Molecular detection of TP53, Ki-Ras and p16INK4A promoter methylation in plasma of patients with colorectal cancer and its association with prognosis. Results of a 3-year GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.
BACKGROUND
Despite the improvement in detection and surgical therapy in the last years, the outcome of patients affected by colorectal carcinoma (CRC) remains limited by metastatic relapse. The aim of this study was to investigate the presence of free tumor DNA in the plasma of CRC patients in order to understand its possible prognostic role.


METHODS
Ki-Ras, TP53 mutations and p16(INK4A) methylation status were prospectively evaluated in tumor tissues and plasma of 66 CRC patients.


RESULTS
In 50 of the 66 primitive tumor cases (76%) at least one significant alteration was identified in Ki-Ras and/or TP53 and/or p16(INK4A) genes. Eighteen of the 50 patients presented the same alteration both in the plasma and in the tumor tissue. At univariate analysis, Ki-Ras mutations proved to be significantly related to quicker relapse (P <0.01), whereas only a trend towards statistical significance (P = 0.083) was observed for the TP53 mutations


CONCLUSIONS
Detection of Ki-Ras and TP53 mutation in plasma should be significantly related to disease recurrence. These data suggest that patients with a high risk of recurrence can be identified by means of the analysis of tumor-derived plasma DNA with the use of fairly non-invasive techniques.
Bazan
V
V
Section of Medical Oncology and Section of Surgical Oncology, Department of Surgical and Oncology, Università di Palermo, Italy.
Bruno
L
L
Augello
C
C
Agnese
V
V
Calò
V
V
Corsale
S
S
Gargano
G
G
Terrasi
M
M
Schirò
V
V
Di Fede
G
G
Adamo
V
V
Intrivici
C
C
Crosta
A
A
Rinaldi
G
G
Latteri
F
F
Dardanoni
G
G
Grassi
N
N
Valerio
M R
MR
Colucci
G
G
Macaluso
M
M
Russo
A
A
D000368:Aged; D015179:Colorectal Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D005260:Female; D019942:Genes, p16; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D011401:Promoter Regions, Genetic; D011446:Prospective Studies
D004273:DNA, Neoplasm