Prognostic value of ERCC1, thymidylate synthase, and glutathione S-transferase pi for 5-FU/oxaliplatin chemotherapy in advanced colorectal cancer.

Abstract

BACKGROUND:

The aim of this study was to determine whether the expression of the excision repair cross-complementing 1 (ERCC1), thymidylate synthase (TS) and glutathione S-transferase pi (GSTpi) predict clinical outcome in patients with advanced colorectal cancer treated with fluorouracil (5-FU)/oxaliplatin chemotherapy.

METHODS:

The study population consisted of 70 patients with advanced colorectal cancer (median age, 54 years). Patients were treated with oxaliplatin 85 mg/m as a 2-hour infusion on days 1 plus leucovorin (LV) 20 mg/m over 10 minutes, followed by 5-FU bolus 400 mg/m and a 22-hour continuous infusion of 600 mg/m from day 1 to 2. Treatment was repeated at 2-week intervals. The expression of ERCC1, TS, and GSTpi in primary tumors was examined using immunohistochemistry.

RESULTS:

ERCC1, TS, and GSTpi were positive in 55.7%, 68.6%, and 71.4% of cases, respectively. Patients without TS expression were more likely to respond to chemotherapy (P = 0.009). There were no significant differences between response to treatment and the ERCC1 or GSTpi expression pattern (P = 0.768, P = 0.589, respectively). The median overall survival (OS) was significantly longer in patients without ERCC1 expression (P = 0.0474). Patients who were ERCC1 positive combined with TS positive, or those with ERCC1 positive combined with TS positive and GSTpi positive had a poor OS (P = 0.0017, P = 0.0323, respectively). Multivariate analysis revealed that both ERCC1 and TS expression significantly impacted OS (hazard ratio 1.72, P = 0.023).

CONCLUSION:

Immunohistochemical study of ERCC1 and TS may be useful for the prediction of clinical outcome in patients with advanced colorectal cancer treated with 5-FU and oxaliplatin.

• Authors: Sung-Hyun Kim, Hyuk-Chan Kwon, Sung Yong Oh, Dong Mee Lee, Suee Lee, Jong-Hoon Lee, Mee-Sook Roh, Dae-Cheol Kim, Ki-Jae Park, Hong-Jo Choi, Hyo-Jin Kim
• Journal: American journal of clinical oncology (Am J Clin Oncol) Vol. 32 Issue 1 Pg. 38-43 (Feb 2009) ISSN: 1537-453X [Electronic] United States
• PMID: 19194123 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• DNA-Binding Proteins
• Organoplatinum Compounds
• Oxaliplatin
• Thymidylate Synthase
• GSTP1 protein, human
• Glutathione S-Transferase pi
• ERCC1 protein, human
• Endonucleases
• Fluorouracil

Topics

• Adenocarcinoma (drug therapy, enzymology, secondary)
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers, Tumor (metabolism)
• Colorectal Neoplasms (drug therapy, enzymology, pathology)
• DNA Repair
• DNA-Binding Proteins (metabolism)
• Endonucleases (metabolism)
• Female
• Fluorouracil (administration & dosage)
• Follow-Up Studies
• Glutathione S-Transferase pi (metabolism)
• Humans
• Immunoenzyme Techniques
• Liver Neoplasms (drug therapy, enzymology, secondary)
• Lung Neoplasms (drug therapy, enzymology, secondary)
• Lymphatic Metastasis
• Male
• Middle Aged
• Organoplatinum Compounds (administration & dosage)
• Oxaliplatin
• Peritoneal Neoplasms (drug therapy, enzymology, secondary)
• Prognosis
• Retrospective Studies
• Survival Rate
• Thymidylate Synthase (metabolism)
• Treatment Outcome