caa a22 4500 445333839 CHVBK 20180317142746.0 cr unu---uuuuu 170323e20110901xx s 000 0 eng 10.1245/s10434-011-1610-x doi (NATIONALLICENCE)springer-10.1245/s10434-011-1610-x Differential Expression of ERCC1 in Pancreas Adenocarcinoma: High Tumor Expression is Associated with Earlier Recurrence and Shortened Survival after Resection [Elektronische Daten] [Shishir Maithel, Ipek Coban, Peter Kneuertz, David Kooby, Bassel El-Rayes, John Kauh, Juan Sarmiento, Charles Staley III, N. Volkan Adsay] Background: Increased tumor expression of excision repair cross-complementing gene-1 (ERCC1) is associated with decreased survival in patients with various cancers. Its effect in pancreatic adenocarcinoma (PAC) is not defined. Methods: Ninety-five patients were selected from a prospective database of all patients (n=220) who underwent pancreaticoduodenectomy for PAC between January 2000 and October 2008. Tumor was isolated to perform immunohistochemistry for ERCC1 expression and was graded by a single pathologist. Main outcomes were recurrence-free survival (RFS) and overall survival (OS). Results: Median age was 63years; 50 patients (53%) were male and 73 (77%) received adjuvant chemotherapy. Median follow-up was 25months. Median RFS and OS was 9 and 16months. Median tumor size was 3cm; 26% had a positive resection margin, 34% had poorly differentiated tumors, 61% had positive lymph nodes, 88% had perineural invasion, and 45% had lymphovascular invasion. Tumors exhibited differential ERCC1 expression in terms of intensity staining [none-weak: 61%; moderate-strong: 39%], percentage staining [0: 39%; 1-10: 29%; 11-50: 20%; 51-100: 12%], and overall expression [low: 84%; high: 16%]. High ERCC1 expression was associated with reduced RFS (6 vs. 10months; P=0.03) and decreased OS (9 vs. 18months; P=0.019). After accounting for adverse tumor factors, high ERCC1 expression persisted as a negative prognostic factor on multivariate Cox regression for both RFS and OS [hazards ratio (HR), 2.1; 95% confidence interval (CI), 1.1-3.9; P=0.02; HR, 3; 95% CI, 1.6-6; P=0.001, respectively]. A subset analysis of only those 73 patients who received adjuvant therapy revealed the same negative effect of high ERCC1 expression on RFS (4 vs. 15months; P=0.001) and OS (9 vs. 20months; P<0.001). Conclusions: Pancreas cancer exhibits differential expression of ERCC1. High ERCC1 expression is associated with both reduced RFS and OS after resection. ERCC1 expression levels may help to predict patient outcome with adjuvant chemotherapy. Society of Surgical Oncology, 2011 Maithel Shishir Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA aut Coban Ipek Department of Pathology, Emory University, Atlanta, GA, USA aut Kneuertz Peter Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA aut Kooby David Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA aut El-Rayes Bassel Department of Hematology and Oncology, Emory University, Atlanta, GA, USA aut Kauh John Department of Hematology and Oncology, Emory University, Atlanta, GA, USA aut Sarmiento Juan Department of Surgery, Division of General Surgery, Emory University, Atlanta, GA, USA aut Staley III Charles Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA aut Volkan Adsay N. Department of Pathology, Emory University, Atlanta, GA, USA aut Annals of Surgical Oncology Springer-Verlag 18/9(2011-09-01), 2699-2705 1068-9265 18:9<2699 2011 18 10434 https://doi.org/10.1245/s10434-011-1610-x text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1245/s10434-011-1610-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Maithel Shishir Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA aut NATIONALLICENCE 700 1- Coban Ipek Department of Pathology, Emory University, Atlanta, GA, USA aut NATIONALLICENCE 700 1- Kneuertz Peter Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA aut NATIONALLICENCE 700 1- Kooby David Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA aut NATIONALLICENCE 700 1- El-Rayes Bassel Department of Hematology and Oncology, Emory University, Atlanta, GA, USA aut NATIONALLICENCE 700 1- Kauh John Department of Hematology and Oncology, Emory University, Atlanta, GA, USA aut NATIONALLICENCE 700 1- Sarmiento Juan Department of Surgery, Division of General Surgery, Emory University, Atlanta, GA, USA aut NATIONALLICENCE 700 1- Staley III Charles Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA aut NATIONALLICENCE 700 1- Volkan Adsay N. Department of Pathology, Emory University, Atlanta, GA, USA aut NATIONALLICENCE 773 0- Annals of Surgical Oncology Springer-Verlag 18/9(2011-09-01), 2699-2705 1068-9265 18:9<2699 2011 18 10434 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer