Inducible nitric oxide synthase (NOS2) is involved in wound healing

BackgroundAfrican-American breast cancer patients experience higher mortality rates than European-American patients despite having a lower incidence of the disease. We tested the hypothesis that intrinsic differences in the tumor biology may contribute to this cancer health disparity.Methods and ResultsUsing laser capture microdissection, we examined genome-wide mRNA expression specific to tumor epithelium and tumor stroma in 18 African-American and 17 European-American patients. Numerous genes were differentially expressed between these two patient groups and a two-gene signature in the tumor epithelium distinguished between them. To identify the biological processes in tumors that are different by race/ethnicity, Gene Ontology and disease association analyses were performed. Several biological processes were identified which may contribute to enhanced disease aggressiveness in African-American patients, including angiogenesis and chemotaxis. African-American tumors also contained a prominent interferon signature. The role of angiogenesis in the tumor biology of African-Americans was further investigated by examining the extent of vascularization and macrophage infiltration in an expanded set of 248 breast tumors. Immunohistochemistry revealed that microvessel density and macrophage infiltration is higher in tumors of African-Americans than in tumors of European-Americans. Lastly, using an in silico approach, we explored the potential of tailored treatment options for African-American patients based on their gene expression profile. This exploratory approach generated lists of therapeutics that may have specific antagonistic activity against tumors of African-American patients, e.g., sirolimus, resveratrol, and chlorpromazine in estrogen receptor-negative tumors.ConclusionsThe gene expression profiles of breast tumors indicate that differences in tumor biology may exist between African-American and European-American patients beyond the knowledge of current markers. Notably, pathways related to tumor angiogenesis and chemotaxis could be functionally different in these two patient groups.

The factors that determine whether a breast carcinoma will develop into inflammatory breast cancer (IBC) remain poorly understood. Recent evidence indicates that the tumor stroma influences cancer phenotypes. We tested the hypotheses that the gene expression signature of the tumor stroma is a distinctive feature of IBC. We used laser capture microdissection to obtain enriched populations of tumor epithelial cells and adjacent stromal cells from 15 patients with IBC and 35 patients with invasive, noninflammatory breast cancer (non-IBC). Their mRNA expression profiles were assessed using Affymetrix GeneChips TM . In addition, a previously established classifier for IBC was evaluated for the resulting data sets. The gene expression profile of the tumor stroma distinguished IBC from non-IBC, and a previously established IBC prediction signature performed better in classifying IBC using the gene expression profile of the tumor stroma than it did using the profile of the tumor epithelium. In a pathway analysis, the genes differentially expressed between IBC and non-IBC tumors clustered in distinct pathways. We identified multiple pathways related to the endoplasmic stress response that could be functionally significant in IBC. Our findings suggest that the gene expression in the tumor stroma may play a role in determining the IBC phenotype. ' 2007 Wiley-Liss, Inc.

A strong interaction between SNP309 status and tumor p53 status appears to modify the association between p53 status and breast cancer survival.