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Novel biomarker for prediction of survival in colorectal carcinomas revealed

CHICAGO -- Levels of a protein called thymidylate synthase (TS) within two separate compartments of a tumor cell--the nucleus and the cytoplasm--may be critical markers predicting survival in colorectal cancer, according to a study at Yale University School of Medicine.

The study revealed two different and independent predictors of survival in colorectal cancer. One was TS levels in the nucleus--the higher the levels, the lower the survival time; and one was the ratio of TS levels in the nucleus to levels in the cytoplasm--the higher the ratio, the lower the survival time.

"TS levels have been known as a marker for decreased survival and response to therapy, but this is the first study to show that the relationship between nuclear and cytoplasmic levels of TS can predict survival," said first author Mark D. Gustavson, Ph.D., a postdoctoral fellow in Yale's Department of Pathology.

Results were presented at the first meeting on Molecular Diagnostics in Cancer Therapeutic Development, organized by the American Association for Cancer Research.

To determine subcellular TS levels, Gustavson and his colleagues used AQUATM, a system that combines fluorescence-based imaging with automated microscopy and high-throughput tissue microarray technologies. Developed at Yale and licensed to HistoRx, AQUA can measure protein concentrations within specific cells and cellular compartments in a highly reproducible and unbiased manner, Gustavson said.

Working with tissue samples from 518 colorectal cancer patients diagnosed between 1970 and 1981, the researchers found that just 51 percent of patients with high TS levels in the nucleus survived for five years compared to 71 percent of those with lower levels. The difference was highly statistically significant. TS levels in the cytoplasm were also higher in patients with lower survival times, though they were not as strong a predictor of survival as TS levels in the nucleus
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Contact: Warren Froelich
froelich@aacr.org
215-440-9300
American Association for Cancer Research
13-Sep-2006


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