Excision repair cross‐complementing gene‐1, ribonucleotide reductase subunit M1, ribonucleotide reductase subunit M2, and human equilibrative nucleoside transporter‐1 expression and prognostic value in biliary tract malignancy

Abstract

BACKGROUND: Tumor expression of excision cross-complementing gene-1 (ERCC1), human equilibrative nucleoside transporter 1 (hENT1), ribonucleotide reductase subunit M1 (RRM1), and ribonucleotide reductase subunit M2 (RRM2), is associated with the efficacy of platinum and gemcitabine chemotherapy. The authors of this report recently demonstrated that high ERCC1 and RRM2 expression levels are independent negative prognostic markers for survival in early stage pancreas cancer. The differential expression and prognostic value of these biomarkers in biliary tract malignancy (BTM) is unknown. METHODS: In total, 63 patients who had tissue available for analysis were selected from a prospective database of all patients (n ¼ 104) who underwent resection of BTM (intrahepatic, hilar, or distal cholangiocarcinoma; gallbladder carcinoma) between January 2000 and December 2008. Immunohistochemistry for ERCC1, hENT1, RRM1, and RRM2 expression was performed. Staining was scored by a single pathologist who was blinded to patient outcomes. RESULTS: The median patient age was 67 years. The median overall survival (OS) was 16.2 months, and the median follow-up was 32.7 months. Only 3 BTMs (4.8%) had high ERCC1 expression, and 92.1% and 81% of BTMs exhibited high hENT1 and RRM1 expression, respectively. RRM2 expression varied, and 32% of tumors demonstrated high RRM2 expression. ERCC1 and RRM1 were not associated with OS. High RRM2 expression was associated with a trend toward improved OS (30.8 months vs 16.2 months; P ¼ .06), and high hENT1 expression was associated with improved OS (17.7 months vs 9.5 months; P ¼ .04). CONCLUSIONS: Most BTMs exhibited low ERCC1 expression and high hENT1 and RRM1 expression, whereas RRM2 expression levels varied. High expression of hENT1 was associated with improved OS. These findings may have implications for the selection of chemotherapy agents (gemcitabine vs platinum) and the stratification of patients in chemotherapy trials that assess outcome. Cancer 2013;119:454-62.

Impact of a Biomarker-Based Strategy on Oncology Drug Development: A Meta-analysis of Clinical Trials Leading to FDA Approval

“…All personalized drugs were classified as targeted agents, and no cytotoxic agents were considered personalized. This finding may reflect the fact that the precise mechanism of action of cytotoxic agents and the biomarkers for them have only recently been explored (28,29). The hazard ratio for overall survival in the randomized trials was better with personalized treatment, although this did not reach statistical significance in multivariate analysis (P = 0.07).…”

“…29). Agents that were tested with a personalized strategy were all considered to be targeted agents (Table 1).…”

Epidermal growth factor receptor overexpression is a marker for adverse pathologic features in papillary thyroid carcinoma

“…All pathologists were blinded to clinicopathologic variables and outcomes while assessing IHC results. The scoring system was modeled after one previously used at our institution designed to account for both staining intensity and percentage of cells staining (25, 26). No EGFR expression was defined as 0+ staining intensity in all tumor cells.…”

Predictive and prognostic values of ERCC1 and XRCC1 in biliary tract cancers

“…In BTCs, very little data exists on ERCC1. One study has suggested that low expression is a good overall prognostic indicator for PHCC and CBDAC,7 while another study suggested no predictive value 8. Recently, it was shown that ERCC1 was unable to predict response in patients undergoing platinum-based palliative chemotherapy 9.…”