Their study showed that levels of the protein called thymidylate synthase (TS) within two separate compartments of a tumor cell -- the nucleus and the cytoplasm -- may be markers for predicting survival among people with colorectal cancer.
For the study, the researchers measured TS levels in tissue samples from 518 colorectal cancer patients diagnosed between 1970 and 1981.
The researchers looked at the ratio between TS levels in the nucleus and in the cytoplasm and found that a low ratio predicted increased survival. Specifically, 65% of people with the lower ratio lived for five years or more vs. 45% of those with the higher ratio.
The ratio between cytoplasmic and nuclear TS appeared to be an independent predictor of survival regardless of TS nuclear levels, says researcher Mark D. Gustavson, PhD, a postdoctoral fellow in the department of pathology at Yale University.
"The ratio identifies a group of patients with worse prognosis that might otherwise be missed," he tells WebMD. "Doctors can then adjust therapy accordingly."
To determine subcellular TS levels, the researchers used a system -- developed at Yale and licensed to HistoRx -- that can measure protein concentrations within specific cells and cellular compartments in a highly reproducible manner.
Results were presented at the first meeting on Molecular Diagnostics in Cancer Therapeutic Development, organized by the American Association for Cancer Research.
Predicting Responses to Chemotherapy
Len Lichtenfeld, MD, deputy chief medical officer of the American Cancer Society, says that this is "clearly a new finding."
"The issue of measuring small amounts of protein in cells and using that information to predict survival is an area of great interest," he tells WebMD. "But there is still much work to be done to determine how to apply these findings to a large number of patients in the clinical setting."
The researchers are now performing a study to determine if TS levels can also help in predicting response to therapy with 5-FU, one of the standard chemotherapy drugs used in colorectal cancer.
"Very preliminary results suggest that the ratio is also predictive of how well patients will respond to 5-FU," Gustavson says.
SOURCES: Molecular Diagnostics in Cancer Therapeutic Development Meeting, Chicago, Sept. 12-15, 2006. Mark D. Gustavson, PhD, postdoctoral fellow, department of pathology, Yale University. Len Lichtenfeld, MD, deputy chief medical officer, American Cancer Society.
By Charlene Laino
Reviewed by Louise Chang