Colorectal carcinoma prognosis can be predicted by alterations in gene p53 exons 5 and 8.
OBJECTIVE
Gene p53 alteration is a genetic event described in the progression from adenoma to colorectal carcinoma. Most of the p53 mutations occur in exons 5 to 8 in highly preserved regions and in the three main structural domains of the p53 protein. It is possible that mutations affecting different structural regions may present different effects on the p53 protein function and, due to this, they may have different prognostic meaning.


METHODS
The study population consisted of 353 patients diagnosed with sporadic colorectal cancer. Mutations in 5-8 exons of p53 gene were detected by means of single strand conformation polymorphism (SSCP). All samples that showed different migration bands in SSCP were confirmed by sequencing.


RESULTS
A total of 69 patients (19.7%) showed alterations of the gene p53. It was observed that mutation in codon 175 in exon 5 was related to tumors located in the colon (p = 0.01) and the mutation in the codon 288 in exon 8 was related to rectal tumors (p = 0.02). In the study of overall survival, mutation in codon 175 of exon 5 conferred a better prognosis and alterations of exon 8 were related to a worse prognosis in different population subgroups: in men, in patients younger than 71 years old, in the tumors located in the proximal colon, the ones moderately differentiated, and those that are mucinous.


CONCLUSIONS
According to this study, mutations in different exons of p53 are related to different phenotypes in colorectal cancer. These phenotypes could mean differences in the clinical evolution of the patients.
Vidaurreta
M
M
Department of Clinical Analysis, Hospital Clínico San Carlos, Madrid, Spain.
Maestro
M L
ML
Sanz-Casla
M T
MT
Rafael
S
S
Veganzones
S
S
de la Orden
V
V
Cerdán
J
J
Arroyo
M
M
Torres
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005091:Exons / Q000235:genetics*; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D015996:Survival Rate