p53 alteration is not an independent prognostic indicator, but affects the efficacy of adjuvant chemotherapy in human pancreatic cancer.

Abstract

BACKGROUND AND OBJECTIVES:

Mutations in the p53 gene are found in more than 50% of human cancers and are observed in 60-80% of pancreatic cancers. The clinicopathologic implications of p53 abnormalities and their effects on the efficacy of the adjuvant chemotherapy for pancreatic cancer remain controversial.

METHODS:

We investigated the p53 status in core exon-4 to -9 (codon 33-331) by direct DNA sequencing in a series of 72 pancreatic cancers and analyzed the effects of p53 abnormalities on the patients' survival and the efficacy of adjuvant chemotherapy.

RESULTS:

p53 mutations were found in 62.5% (45/72) of cases, including 38 point mutations and 7 frameshift mutations. The subtypes of p53 mutations included 68.9% (31/45) transitions and 15.6% (7/45) transversions. 39.5% (15/38) of point mutations were CGT (Arg) to CAT (His) mutation at codon-273 of exon-8. 34.2% (13/38) of point mutations were CGG (Arg) to TGG (Trp) mutation at codon-248 of exon-7. Of seven frameshift mutations, four were seen at exon-4, two at exon-5, and one at exon-6. Of overall cases, p53 abnormalities were not associated with a poorly differentiated grade and an advanced stage. The relationship of adjuvant chemotherapy to survival is approaching statistical significance. Univariate analysis showed that in the p53 mutation group, the patients who received adjuvant chemotherapy had a better survival ratio than that of patients who did not do. Multivariate analysis indicated that in the group with p53 mutations, the significant factors for survival were adjuvant chemotherapy, histologic grade, and clinical stage. However, in the group with a wild-type p53 gene, only histologic grade was a significant factor. In addition, 34.7% (25/72) of the cases harbor p53 polymorphism mutation only at codon-72 of exon-4, which did not show any significant effect on the pathology, prognosis, and efficacy of adjuvant chemotherapy of the pancreatic cancers.

CONCLUSIONS:

A p53 abnormality was not an independent factor for evaluating the prognosis of patients with pancreatic cancer, but was a beneficial indicator for selecting a reasonable strategy of adjuvant chemotherapy against pancreatic cancer.

• Authors: Ming Dong, Yoshinori Nio, Kunihiro Yamasawa, Tomoko Toga, Lishuang Yue, Takayuki Harada
• Journal: Journal of surgical oncology (J Surg Oncol) Vol. 82 Issue 2 Pg. 111-20 (Feb 2003) ISSN: 0022-4790 [Print] United States
• PMID: 12561067 (Publication Type: Journal Article)
• Copyright: Copyright 2003 Wiley-Liss, Inc.

Chemical References

• Antineoplastic Agents

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (therapeutic use)
• Carcinoma, Pancreatic Ductal (drug therapy, genetics, surgery)
• Chemotherapy, Adjuvant (methods)
• Female
• Gene Amplification
• Genes, p53 (genetics)
• Humans
• Male
• Middle Aged
• Mutation (genetics)
• Pancreatectomy (methods)
• Pancreatic Neoplasms (drug therapy, genetics, surgery)
• Polymerase Chain Reaction
• Polymorphism, Genetic
• Prognosis
• Sequence Analysis, DNA
• Survival Analysis
• Treatment Outcome