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Background  Although postoperative chemotherapy is widely accepted as the standard modality for Dukes' stage C or earlier stage colorectal cancer (CRC) patients, biomarkers to predict those who may benefit from the therapy have not been identified. Previous  in vitro  and clinical investigations reported that CRC patients with wild-type p53 gene ( TP53) -tumors benefit from 5-fluorouracil (5-FU) based chemotherapy, while those with mutated  TP53 -tumors do not. However, these studies evaluated the mutation-status of  TP53  by immunohistochemistry with or without single-strand conformation polymorphism, and the mutation frequency was different from study to study. In addition, the polymorphic status at p53 codon 72, which results in arginine or proline residues (R72P) and is thought to influence the function of the protein significantly, was not examined.    Methods  To evaluate the significance of the  TP53  mutation as a molecular marker to predict the prognosis of CRC patients, especially those who received postoperative chemotherapy, we examined the mutation by direct sequencing from fresh CRC tumors and evaluated the R72P polymorphism of the mutated  TP53  by a combined mutant allele- and polymorphic allele-specific polymerase chain reaction (PCR).    Results  The  TP53  mutation occurred in 147 (70%) of 211 Japanese CRC tumors. The mutation was observed in 93 (63%) tumors on the R72 allele and in 54 (37%) tumors on the P72 allele. Although the alterations to  TP53  have no prognostic significance for CRC patients overall, we found that Dukes' stage C CRC patients who did not receive postoperative chemotherapy and carried the mutated  TP53 -R72 showed significantly longer survival times than those with the mutated  TP53 -P72 when evaluated by overall survival ( p = 0.012 ).    Conclusion  Using a combined mutant allele- and polymorphic allele-specific PCR, we defined the codon 72 polymorphic status of the  TP53  mutated allele in Japanese CRC patients. We raised a possibility that Dukes' stage C colorectal cancer patients with tumors carrying  TP53  mutation, especially the P72 allele, benefited from 5-FU based postoperative chemotherapy.

bmc cancer

Identification of colorectal cancer patients with tumors carrying the TP53mutation on the codon 72 proline allele that benefited most from 5-fluorouracil (5-FU) based postoperative chemotherapy