Protein Gene Expression Predicts Breast Cancer Prognosis

High levels of inducible nitric oxide synthase (NOS2) are a predictor for survival in estrogen receptor (ER) negative breast cancer.

Inducible NOS2 is an inflammation-responsive enzyme that is unregulated in acute and chronic inflammation as part of host defense and the wound-healing process. Upregulation of this enzyme leads to increased nitric oxide (NO) production, by which it affects the redox state of cells.

In a study carried out at the U.S. National Cancer Institute, (Bethesda, MD, USA), scientists examined NOS2 expression and its association with tumor markers and survival in 248 breast tumors. Fresh frozen and paraffin-embedded tissue tumor specimens were tested using immunohistochemistry techniques with monoclonal antibodies. Enriched tumor epithelium from 32 fresh-frozen surgical breast tumors was obtained by laser capture microdissection (LCM), of those, 17 had low NOS2 expression, and 15 had high NOS2 expression. Other tests, such as Western Blots analysis, gene expression analysis and, an enzyme-linked immunoassay (ELISA) for interleukin 8 (IL-8) were performed.

High NOS2 expression was significantly associated with decreased survival of these patients with ER-negative breast cancer, but not of ER-positive breast cancer patients. This finding was further corroborated by a test for interaction showing that the tumor ER status modifies the effect of NOS2 on breast cancer survival. However, even among ER-negative breast tumors, those characterized as basal-like are the most aggressive and difficult to treat.

Stefan Ambs, Ph.D., the senior investigator, suggested that the protein NOS2 could be a good drug target and that selective NOS2 inhibitors might be of benefit to these individuals with ER-negative breast cancer. The study was published on October 18, 2010, in the Journal of Clinical Investigation.

Related Links:
U.S. National Cancer Institute