New Biomarker Predicts Survival in Colorectal Cancer

October 5, 2006 - New Haven, Conn. — The location and amount of a protein within two separate compartments of a tumor cell may be critical markers predicting survival in colorectal cancer, according to a study at Yale School of Medicine.

The study revealed that high levels of the protein thymidylate synthase (TS) in the nucleus correlate with decreased patient survival time, and, further, a high ratio of TS in the nucleus relative to the level in the cytoplasm correlated with a shorter survival time.

“This is a new potential biomarker for predicting survival in patients with colorectal cancer,” said Mark Gustavson, lead author of the study and a postdoctoral fellow in the Department of Pathology.

He said this is the first study to show that the relationship between nuclear and cytoplasmic levels of TS can predict survival, although TS levels have been used as a marker for decreased survival and response to therapy.

The results were presented last month in Chicago at the first meeting on Molecular Diagnostics in Cancer Therapeutic Development, which was organized by the American Association for Cancer Research.

Gustavson and his colleagues determined subcellular TS levels using AQUA™, a system developed at Yale and licensed to HistoRx that combines fluorescence-based imaging, microscopy and high-throughput tissue microarray technologies, to determine subcellular TS levels.

Looking at 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. TS levels in the cytoplasm were also higher in patients with shorter survival times, though they were not as strong a predictor of survival as TS levels in the nucleus.

The researchers next looked at the ratio between TS levels in the nucleus and in the cytoplasm and discovered that a high ratio predicted decreased survival. Moreover, the cytoplasmic-to-nuclear ratio appeared to be an independent marker, not correlated with high nuclear levels. Among patients with a high ratio, more than half, 55 percent, did not have high nuclear levels.

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