Significance of RRM1 and ERCC1 expression in resectable pancreatic adenocarcinoma.
The identification of molecular markers, useful for therapeutic decisions in pancreatic cancer patients, is crucial for advances in disease management. Gemcitabine, although a cornerstone of current therapy, has limited efficacy. RRM1 is a key molecule for gemcitabine efficacy and is also involved in tumor progression. We determined in situ RRM1 and excision repair cross complementation group 1 (ERCC1) protein levels in 68 pancreatic cancer patients. All had R0 resections without preoperative therapy. Protein levels were determined by automated quantitative analysis (AQUA), a fluorescence-based immunohistochemical method. The relationship between protein expressions and clinical outcomes, including response to gemcitabine at the time of disease recurrence, was determined. Patients with high RRM1 showed significantly better overall survival than patients with low expression (P=0.0196). There was a trend toward better overall survival for patient with high ERCC1 (P=0.0552). When both markers were considered together, patients with both high RRM1 and ERCC1 faired the best in terms of overall and disease-free survival (P=0.0066, P=0.0127). In addition, treatment benefit from gemcitabine in patients with disease recurrence was observed only in patients with low RRM1. The combination of RRM1 and ERCC1 expression is prognostic in pancreatic cancer patients after a complete resection. On disease recurrence, only patients with low RRM1 derive benefit from gemcitabine.
Akita
H
H
Department of Surgery, Osaka University Graduate School of Medicine, Suita-city, Osaka, Japan.
Zheng
Z
Z
Takeda
Y
Y
Kim
C
C
Kittaka
N
N
Kobayashi
S
S
Marubashi
S
S
Takemasa
I
I
Nagano
H
H
Dono
K
K
Nakamori
S
S
Monden
M
M
Mori
M
M
Doki
Y
Y
Bepler
G
G
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004720:Endonucleases / Q000096:biosynthesis*; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000601:surgery; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D011379:Prognosis; D012262:Ribonucleoside Diphosphate Reductase; D016019:Survival Analysis; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D003841:Deoxycytidine; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; C071447:ERCC1 protein, human; D004720:Endonucleases; D000093542:Gemcitabine