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Thymidylate Synthase
spacer Thymidylate synthase (TS) is the limiting irreversible step in de novo DNA, catalyzing the conversion of dUMP to dTMP. It is the target for the widely used anticancer agent 5-fluorouracil (5-FU), which is active against solid tumors like breast, head and neck and colon cancers. Increased TS levels in tumors are associated with resistance to chemotherapy with 5-FU. In addition, TS expression has been shown to be an independent prognostic factor in several cancers.

For example, intratumoral TS expression has a significantly adverse influence on loco-regional recurrence, distant metastasis, overall survival, and disease free survival in colorectal cancer patients. Comparable results have been found in other tumor types such as gastric, ovarian, cervical and head and neck cancers, with TS+ tumors having significantly worse outcome compared to TS- cases.

TS levels in tumors can be measured either enzymatically or using TS mRNA levels, but both methodologies require fresh or frozen tissues, and do not discriminate between "normal" and "neoplastic" complements of the enzyme. In contrast, immunohistochemistry permits identification of TS specific to the neoplastic cells, and is applicable to routine formalin-fixed archival tissues.

The combined evaluation of COX-2/TS in Colorectal Cancers can determine therapeutic strategy in these patients and the test has been deemed especially useful in diffuse peritoneal mucinomatosis.

Veripath OncoDiagnostics has optimized the use of the monoclonal TS-106 TS antibody, which has been extensively used in previous studies. Currently, we are using an automated image analysis system to quantitatively score percentage positivity and intensity grade for TS finally reflected in a histoscore on each evaluation. TS comes as part of the standard colorectal, esophagus, and stomach cancer panels, but can also be ordered individually. For more information contact Dr Raheela Ashfaq at Veripath OncoDiagnostics at 214.645.7053 or
.

Selected references:

1. Edler D et al. Thymidylate synthase expression: an independent prognostic factor for local recurrence, distant metastasis, disease-free and overall survival in rectal cancer. Clin Cancer Res 6:1378; 2000

2. Suda Y et al. Immunohistochemical detection of thymidylate synthase in advanced gastric cancer: a prognostic indicator in patients undergoing gastrectomy followed by adjuvant therapy with 5-fluoropyrimidines. Anticancer Res 19:805; 1999

3. Suzuki M et al. Enhanced expression of thymidylate synthase may be of prognostic importance in advanced cervical cancer. Oncology 57:50; 1999

4. Yamachika T et al. A new prognostic factor for colorectal carcinoma, thymidylate synthase, and its therapeutic significance. Cancer 82:70; 1998

 
Markers Available

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