Recently, Dr. Condeelis found that breast cancer spreads only when a specific trio of cells are present together in the same microanatomic site: an endothelial cell (a type of cell that lines the blood vessels), a perivascular macrophage (a type of immune cell found near blood vessels), and a tumor cell that produces Mena. The protein Mena was shown to enhance a cancer cell’s invasiveness in a collaborative study from Dr. Condeelis and Frank Gertler at the Koch Institute for Integrative Cancer Research at MIT published in Developmental Cell in December. A site with these three cells constitutes what is called a tumor microenvironment of metastasis, or TMEM.

The NewYork-Presbyterian/Weill Cornell investigators, aided by the Einstein and MIT scientists, then developed a tissue test to detect the presence and density of TMEMs. The test consists of a triple immunostain containing antibodies to the three cell types. A high number of TMEMs in a tissue sample means that the tumor is likely to metastasize or has already done so. In the current study, the immunostain was tested on breast tissue biopsy samples taken from 30 patients with advanced metastatic breast cancer and 30 patients with localized breast cancer, all of whom had been followed for at least five years. The resulting immunostains were evaluated by two pathologists who were not aware of the patients’ clinical outcomes.

Their analysis confirmed that TMEM density was significantly higher in patients who had developed metastatic breast cancer than in those who had localized disease. For every ten-unit increase in TMEM density, the risk for metastatic disease doubled. The density of any of three TMEM components alone was not sufficient to predict clinical outcome.

The study also showed that the ability of the TMEM density test to predict metastatic disease was independent of other currently used predictors, including lymph node metastasis, tumor size, presence of lymphovascular invasion, and tumor grade.

While the new test promises to reduce overtreatment of breast cancer, it could reduce undertreatment as well. “There are some patients with Grade 1 breast cancer who ultimately develop metastatic disease,” says Dr. Condeelis. “By measuring TMEM counts, we could identify those people and treat them appropriately.

”The researchers are currently working on a blood test for predicting metastatic breast cancer. In theory, such a test could predict the risk of metastatic disease even before a tumor forms. “It could be part of a routine checkup, especially for women with a strong family history of the disease,” says Dr. Condeelis. Before such a blood test could be developed for commercial use, researchers will need to conduct a population study. The paper, “TMEM in Human Breast Carcinoma: A Potential Prognostic Marker Linked to Hematogenous Dissemination,” was published March 24th, 2009 in the online version of Clinical Cancer Research.

In addition to Dr. Condeelis, the co-authors of the paper include: Brian D. Robinson, Gabriel L. Sica, Yi-Fang Liu, Joan G. Jones of NewYork-Presbyterian Hospital/Weill Cornell Medical Center; Frank B. Gertler of Massachusetts Institute of Technology; and Thomas E. Rohan, professor of epidemiology and population health at Einstein.

Source-Eurekalert
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