Prognostic value of ERCC1, thymidylate synthase, and glutathione S-transferase pi for 5-FU/oxaliplatin chemotherapy in advanced colorectal cancer.
BACKGROUND
The aim of this study was to determine whether the expression of the excision repair cross-complementing 1 (ERCC1), thymidylate synthase (TS) and glutathione S-transferase pi (GSTpi) predict clinical outcome in patients with advanced colorectal cancer treated with fluorouracil (5-FU)/oxaliplatin chemotherapy.


METHODS
The study population consisted of 70 patients with advanced colorectal cancer (median age, 54 years). Patients were treated with oxaliplatin 85 mg/m as a 2-hour infusion on days 1 plus leucovorin (LV) 20 mg/m over 10 minutes, followed by 5-FU bolus 400 mg/m and a 22-hour continuous infusion of 600 mg/m from day 1 to 2. Treatment was repeated at 2-week intervals. The expression of ERCC1, TS, and GSTpi in primary tumors was examined using immunohistochemistry.


RESULTS
ERCC1, TS, and GSTpi were positive in 55.7%, 68.6%, and 71.4% of cases, respectively. Patients without TS expression were more likely to respond to chemotherapy (P = 0.009). There were no significant differences between response to treatment and the ERCC1 or GSTpi expression pattern (P = 0.768, P = 0.589, respectively). The median overall survival (OS) was significantly longer in patients without ERCC1 expression (P = 0.0474). Patients who were ERCC1 positive combined with TS positive, or those with ERCC1 positive combined with TS positive and GSTpi positive had a poor OS (P = 0.0017, P = 0.0323, respectively). Multivariate analysis revealed that both ERCC1 and TS expression significantly impacted OS (hazard ratio 1.72, P = 0.023).


CONCLUSIONS
Immunohistochemical study of ERCC1 and TS may be useful for the prediction of clinical outcome in patients with advanced colorectal cancer treated with 5-FU and oxaliplatin.
Kim
Sung-Hyun
SH
Department of Internal Medicine, Dong-A University College of Medicine, Busan, South Korea.
Kwon
Hyuk-Chan
HC
Oh
Sung Yong
SY
Lee
Dong Mee
DM
Lee
Suee
S
Lee
Jong-Hoon
JH
Roh
Mee-Sook
MS
Kim
Dae-Cheol
DC
Park
Ki-Jae
KJ
Choi
Hong-Jo
HJ
Kim
Hyo-Jin
HJ
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000556:secondary; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004720:Endonucleases / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D051549:Glutathione S-Transferase pi / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000556:secondary; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D013940:Thymidylate Synthase / Q000378:metabolism*; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D013940:Thymidylate Synthase; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; C071447:ERCC1 protein, human; D004720:Endonucleases; D005472:Fluorouracil