P-0064 ERCC1 Overexpression Predicts Poor Prognosis in Patients with Gastric/GE Junction Adenocarcinoma Treated with Adjuvant Cisplatin-Based Chemotherapy

Abstract

IntroductionAdjuvant chemotherapy is gaining an increasing role after curative resection for gastric cancer. Novel molecular markers could guide treatment decision-making, in order to better select candidates for adjuvant chemotherapy. The objective of our study was to analyze the status of excision repair cross-complementing gene 1 (ERCC1), thymidylate synthetase (TS) e p53, and correlate with outcome of patients who underwent adjuvant chemotherapy after curative resection for locally advanced gastric/GE junction adenocarcinoma. MethodsWe retrospectively evaluated patients with locally advanced gastric/GE junction adenocarcinoma (stage≥IB according to UICC classification), who underwent curative gastrectomy with D2 dissection, followed by adjuvant chemotherapy consisting of 4 to 6 courses of the ECF regimen (epirubicin 50 mg/m2 day 1, cisplatin 60 mg/m2 day 1, 5FU 200 mg/m2 protracted continuous infusion). Molecular analyses were performed on formalin-fixed paraffin-embedded tissues collected from surgical specimens. p53 mutations were analyzed by sequencing exons 4-10. Protein expression of ERCC1 and TS was assessed by immunohistochemistry (IHC), using specific monoclonal antibodies from Neomarkers. Real-time PCR (TaqMan assay) was performed to quantify mRNA ERCC1 expression. Statistical analyses were carried out using both Fisher'exact and Log Rank tests. ResultsSixty-eight patients were eligible for the study. There were 32 women (47%) and 36 men (53%). The median age was 69 (range: 30-74); UICC stage was III in 44 patients (65%). The median number of delivered chemotherapy cycles was 5.1 (range 4-6). With a median f-up was 40.5 months, disease-free and overall survival were 18.0 (95%CI: 13.4-22.76) and 56 months (95%CI: 44.87-67.13), respectively. We identified mutations in p53 in 21 out of 66 (32%) cases. ERCC1 expression was negative (score 0) in 14 out of 67 (21%) cases, whereas a positive score (score 1-3+) was observed in 53 (79%) cases. TS expression was negative (score 0) in 17 out of 67 (25%) cases, while a positive (score 1-3+) was found in 50 (75%) cases. High ERCC1 mRNA level was found in 19 out of 33 (57%) evaluable cases. Median overall survival was significantly longer in patients with ERCC1 negative tumors (p=0.04) by IHC, whilst TS, p53 and ERCC1 mRNA were not significantly associated with survival. ConclusionIn gastric/GE junction cancer patients after curative resection, ERCC1 by IHC might predict who is more likely to benefit from adjuvant platinum-based chemotherapy, according to the better overall survival observed in ERCC1 negative patients. In those exhibiting ERCC1 positive tumors, alternative chemotherapy regimens should be considered.