromal signature, were used for the DTF fibroblast stromal signature. To validate our immunohistochemistry findings, we examined the stromal signatures in a gene expression profiling data set using published gene expression microarray data from a study comparing 15 primary breast tumors and their matched lymph node metastases.
Results: In both breast and colorectal cancer, there was a significant, positive correlation between the CSF1 macrophage signature in the primary tumors and the matched lymph node metastases as assessed by immunohistochemical markers. No such correlation was observed for the DTF fibroblast signature. The CSF1 macrophage positive correlation was confirmed by analysis of the gene expression microarray dataset of 15 primary and matched metastatic breast cancers.
Conclusions: The variations of these stromal reaction patterns from the primary to the metastasis shed lights on the relationship between the neoplastic cells and the non-neoplasic cells in the TME. The preservation of the CSF1 macrophage response pattern in metastases suggests a possible therapeutic target in these instances.
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 7, Wednesday Afternoon