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Stromal gene expression predicts clinical outcome in breast cancer.

Stromal gene expression predicts clinical outcome in breast cancer

Finak G, Bertos N, Pepin F et al.

Nature Medicine, 2008, 14, 518-527

The biological role of tumour-associated stroma is not well understood and often overlooked. Gene expression profiling of epithelial breast cancer cells has seen much activity in recent years and has led to a better understanding of breast cancer cell behaviour and the now well-known subclassification of human breast cancer. By contrast, the contribution and influence of the tumour stroma has not been studied in great detail despite evidence that mechanisms of angiogenesis, metastasis and invasion are closely linked to stromal-tumour interactions.

The present thought-provoking study redresses this balance and provides new possible prognostic and therapeutic information. Using laser capture microdissection of stroma from both normal and tumour-derived tissue, the authors have identified initially a 163-gene set that can predict for good or poor outcome within 53 primary breast cancers. The genes involved range from hypoxic and angiogenic factors to those with tumour-associated macrophage functions, and are biologically relevant as they are known to be associated with outcome.

Furthermore, the authors have derived a smaller set of 26 genes, which they call the stroma-derived prognostic predictor (SDPP) and which is able to stratify tumours into poor and good prognostic groups, and appears to outperform the classic tumour cell-derived gene signatures. Among the 26 genes are several involved in regulation of natural killer cell function, T-cell activation, cell adhesion and matrix formation, bone and calcium metabolism and regulation of epithelial cell proliferation. Of particular interest is the identification of osteopontin (SPPI) as upregulated in poor outcome stroma, as we are in an era of large randomised clinical trials using potent bisphosphonate and anti-angiogenic drugs for breast cancer patients in the adjuvant setting. It is conceivable that our therapies in the future will more and more be targeted at the stroma as well as the tumour within.

Commentary by Peter Barrett-Lee

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Article Details
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Author:Barrett-Lee, Peter
Publication:Advances in Breast Cancer
Article Type:Report
Geographic Code:4EUUK
Date:Jun 1, 2008
Words:320
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