Low Expression of Ribonucleotide Reductase M1 (RRM1) Determined by Quantitative Reverse Transcription-PCR (QRT-PCR) Is Predictive of Adjuvant Gemcitabine Treatment Benefit in Patients with Resectable Pancreatic Adenocarcinoma: A Pilot Study
W Jiang, A Tan, J Jiang, Y Wang, R Kim, JF Palma, Y Zhang, X Liu. Cleveland Clinic Foundation, Cleveland, OH; Johnson & Johnson Company, San Diego, CA
Background: Gemcitabine (2', 2'-difluorodeoxycytidine) has been a cornerstone of current chemotherapy for pancreatic cancer. Recent studies showed low expression of RRM1, the regulatory subunit of ribonucleotide reductase, determined by immunohistochemistry, was predictive of treatment benefit of gemcitabine in patients with resectable pancreatic adenocarcinoma in a palliative setting. However, whether or not the expression of RRM1 is predictive of treatment benefit of gemcitabine in an adjuvant setting in patients with resectable pancreatic adenocarcinoma has not been reported. This study aims to determine if RRM1 expression level is a predictive marker for treatment benefit of gemcitabine used as an adjuvant treatment for pancreatic adenocarcinoma.
Design: 179 consecutive patients underwent pancreatoduodenectomy at our institution for resectable pancreatic adenocarcinoma from 10/1999 to 12/2006. Total RNA was isolated from micro-dissected paraffin-embedded tumors in 84 patients. 18 of them received adjuvant gemcitabine treatment prior to disease recurrence/metastases. The expression of RRM1 in tumors was determined by QRT-PCR and the expression levels were normalized to two endogenous reference genes. The correlation of RRM1 expression levels and overall survival (OS) was determined using the Kaplan-Meier method. Cox's proportion hazards multivariate model was employed to examine the association of RRM1 expression with OS and Progression Free Survival (PFS).
Results: RRM1 expression did not have prognostic value in the entire group of patients regarding OS. However, in the subgroup of 18 patients who received gemcitabine treatment as an adjuvant treatment, patients with low RRM1 expression had significantly better overall survival (median survival 40 months vs. 23 months, p=0.022; hazard ratio 0.55, p=0.038).
Conclusions: Low RRM1 expression determined by QRT-PCR on paraffin-embedded pancreatic carcinoma tissue in patients who received gemcitabine as an adjuvant treatment predicts an overall survival benefit. Further large prospective studies are warranted to confirm the current finding and to provide guidance for individualized chemotherapy regimen.
Category: Liver & Pancreas
Tuesday, March 23, 2010 2:00 PM
Platform Session: Section C, Tuesday Afternoon