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


CONCLUSIONS
RRM2 protein expression in pancreatic adenocarcinoma is neither prognostic nor predictive of adjuvant gemcitabine benefit in patients with resectable pancreatic adenocarcinoma.
Anatomic Pathology, Cleveland Clinic, Cleveland, OH 44195, USA.
Hao
H
Xie
Jingmei
J
Lin
Dafydd G
DG
Thomas
Wei
W
Jiang
Xiuli
X
Liu
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D021441:Carcinoma, Pancreatic Ductal / Q000201:enzymology / Q000401:mortality / Q000556:secondary / Q000601:surgery*; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009820:Ohio; D010180:Pancreatectomy / Q000009:adverse effects / Q000401:mortality; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D016612:Paraffin Embedding; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012262:Ribonucleoside Diphosphate Reductase / Q000032:analysis*; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; C093713:ribonucleotide reductase M2; D012262:Ribonucleoside Diphosphate Reductase; D000093542:Gemcitabine