CSF-1 and Fibromatosis Expression in Stroma of Ductal Carcinoma In Situ
M Sharma, I Espinosa, AH Beck, JA Webster, KD Montgomery, M van de Rijn, KC Jensen, RB West. Stanford University, Palo Alto, CA; Palo Alto Veterans Affairs Health Care System, Palo Alto, CA
Background: Recent advances in the study of the tumor microenvironment (TME) have revealed the importance of the interaction between the tumor cells and their surrounding stroma in various malignancies. Our lab has previously shown that the CSF-1 and DTF signatures define two stromal reaction patterns seen in the microenvironment of invasive breast cancer (West Lab Invest, 2008; 88: 591). In this study we determine whether these signatures are also present in ductal carcinoma in situ (DCIS).
Design: Four markers for the CSF-1 response (CD163, FCGR3A, CTSL1, FCGR2B) and four markers for the DTF response (SPARC, MMP11, CDH11, SDC1) were examined using immunohistochemistry on tissue microarray (TMA) for 230 women with DCIS. The CSF-1 and DTF response was scored as 0 or 1 (no staining or <30% of cells showing strong staining) or 2 (>30% of cells showing strong staining). Scores were summed for all four markers within each signature. A sum of 3 or more was considered positive, and a sum of 2 or less was considered negative.
Results: 44% of all cases were positive for the CSF-1 signature and 40% were positive for the DTF signature. 24% of all cases showed a positive signature for both CSF-1 and DTF. In addition, there was increased expression of both the DTF and CSF-1 markers in High grade tumors when compared to Low grade tumors. There was a 1.8 X (p = 0.0002) increase in the percentage of cases positive for the DTF markers and a 2.8X (p < 0.0001) increase in the percentage of cases positive for the CSF-1 markers in High grade compared to Low grade tumors.
Conclusions: The CSF-1 and DTF gene signatures define stromal responses in DCIS. The level of stromal expression increases as grade increases. This study demonstrates that there are differential stromal reaction patterns in DCIS and that they may be similar to those seen in invasive carcinoma.
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 39, Tuesday Morning