Prognostic significance of K-ras and TP53 mutations in the role of adjuvant chemotherapy on survival in patients with Dukes C colon cancer.
OBJECTIVE
Mutations in K-ras and TP53 genes are common in colorectal cancer. They affect biologic behavior and might influence chemotherapy susceptibility in these tumors. We investigated whether the survival of patients with Dukes C colon cancer treated with adjuvant chemotherapy is influenced by K-ras and TP53 mutations.


METHODS
Mutation screening of the hot spots of the K-ras gene and of the evolutionarily conserved regions of the TP53 gene was performed by denaturing gradient gel electrophoresis technique in formalin-fixed paraffin-embedded specimens of 55 consecutive patients with Dukes C colon cancer treated with adjuvant 5-fluorouracil-based chemotherapy. The median follow-up was 47 (range, 32-66) months.


RESULTS
Alterations in the mutation hot spots of K-ras were found at codon 12 (n = 11) and 13 (n = 4) in 15 of the 55 carcinomas (27 percent). No mutation was found at codon 61. Mutations of a probably causative nature in the evolutionarily conserved regions (exons 5-8) of the TP53 gene were found in 24 tumors (44 percent). K-ras and TP53 mutations were found equally in the group with recurrent disease (7/26 (26 percent) and 12/27 (44 percent), respectively) and in the group without recurrences (8/28 (24 percent) and 12/28 (43 percent), respectively). Cancer-specific survival did not differ significantly between patients with K-ras or TP53 or both mutated and nonmutated tumors, respectively (log-rank test: K-ras, P = 0.72 and TP53, P = 0.77; K-ras and TP53, P = 0.8). Also, potentially aggressive K-ras codon 12 and 13 mutations had the same survival as tumors without these mutations (log-rank test; P = 0.73).


CONCLUSIONS
Patients with K-ras or TP53 or both mutated Dukes C colon tumors have the same survival as nonmutated tumors when treated with adjuvant chemotherapy. These data suggest that mutations in K-ras or TP53 alone are not prognostic indicators in patients with Dukes C colon cancer receiving adjuvant 5-Fluorouracil-based therapy.
Bleeker
W A
WA
Department of Surgery/Surgical Oncology, University Hospital Groningen, The Netherlands.
Hayes
V M
VM
Karrenbeld
A
A
Hofstra
R M
RM
Verlind
E
E
Hermans
J
J
Poppema
S
S
Buys
C H
CH
Plukker
J T
JT
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003062:Codon; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D003131:Combined Modality Therapy; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D003062:Codon; D016159:Tumor Suppressor Protein p53; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D005472:Fluorouracil