Differential gene and protein expression in primary breast malignancies and their lymph node metastases as revealed by combined cDNA microarray and tissue microarray analysis.

摘要: BACKGROUND Metastatic disease is a major adverse prognostic factor in breast carcinoma. Lymph node metastases often represent the first step metastatic process. METHODS To gain insight into molecular events that underlie carcinoma metastasis, authors compared gene expression profiles, obtained by cDNA microarray analysis, of nine matched primary tumors and after screening for enrichment tumor cells. Statistical analysis identified genes are expressed at elevated or decreased levels relative to corresponding tumors. Multidimensional scaling indicated terms levels, were tightly clustered, whereas exhibited greater spread; this finding points more heterogeneous nature metastases. Among differentially entities invasion- tissue modeling–related IGFBP5, fibronectin, MMP2; cell cycle regulatory cyclin D1; other genes, such as enolase 2; an sequence tag similar angiopoietin 1. To validate extend these initial findings, constructed consisting 100 malignancies paired with their lymph Antibodies IGFBP-5, MMP-2, D1, MDM-2 proteins used stain array sections. RESULTS Consistent data, statistically significant overexpression down-regulation unchanged observed Nonetheless, although fibronectin MMP2 mRNA many metastasis specimens, extracellular matrix most Decreased was further confirmed real-time polymerase chain reaction assays performed on five additional specimen pairs. CONCLUSIONS The results current study suggest protein nuclear associated via negative-feedback mechanism. Therefore, profiling validation should be combined elucidate process. Cancer 2004. © 2004 American Society.