Molecular Diagnostics

British Journal of Cancer (2008) 98, 832–839. doi:10.1038/sj.bjc.6604211 www.bjcancer.com
Published online 29 January 2008

Impacts of excision repair cross-complementing gene 1 (ERCC1), dihydropyrimidine dehydrogenase, and epidermal growth factor receptor on the outcomes of patients with advanced gastric cancer

J Matsubara1, T Nishina2, Y Yamada1, T Moriwaki2, T Shimoda3, T Kajiwara2, T E Nakajima1, K Kato1, T Hamaguchi1, Y Shimada1, Y Okayama4, T Oka4 and K Shirao1

  1. 1Gastrointestinal Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji Chuo-ku, Tokyo 1040045, Japan
  2. 2Department of Gastroenterology, National Hospital Organization Shikoku Cancer Center, 160 Kou Minamiumemoto-cho, Matsuyama 7910280, Japan
  3. 3Clinical Laboratory Division, National Cancer Center Hospital, 5-1-1 Tsukiji Chuo-ku, Tokyo 1040045, Japan
  4. 4Personalized Medicine Research Laboratory, Taiho Pharmaceutical Co. Ltd, 224-2 Hiraishiebisuno Kawauchi-cho, Tokushima 7710194, Japan

Correspondence: Dr Y Yamada, E-mail: yayamada@ncc.go.jp

Received 8 October 2007; Revised 3 January 2008; Accepted 3 January 2008; Published online 29 January 2008.

Top

Abstract

Using laser-captured microdissection and a real-time RT–PCR assay, we quantitatively evaluated mRNA levels of the following biomarkers in paraffin-embedded gastric cancer (GC) specimens obtained by surgical resection or biopsy: excision repair cross-complementing gene 1 (ERCC1), dihydropyrimidine dehydrogenase (DPD), methylenetetrahydrofolate reductase (MTHFR), epidermal growth factor receptor (EGFR), and five other biomarkers related to anticancer drug sensitivity. The study group comprised 140 patients who received first-line chemotherapy for advanced GC. All cancer specimens were obtained before chemotherapy. In patients who received first-line S-1 monotherapy (69 patients), low MTHFR expression correlated with a higher response rate (low: 44.9% vs high: 6.3%; P=0.006). In patients given first-line cisplatin-based regimens (combined with S-1 or irinotecan) (43 patients), low ERCC1 correlated with a higher response rate (low: 55.6% vs high: 18.8%; P=0.008). Multivariate survival analysis of all patients demonstrated that high ERCC1 (hazard ratio (HR): 2.38 (95% CI: 1.55–3.67)), high DPD (HR: 2.04 (1.37–3.02)), low EGFR (HR: 0.34 (0.20–0.56)), and an elevated serum alkaline phosphatase level (HR: 1.00 (1.001–1.002)) were significant predictors of poor survival. Our results suggest that these biomarkers are useful predictors of clinical outcomes in patients with advanced GC.

Keywords:

gastric cancer, excision repair cross-complementing gene 1, dihydropyrimidine dehydrogenase, epidermal growth factor receptor, prognostic factor