Specific TP53 and/or Ki-ras mutations as independent predictors of clinical outcome in sporadic colorectal adenocarcinomas: results of a 5-year Gruppo Oncologico dell'Italia Meridionale (GOIM) prospective study.
BACKGROUND
Although Ki-ras and TP53 mutations have probably been the genetic abnormalities most exhaustively implicated and studied in colorectal cancer (CRC) progression, their significance in terms of disease relapse and overall survival has not yet clearly been established.


METHODS
A prospective study was carried out on paired tumor and normal colon tissue samples from a consecutive series of 160 previously-untreated patients, undergoing resective surgery for primary operable sporadic CRC. Mutations within the TP53 (exons 5-8) and Ki-ras (exon 2) genes were detected by PCR-SSCP analyses following sequencing.


RESULTS
Mutation analyses of exons 5 to 8 of the TP53 gene showed mutations in 43% (68/160) of the cases, while mutation analyses of exon 2 of the Ki-ras gene showed mutations in 46% (74/160) of the cases. Multivariate analyses showed that clinical outcome were strongly associated with the presence of specific TP53 mutations in L3 domain alone (only in DFS) or in combination with specific Ki-ras mutations at codon 13.


CONCLUSIONS
Specific TP53 mutations in L3 domain alone (only in DFS) or in combination with specific Ki-ras mutations at codon 13 are associated with a worse prognosis in sporadic CRC.
Bazan
V
V
Department of Oncology-Regional Reference Center for the Biomolecular Characterization of Neoplasms and Genetic Screening of Hereditary Tumors, Institute of Experimental Medicine, Institute of Pathology, Università di Palermo, Palermo, Italy.
Agnese
V
V
Corsale
S
S
Calò
V
V
Valerio
M R
MR
Latteri
M A
MA
Vieni
S
S
Grassi
N
N
Cicero
G
G
Dardanoni
G
G
Tomasino
R M
RM
Colucci
G
G
Gebbia
N
N
Russo
A
A
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000556:secondary / Q000601:surgery; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D007978:Levamisole / Q000008:administration & dosage; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009367:Neoplasm Staging; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D018631:ras Proteins / Q000235:genetics*
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D007978:Levamisole; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D002955:Leucovorin; D005472:Fluorouracil