Fibroblast-Like Stromal Response Is Host-Dependent While Macrophage-Associated Stromal Response Is Tumor-Dependent: A Study of Stromal Response in Paired Breast Carcinomas from Patients with Dual Primaries
JM Wu, AH Beck, D Witten, K Allison, M van de Rijn, RB West. Stanford Unversity Medical Center, Palo Alto; University of Washington Medical Center, Seattle
Background: Recent work has demonstrated that stromal response genes correlate with tumor grade and patient survival. In breast cancer, the desmoid tumor fibromatosis (DTF)-like fibroblastic response is associated with lower grade and increased survival, whereas CSF1 macrophage response is associated with higher grade and decreased survival. It is unclear whether stromal response in these instances arises from a host response to the tumor, or whether the cancer induces a specific set of stromal responses. We explored this question by comparing stromal response signatures in patients with dual breast primaries.
Design: Seventeen patients with dual primaries were included in this study, with a total of 34 carcinoma cases analyzed. Immunohistochemical markers included previously defined DTF fibroblast expression signature genes (cadherin 11, MMP 11, CSPG2, CD138, osteonectin) and CSF1 macrophage response signature genes (cathepsin L, CD163, CD16, CD32). Analysis using paired mutation and Wilcoxon-Mann-Whitney test was performed to determine the relationship of stromal response arising from the patients' dual primaries.
Results: Permutation analysis demonstrated a significant, positive correlation for expression of DTF markers between the paired primary breast carcinomas (p=0.00268), whereas expression of CSF1 markers was not correlated between the 2 primaries (p=0.514). Of the individual markers, MMP11 (p=0.0052), cadherin 11 (p=0.0421), cathepsin L (p=0.00315) exhibited significant shared expression between the patients' 2 primaries. There was no correlation between histologic type (ductal vs lobular) and expression of DTF and CSF markers (p=0.975 and p=0.454). Similarly, there was no correlation with tumor location (p=0.100).
Conclusions: In studying the relationship between tumor and host response, we identified two sets of stromal signatures with divergent associations: one set of markers appears to be consistently expressed in a given patient regardless of tumor type (DTF fibroblast expression signature), while a second set of markers appears to be dependent on the inciting tumor (CSF1 macrophage expression signature). As the DTF fibroblast response has been associated with improved survival, this finding suggests that a subset of patients may generate a host response to tumors that favors good outcome.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 40, Monday Morning