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Int J Clin Exp Pathol 2012;5(4):347-355

Original Article
Ribonucleotide reductase M2 does not predict survival in patients with resectable
pancreatic adenocarcinoma

Hao Xie, Jingmei Lin, Dafydd G Thomas, Wei Jiang, Xiuli Liu

Anatomic Pathology, Cleveland Clinic, Cleveland, OH; Cleveland Clinic Lerner College of Medicine of Case Western Reserve University,
Cleveland, OH; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN; Departments of
Pathology, University of Michigan Health System, Ann Arbor, MI, USA.

Received March 28, 2012; accepted April 13, 2012; Epub April 16, 2012; Published May 30, 2012

Abstract: Background: Ribonucleotide reductase M2 (RRM2) was associated with pancreatic tumor progression and resistance to
gemcitabine. This study aimed to determine if RRM2 protein expression was prognostic in patients with resectable pancreatic
adenocarcinoma and predictive of adjuvant gemcitabine benefit. Methods: 117 patients underwent tumor resection for pancreatic
adenocarcinoma from 10/1999 to 12/2007. We constructed tissue microarrays from paraffin-embedded tumors and determined RRM2 protein
expression using immunohistochemistry and grouped as negative or positive. We estimated overall survival (OS) and progression-free survival
(PFS) using the Kaplan-Meier method and examined the prognostic and predictive value of RRM2 expression using Cox proportional hazards
model. Results: RRM2 expression showed no prognostic value in the entire group regarding OS (median OS 30.9 months in RRM2-positive
versus 13.7 months in RRM2-negative, P = 0.26) and PFS (median OS 20.6 months in RRM2-positive versus 11.8 months in RRM2-negative, P
= 0.46). RRM2 expression did not predict adjuvant gemcitabine benefit in the subgroup of 44 patients who received gemcitabine therapy
(median OS 31.2 versus 15.2 months, P = 0.62; median PFS 11.3 versus 14.0 months, P = 0.35). Cox proportional hazards regression showed
no prognostic effect of RRM2 expression on OS and PFS in the subgroup of 44 patients. However, the number of positive lymph nodes and
perineural invasion were prognostic factors for OS (HR 1.2, P = 0.005) and for PFS (HR 5.5, P = 0.007), respectively. Conclusion: RRM2 protein
expression in pancreatic adenocarcinoma is neither prognostic nor predictive of adjuvant gemcitabine benefit in patients with resectable
pancreatic adenocarcinoma.

Keywords: Ribonucleotide reductase M2, pancreatic cancer, resectable, gemcitabine

Address all correspondence to:
Dr. Xiuli Liu
Department of Anatomic Pathology
Cleveland Clinic
9500 Euclid Avenue/L25
Cleveland, Ohio 44195, USA.
Tel: 216-445-8745; Fax: 216-445-6967
E-mail: liux3@ccf.org