Ribonucleotide reductase subunit M2 mRNA expression in pretreatment biopsies obtained from unresectable pancreatic carcinomas.
BACKGROUND
Gemcitabine is an efficacious cytotoxic agent used in the treatment of unresectable pancreatic carcinoma (PC). Recently, gemcitabine resistance has been associated with the ribonucleotide reductase subunit M2 (RRM2). In this prospective study, we hypothesized that RRM2 expression in PC biopsy specimens would be a significant predictor of outcome.


METHODS
RRM2 mRNA expression in 35 endoscopic ultrasonography-guided fine needle aspiration biopsy (EUS-FNAB) samples was quantified using real-time quantitative reverse transcription-polymerase chain reaction.


RESULTS
Thirty-one of 35 biopsy specimens could be assessed for RRM2 expression levels. The mean RRM2 expression relative to glyceraldehyde-3-phosphate dehydrogenase was 0.248 (range, 0.00739 to 0.858). Eighteen patients (64.5%) had low RRM2 levels, and 13 patients (35.5%) had high RRM2 levels with a cutoff of 0.1. The median survival was 8.8 months for patients with low RRM2 levels and 5.0 months for patients with high levels (P < 0.05). In the low RRM2 expression group, a complete response (CR) was observed in one patient, and a partial response (PR) was observed in eight patients. In contrast, in the high RRM2 expression group, PR was observed in one patient, and CR was not observed. The overall response rate between the high and low expression groups was significantly different (50.0% vs. 7.7%, P < 0.05).


CONCLUSIONS
RRM2 mRNA expression of EUS-FNAB specimens is a key predictive marker of survival in gemcitabine-treated patients with PC.
Itoi
Takao
T
Fourth Department of Internal Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Tokyo 160-0023, Japan.
Sofuni
Atsushi
A
Fukushima
Noriyoshi
N
Itokawa
Fumihide
F
Tsuchiya
Takayoshi
T
Kurihara
Toshio
T
Moriyasu
Fuminori
F
Tsuchida
Akihiko
A
Kasuya
Kazuhiko
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D044963:Biopsy, Fine-Needle; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D021122:Protein Subunits; D012333:RNA, Messenger / Q000235:genetics; D012262:Ribonucleoside Diphosphate Reductase / Q000235:genetics / Q000378:metabolism*; D016019:Survival Analysis; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D021122:Protein Subunits; D012333:RNA, Messenger; D003841:Deoxycytidine; C093713:ribonucleotide reductase M2; D012262:Ribonucleoside Diphosphate Reductase; D000093542:Gemcitabine