Prognostic value of thymidylate synthase, Ki-67, and p53 in patients with Dukes' B and C colon cancer: a National Cancer Institute-National Surgical Adjuvant Breast and Bowel Project collaborative study.
OBJECTIVE
To define the value of thymidylate synthase (TS), Ki-67, and p53 as prognostic markers in patients with stage II and III colon carcinoma.


METHODS
We retrospectively analyzed the prognostic value of TS, Ki-67, and p53 in 706 patients with Dukes' B (291 patients) or Dukes' C (415 patients) colon carcinoma who were treated with either surgery alone (275 patients) or surgery plus fluorouracil (FU)-leucovorin chemotherapy (431 patients) in National Surgical Adjuvant Breast and Bowel Project (NSABP) protocols C01-C04. All three markers were assayed using immunohistochemical techniques.


RESULTS
Using 5 years of follow-up data, our retrospective analysis demonstrated an association between TS intensity (relapse-free survival [RFS]: risk ratio [RR] = 1.46, P =.01; overall survival [OS]: RR = 1.54, P =.002), Ki-67 (RFS: RR = 0.76, P =.05; OS: RR = 0.62, P =.001), and p53 (RFS: RR = 1.49, P =.01; OS: RR = 1.21, P =.18) for RFS and OS. High TS intensity levels and positive p53 staining were associated with a worse outcome. Tumors containing a high percentage of Ki-67-positive cells enjoyed an improved outcome compared with those patients whose tumors contained relatively few positive cells. An interaction with treatment was not identified for any of the markers.


CONCLUSIONS
This retrospective investigation demonstrated that TS, Ki-67, and p53 staining each had significant prognostic value for patients with Dukes' B and C colon carcinoma. However, none of the markers could be used to clearly discern groups of individuals who would be predicted to derive greater or lesser benefit from the use of adjuvant chemotherapy.
Allegra
Carmen J
CJ
Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-2440, USA. allegrac@navmed.nci.nih.gov
Paik
Soon
S
Colangelo
Linda H
LH
Parr
Allyson L
AL
Kirsch
Ilan
I
Kim
George
G
Klein
Pamela
P
Johnston
Patrick G
PG
Wolmark
Norman
N
Wieand
H Samuel
HS
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D003082:Colectomy; D003110:Colonic Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000628:therapy; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000032:analysis*; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D013940:Thymidylate Synthase / Q000032:analysis*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D013940:Thymidylate Synthase; D002955:Leucovorin; D005472:Fluorouracil