Cancer Res Treat.  2005 Aug;37(4):216-222.

Thymidylate Synthase, Thymidine Phosphorylase, VEGF and p53 Protein Expression in Primary Colorectal Cancer for Predicting Response to 5-fluorouracil-based Chemotherapy

Affiliations
  • 1Department of Internal Medicine, College of Medicine, Hanyang University, Seoul, Korea. ahnmj@hanyang.ac.kr
  • 2Department of General Surgery, College of Medicine, Hanyang University, Seoul, Korea.
  • 3Department of Pathology, College of Medicine, Hanyang University, Seoul, Korea.

Abstract

PURPOSE
In the treatment of advanced metastatic colorectal cancer, several new agents, such as irinotecan and oxaliplatin, have been developed, which have improved both disease free and overall survivals. Among these agents, 5-fluorouracil (5-FU) still remains one of the most active agents, and the selection of patients who can benefit from 5-FU-based chemotherapy is still important, as those unlikely to benefit could be spared the harmful side effects. The expression levels of thymidylate synthase (TS), thymidine phosphorylase (TP) and p53 have been known to be associated with the clinical response to 5-FU-based therapy as well as the prognosis, and that of vascular endothelial growth factor (VEGF) is associated with poor survival. MATERIALS AND METHODS: The relationship between the expressions of TS, TP, VEGF and p53 in primary tumors, using immunohistochemistry, and the response of 45 metastatic colorectal cancer patients (M: F=25: 20, median age 59 yrs) to 5-FU-based chemotherapy were evaluated. RESULTS: Thirty-seven patients were treated with 5-FU/ LV/irinotecan (FOLFIRI) and 8 with 5-FU/LV/oxaplatin (FOLFOX). The overall response rate was 28.9% (13/45). When immunohistochemically analyzed with monoclonal antibodies against TS, TP, VEGF and p53, 55.6% of the patients (25/45) were positive for TS, 48.9% (22/45) for TP, 82.2% (37/45) for VEGF, and 80% (36/45) for p53. There was a significant difference in the intensity of TS expression between the clinical responders and non-responders (p=0.036). In terms of the staining pattern of TS expression, diffuse staining was correlated with a poor response (p=0.012) and poor survival (p=0.045). However, there was no correlation between the expressions of TP, VEGF or P53 and the response to chemotherapy. CONCLUSION: These results suggest that the expression of TS in primary colorectal cancer might be an important prognostic factor for chemotherapy response and survival, and might be a useful therapeutic marker for the response of chemotherapy.

Keyword

Thymidylate synthase; Thymidine phosphorylase; Vascular endothelial growth factor A; p53; Metastatic colorectal cancer; Fluorouracil

MeSH Terms

Antibodies, Monoclonal
Colorectal Neoplasms*
Drug Therapy*
Fluorouracil
Humans
Immunohistochemistry
Prognosis
Thymidine Phosphorylase*
Thymidine*
Thymidylate Synthase*
Vascular Endothelial Growth Factor A*
Antibodies, Monoclonal
Fluorouracil
Thymidine
Thymidine Phosphorylase
Thymidylate Synthase
Vascular Endothelial Growth Factor A
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