Metastatic Tumors

A study comparing the gene expression profile of localized and metastatic prostate cancer demonstrated the power of microarrays in the development of predictive markers.22 Varambally and colleagues23 found overexpression of the polycomb group protein enhancer of zeste homolog 2 (EZH2) in hormone-refractory metastatic prostate cancer. The overexpression of EZH2 was validated using tissue arrays to show that the protein is overexpressed in the metastatic tumors, and application of an emerging powerful technology called RNA interference to disrupt expression of EZH2 resulted in growth inhibition of a cell line derived from human metastatic prostate cancer.

Two microarray studies have challenged the hypothesis that tumors develop a metastatic potential as they grow. The studies tested the hypothesis that primary tumors harbor the necessary information to determine which tumors are more likely to metastasize. By comparing a series of breast tumors from node-negative and node-positive patients, van de Vijver et al.19 found an expression profile that correlated with a poor prognosis and higher risk of metastasis. A second study suggests a broader applicability of these findings. Ramaswamy et al. discovered a genetic signature predictive of outcome by analyzing a variety of primary and metastatic adenocarcinomas.24 A set of 17 differentially expressed genes present in the metastases was found in certain primary tumors without known metastases, and was associated with a poor prognosis.

By using these specific gene expression signatures, the metastatic potential of even early tumors could be established, thereby identifying patients that should be treated more aggressively.

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