title: High expression of survivin is prognostic of shorter survival but not predictive of adjuvant gemcitabine benefit in patients with resected pancreatic adenocarcinoma.
abstract: Overexpression of survivin has been associated with gemcitabine resistance in pancreatic adenocarcinoma, but previous studies have shown conflicting results. This study aims to determine its prognostic value in resected pancreatic adenocarcinoma with or without adjuvant therapy and its predictive value in adjuvant gemcitabine benefit in patients with resected pancreatic adenocarcinoma. This study included 118 patients who underwent pancreaticoduodectomy from 1999 to 2007, with no neoadjuvant chemoradiation. Forty-five patients received adjuvant gemcitabine. Survivin expression was assessed immunohistochemically and was graded as low (≤10% positive cells) and high (>10% positive cells) by recursive partitioning analysis. Prognostic factors, including tumor size, number of positive lymph nodes, perineural invasion, and stage, were identified for overall survival (OS) and progression-free survival (PFS) using Cox proportional hazards models. Multivariable analysis of the entire cohort revealed that both high survivin expression and perineural invasion predict significantly shorter OS (hazard ratio [HR] 2.0, p=0.01; HR 1.9, p=0.01, respectively) and shorter PFS (HR 1.9, p=0.04; HR 3.1, p=0.0006, respectively). Expression of survivin predicts neither OS nor PFS in patients treated with adjuvant gemcitabine. In summary, high expression of survivin is associated with shorter OS and PFS in patients with resected pancreatic adenocarcinoma after adjusting for other histopathological factors. However, survivin has no predictive value of adjuvant gemcitabine benefit.
authors.affiliation: Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Xie
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Shu-Yuan
authors.initials: SY
authors.lastname: Xiao
authors.forename: Xiuli
authors.initials: X
authors.lastname: Liu
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D000077022:Survivin; D015854:Up-Regulation; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D003841:Deoxycytidine; D000093542:Gemcitabine