Ribonucleotide Reductase M2 Is Not Predictive of Adjuvant Gemcitabine Treatment Benefit in Patients with Resected Pancreatic Adenocarcinoma
Hao Xie, Jingmei Lin, Dafydd G Thomas, Wei Jiang, Xiuli Liu. Cleveland Clinic, Cleveland; Indiana University, Indianapolis; University of Michigan, Ann Arbor
Background: Gemcitabine is used widely as an adjuvant treatment for pancreatic adenocarcinoma. Ribonucleotide reductase small subunit M2 (RRM2), the catalytic subunit of ribonucleotide reductase, is associated with tumor progression and resistance to gemcitabine. Recent studies showed that low mRNA expression of RRM2, was predictive of treatment benefit of gemcitabine in patients with resected pancreatic adenocarcinoma (Fujita H et al., Neoplasia 12: 807-17, 2010). This study aims to determine if RRM2 protein expression level assessed by immunohistochemistry is 1) prognostic in patients with resectable pancreatic adenocarcinoma and 2) a predictive marker for treatment benefit of gemcitabine.
Design: 117 patients underwent pancreatic resection for pancreatic adenocarcinoma were included. 44 of them received adjuvant gemcitabine treatment prior to disease recurrence/metastases. Tissue micro-arrays were constructed from paraffin-embedded tumors. RRM2 expression in tumors was determined by immunohistochemistry and grouped as negative or positive. The correlation of RRM2 expression and overall survival (OS) or progression-free survival (PFS) was determined using the Kaplan-Meier method. Cox's proportion hazards multivariate model was also employed to identify prognostic factors.
Results: RRM2 expression showed no prognostic value in the entire group regarding OS (median OS 30.9 vs 13.7 months, p=0.26) and PFS (median OS 20.6 vs 11.8 months, p=0.46). RRM2 expression was not predictive of OS and PFS in the subgroup of 44 patients who received gemcitabine treatment as an adjuvant therapy either (median OS 31.2 vs 15.2 months, p=0.62; median PFS 11.3 vs 14 months, p=0.35, respectively). Cox's proportion hazards multivariate model showed no prognostic effect of RRM2 expression on OS (HR 0.89, p=0.76) and PFS (HR 1.45, p=0.44) in the subgroup of 44 patients who received gemcitabine therapy. However, the number of positive lymph nodes and perineural invasion are prognostic factor for OS (HR 1.21, p=0.01) and for PFS (HR 5.44, p=0.001), respectively.
Conclusions: RRM2 protein expression level determined by immunohistochemistry on paraffin-embedded pancreatic carcinoma tissue is neither prognostic nor predictive of adjuvant gemcitabine treatment benefit in patients with resectable pancreatic adenocarcinoma.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 283, Tuesday Afternoon