Cancer Res Treat.  2014 Jan;46(1):55-64.

Combination of TRAP1 and ERCC1 Expression Predicts Clinical Outcomes in Metastatic Colorectal Cancer Treated with Oxaliplatin/5-Fluorouracil

• Han JJ
• Baek SK
• Lee JJ
• Kim GY
• Kim SY
• Lee SH

Abstract

PURPOSE
The novel heat shock protein tumor necrosis factor receptor-associated protein 1 (TRAP1) is associated with multidrug resistance in colorectal cancer (CRC) cells in vitro. Excision repair cross-complementation group 1 (ERCC1) expression levels in tumor tissues also predict clinical outcomes in metastatic CRC patients receiving combination oxaliplatin and 5-fluorouracil treatment. We investigated whether TRAP1 and ERCC1 protein expression by immunohistochemistry predict clinical outcomes in CRC patients.
MATERIALS AND METHODS
The study population consisted of 56 patients with metastatic CRC who received first-line oxaliplatin/5-fluorouracil therapy. Clinical response and overall survival (OS) by levels of the markers TRAP1 and ERCC1 were evaluated.
RESULTS
The rates of TRAP1 and ERCC1 expression were 21% and 52%, respectively. Patients negative for ERCC1 expression showed a tendency to respond to chemotherapy (p=0.066). Median OS was significantly longer in patients negative for TRAP1 than those positive for TRAP1 (p=0.023). Patients negative for ERCC1 expression also had a better OS than those positive for ERCC1 (p=0.021). The median OS was 30.9 months for patients negative for TRAP1 and ERCC1 compared to 13.2 months for those positive for TRAP1 and/or positive for ERCC1 expression (p=0.006). The combination of TRAP1 and ERCC1 expression was significantly associated with the response to chemotherapy (p=0.046) and independently predicted median OS in multivariate analysis (hazard ratio, 2.98; 95% confidence interval, 1.18 to 7.49).
CONCLUSION
The present study demonstrates that the combination of TRAP1 and ERCC1 expression predicts the survival of metastatic CRC patients who were treated with oxaliplatin/5-fluorouracil.

Keyword

Colorectal neoplasms; ERCC1; Fluorouracil; Oxaliplatin; TRAP1

MeSH Terms

Colorectal Neoplasms*
DNA Repair
Drug Resistance, Multiple
Drug Therapy
Fluorouracil
Heat-Shock Proteins
Humans
Immunohistochemistry
Multivariate Analysis
Tumor Necrosis Factor-alpha
Fluorouracil
Heat-Shock Proteins
Tumor Necrosis Factor-alpha

Figure

• 

  Fig. 1 Immunohistochemical staining of a tumor necrosis factor receptor-associated protein 1 (TRAP1) (A, D), excision repair cross-complementing 1 (ERCC1) (B, E), and thymidylate synthase (TS) (C, F) on paraffin sections of colorectal carcinoma specimens (A-F; ×400).

• 

  Fig. 2 Overall survival (OS) curve for 56 patients according to tumor necrosis factor receptor-associated protein 1 (TRAP1) (A), excision repair cross-complementing 1 (ERCC1) (B), and thymidylate synthase (TS) (C) expression.

• 

  Fig. 3 Overall survival (OS) curve for 56 patients according to tumor necrosis factor receptor-associated protein 1 (TRAP1)/excision repair cross-complementing 1 (ERCC1) score (score 0, negative TRAP1 and negative ERCC1; score 1, either positive TRAP1 or positive ERCC1; score 2, positive TRAP1 and positive ERCC1).

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