p53 mutations as a possible predictor of response to chemotherapy in metastatic colorectal carcinomas.
Although intrahepatic infusion therapy with 5-fluorouracil for unresectable colorectal liver metastases may lead to improved overall survival for some patients, it is not clear why a response is not observed in others. Gene alterations in oncogenes or tumor-suppressor genes are critical events in tumor formation, and some of them could play a role in the process of drug resistance. The tumor-suppressor gene p53, which is known to trigger cell arrest or apoptosis in response to DNA damage, is found to be mutated in a wide range of human tumors. The aim of this work is to establish whether a relationship is found between p53 mutations and survival in patients undergoing adjuvant chemotherapy for advanced Dukes' D colorectal cancers. Seventeen tumors from patients treated with 5-fluorouracil regimen via intrahepatic infusion for unresectable colorectal hepatic metastasis were considered. p53 mutations from tumor DNA were detected, after amplification by PCR of exons 5 to 8, by non-radioactive single-strand conformation polymorphism and direct DNA sequencing. Patients with mutated p53 colorectal tumors had short survival, whereas prolonged survival was associated with the presence of wild-type p53 (p = 0.019). Our data suggest that mutated p53 colorectal tumors had a weak response, or even no response, to chemotherapeutic treatment. Routine assessment of p53 status would be helpful in selecting patients with only wild-type p53 gene who have a predictably better response to chemotherapy.
Benhattar
J
J
Institute of Pathology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Cerottini
J P
JP
Saraga
E
E
Metthez
G
G
Givel
J C
JC
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics* / Q000601:surgery; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000601:surgery; D003131:Combined Modality Therapy; D005472:Fluorouracil / Q000627:therapeutic use*; D016158:Genes, p53; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary*; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D011237:Predictive Value of Tests; D011379:Prognosis
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil