Mutations of p53 and K-ras correlate TF expression in human colorectal carcinomas: TF downregulation as a marker of poor prognosis

• Published in: International journal of colorectal disease Vol. 26; no. 5; pp. 593 - 601
• Main Authors: Rao, Benqiang, Gao, Yuanhong, Huang, Jun, Gao, Xiaoyan, Fu, Xinhui, Huang, Meijin, Yao, Jiayin, Wang, Jingping, Li, Wanglin, Zhang, Junxiao, Liu, Huanliang, Wang, Lei, Wang, Jianping
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01-05-2011; Springer; Springer Nature B.V
• Subjects: Analysis; Biological and medical sciences; Biomarkers, Tumor - genetics; Cancer; Care and treatment; Colorectal cancer; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Disease-Free Survival; Down-Regulation - genetics; Female; Gastroenterology; Gastroenterology. Liver. Pancreas. Abdomen; Genetic aspects; Health aspects; Hepatology; Humans; Immunohistochemistry; Internal Medicine; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Mutation - genetics; Original Article; Proctology; Prognosis; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins p21(ras); ras Proteins - genetics; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Surgery; Thromboplastin - metabolism; Treatment Outcome; Tumor proteins; Tumor Suppressor Protein p53 - genetics; Tumors; Tissue factor; Colorectal cancer; Human; Rectal disease; Prognosis; Colorectal carcinoma; p53 Protein; Malignant tumor; p53; Colonic disease; K-ras; Gastroenterology; Digestive diseases; Intestinal disease; Mutation; Onc gene; Cancer
• ISSN: 0179-1958; 1432-1262
• DOI: 10.1007/s00384-011-1164-1

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.