The predictive value of p53 and p33(ING1b) in patients with Dukes'C colorectal cancer.
OBJECTIVE
Identification of biological markers that may predict response to chemotherapy would allow the individualization of treatment by enabling selection of patients most likely to benefit from chemotherapy. The aims of this study were to determine whether p53 mutation status and p53 and p33(ING1b) protein expression can predict which patients with Dukes' C colorectal cancer following curative surgical resection respond to adjuvant chemotherapy with 5-fluorouracil (5-FU).


METHODS
Patients with Dukes'C colorectal cancer (n = 41) were studied. DNA was extracted and analysed for p53 mutation using PCR-based direct DNA sequencing. Tumours were analysed for p53 protein expression by immunohistochemistry using DO-7 monoclonal antibody and for p33(ING1b) protein expression using GN1 monoclonal antibody.


RESULTS
There was a significant association between p53 mutation status analysed by gene sequencing and overall and metastasis-free survival (P = 0.03 and 0.004, respectively, log-rank test). By contrast, no significant correlation was found between p53 and p33(ING1b) protein expression and overall or metastasis-free survival.


CONCLUSIONS
In patients with Dukes'C colorectal cancer who underwent curative surgical resection of the primary tumour, followed by 5-FU-based adjuvant chemotherapy, p53 mutation status as assessed by gene sequencing is a significant predictor of overall and metastasis-free survival.
Ahmed
I A M
IA
Bishop Auckland General Hospital, Bishop Auckland, County Durham, UK.
Kelly
S B
SB
Anderson
J J
JJ
Angus
B
B
Challen
C
C
Lunec
J
J
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant / Q000379:methods; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000145:classification / Q000188:drug therapy* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism*; D011237:Predictive Value of Tests; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; C501503:ING1 protein, human; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D005472:Fluorouracil