P2-01-09: Gene Expression Alterations in the Lymph Node Microenvironment in Response to Successful Metastatic Colonization.

Abstract

Abstract Background: Breast stroma is known to play an active role in tumorigenesis, undergoing both phenotypic and molecular changes to facilitate and promote tumor development and growth. The metastatic microenvironment also plays a role in successful colonization; however, the genetic changes in these secondary microenvironments associated with metastasis are not well described. Methods: Women with invasive breast cancer with at least one lymph node with macrometastases and one lymph node with no detectable metastases were identified from the Clinical Breast Care Project. Lymph node tissue was microdissected from both the metastatic lymph node microenvironment and negative nodes and hybridized to U133A 2.0 gene expression arrays. Differential expression was detected using Partek® Genomics Suite™6.5 using a cutoff of P<0.001, >2-fold change. Results: Nineteen genes were differentially expressed between negative lymph nodes and lymph node tissue microdissected from lymph nodes with metastatic tumors. Eleven genes, including EPCAM, KRT19 and MUC1 were expressed at significantly higher levels in lymph node tissue from metastatic lymph nodes while eight genes, such as CXCL2 and CXCL5, were expressed at significantly higher levels in negative lymph nodes. Results have been validated in external sample sets for AZGP1, CLEC4M, CXCL2, EPCAM, MUC1, PIP and TFPI. Conclusions: Lymph node tissue differs in gene expression between those harboring metastatic tumors and those without metastasis. Genes expressed at higher levels in lymph nodes with macrometastases are involved in tumorigenesis, suggesting that like the breast stromal microenvironment, the metastatic microenvironment undergoes crosstalk with the tumor cells. In addition, a cluster of genes involved in immune function are expressed at lower levels in metastatic lymph nodes, suggesting that suppression of proper immune response may be required for successful metastatic colonization. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-01-09.