Mutations of p53 and K-ras correlate TF expression in human colorectal carcinomas: TF downregulation as a marker of poor prognosis.
Int J Colorectal Dis
; 26(5): 593-601, 2011 May.
Article
in En
| MEDLINE
| ID: mdl-21404058
ABSTRACT
BACKGROUND:
Tissue factor (TF) is emphasized as the promising target in the future targeted therapy strategy for colorectal cancer (CRC). Recent evidence showed that TF expression is under the control of K-ras and p53. However, a comprehensive evaluation of TF expression, K-ras status, and p53 mutation has not been systematically analyzed. The aims of this study were to identify the percentages of positive TF in CRC patients; analyze the associations of TF expression, K-ras status, and p53 mutation; and evaluate the prognostic value of TF in CRC patients.METHODS:
Ninety-six CRC samples were tested for TF expression, p53 mutation, and K-ras status by semiquantitative immunohistochemistry, Western blotting analysis, direct sequencing, and real-time quantitative PCR. Associations were sought with TF expression and clinical outcomes.RESULTS:
TF expression was related to clinical stages, tumor differentiation, and tumor size. The positive proportions of TF expression on tumor cells and tumor vascular endothelial cells were 70% and 53% respectively in CRC patients. The positive proportion of TF co-expression on both cancer cells and tumor vascular endothelial cells was 40%, compared to an 83% total TF positive proportion in CRC patients. TF expression on CRC appeared to be increased with K-ras and/or p53 mutation(s). Disease-free survival and overall survival were significantly reduced in CRC patients with high TF expression.CONCLUSIONS:
TF may participate in both K-ras and p53 mutations involved in colorectal carcinogenesis and could be considered as a prognostic indicator for patients CRC.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thromboplastin
/
Colorectal Neoplasms
/
Biomarkers, Tumor
/
Down-Regulation
/
Tumor Suppressor Protein p53
/
Proto-Oncogene Proteins
/
Ras Proteins
/
Mutation
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Int J Colorectal Dis
Journal subject:
GASTROENTEROLOGIA
Year:
2011
Type:
Article
Affiliation country:
China