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Among patients with Duke’s C colorectal cancer, low levels of the enzyme thymidylate synthase in lymph node metastases are associated with better survival, according to a study published in the Journal of Clinical Oncology.

Colorectal cancer is the second leading cause of cancer-related deaths in the United States. Dukes’ C (stage III) colorectal cancer refers to cancer that has spread from the colon to nearby lymph nodes, but not to distant sites in the body. Patients with Dukes’ C colon cancer are generally treated with surgery to remove the cancer and later with adjuvant chemotherapy (secondary treatment given to increase the effectiveness of the primary treatment). A chemotherapy regimen typically consists of the agent 5-fluorouracil (5-FU) alone or in combination with other agents.

Thymidylate synthase (TS) is an enzyme that is the target of several chemotherapy drugs. Inhibition of TS by drugs such as 5-flourouracil results in cancer cell death. In colorectal cancer, level of TS in the primary cancer (the cancer in the colon or rectum) has earned research attention because it may predict survival or response to chemotherapy drugs. There is also interest in level of TS in cancer that has spread outside of the colon or rectum. Level of TS in lymph node metastases, for example, may differ from level in the primary cancer and may have an independent effect on survival.

To evaluate the relationship between level of TS in lymph node metastases and survival of colorectal cancer patients, researchers in Sweden evaluated 348 patients with Dukes’ C colorectal cancer. This clinical trial compared treatment with surgery alone to surgery plus chemotherapy. In the overall patient group, patients with low TS levels in lymph node metastases had better survival than patients with higher levels. When researchers analyzed the two treatment groups separately, they found that low TS levels predicted improved survival in the group treated with surgery alone, but not in the group treated with surgery and chemotherapy. The researchers speculate that fluorouracil-based chemotherapy may reduce the survival difference between patients with high and low TS levels. For 28% of patients, TS levels in lymph node metastases were different than TS levels in the primary cancer. Among patients with low TS level in the primary cancer, TS level of the lymph node metastases was an important independent predictor of survival.

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The researchers conclude that TS levels in lymph node metastases of colorectal cancer patients predict survival. Patients with lower TS levels had longer survival. The researchers recommend additional studies to confirm the role of TS in colorectal cancer survival and response to chemotherapy.

Reference: Öhrling K, Edler D, Hallström M et al. Detection of thymidylate synthase expression in lymph node metastases of colorectal cancer can improve the prognostic information. *Journal of Clinical Oncology.*2005;23:5628-34

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