Predictive value of ERCC1, ERCC2, and XRCC1 overexpression for stage III colorectal cancer patients receiving FOLFOX-4 adjuvant chemotherapy.

Abstract

OBJECTIVES:

To determine the correlation between expression of three DNA repair genes and early failure/clinical outcome of stage III colorectal cancer (CRC) patients administrated with FOLFOX-4, including the excision repair cross-complementation group 1 (ERCC1), the excision repair cross-complementing 2 (ERCC2), and X-ray repair cross-complementing protein 1 (XRCC1).

MATERIALS AND METHODS:

We retrospectively analyzed clinicopathological features and ERCC1, ERCC2, XRCC1 expressions by immunohistochemical staining in 180 stage III CRC patients undergoing curative resection and treated with FOLFOX-4 chemotherapy to identify predictors of postoperative early failure.

RESULTS:

Among 180 CRC patients, 44 patients were classified into early failure group, and 136 patients were categorized into non-early failure group. A multivariate logistic regression analysis showed that ERCC1 overexpression (P = 0.005), and high postoperative carcinoembryonic antigen (CEA) levels (P = 0.001) were independent predictors of early failure. Additionally, ERCC1 overexpression was not only a predictor of early failure but also for disease-free survival (P < 0.001) and overall survival (P < 0.001). However, no predictive roles of ERCC2 and XRCC1 expression among these analyzed patients.

CONCLUSIONS:

ERCC1 overexpression is an important predictor of early failure in patients with stage III CRC administrating FOLFOX-4 adjuvant chemotherapy and this marker may help identify patients who would benefit from intensive follow-up and enhance therapeutic programs.

• Authors: Ming-Yii Huang, Hsiang-Lin Tsai, Chih-Hung Lin, Ching-Wen Huang, Cheng-Jen Ma, Chun-Ming Huang, Chee-Yin Chai, Jaw-Yuan Wang
• Journal: Journal of surgical oncology (J Surg Oncol) Vol. 108 Issue 7 Pg. 457-64 (Dec 2013) ISSN: 1096-9098 [Electronic] United States
• PMID: 23996617 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 Wiley Periodicals, Inc.

Chemical References

• DNA-Binding Proteins
• Organoplatinum Compounds
• X-ray Repair Cross Complementing Protein 1
• XRCC1 protein, human
• ERCC1 protein, human
• Endonucleases
• Xeroderma Pigmentosum Group D Protein
• ERCC2 protein, human
• Leucovorin
• Fluorouracil

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Chemotherapy, Adjuvant
• Colorectal Neoplasms (genetics, metabolism, pathology, therapy)
• DNA Repair
• DNA-Binding Proteins (biosynthesis, genetics)
• Disease-Free Survival
• Endonucleases (biosynthesis, genetics)
• Female
• Fluorouracil (administration & dosage)
• Gene Expression
• Humans
• Immunohistochemistry
• Leucovorin (administration & dosage)
• Male
• Middle Aged
• Neoplasm Staging
• Organoplatinum Compounds (administration & dosage)
• Retrospective Studies
• Treatment Outcome
• X-ray Repair Cross Complementing Protein 1
• Xeroderma Pigmentosum Group D Protein (biosynthesis, genetics)