MDM2 mRNA expression in the p53 pathway may predict the potential of invasion and liver metastasis in colorectal cancer.
OBJECTIVE
The p53/MDM2/p14ARF pathway is one of the major signaling cascades involved in the regulation of apoptosis. Although many tumors have been reported to show disruption of the p53/MDM2/p14ARF pathway, few studies have examined p53, MDM2, and p14ARF simultaneously in colorectal carcinoma. The present study was undertaken to clarify whether correlations exist among MDM2, p53, and p14ARF in colorectal cancer.


METHODS
We determined the presence of mutations in the p53 gene, MDM2 expression, and methylation status of the p14ARF in 97 primary colorectal carcinoma specimens. Associations with survival and clinicopathologic factors were investigated.


RESULTS
At least one abnormality of these three molecules was found in 82 (84 percent) tumors. We observed a significant inverse association between MDM2 expression and tumor invasion (P = 0.01). Furthermore, the presence of liver metastasis was also significantly associated with low MDM2 expression (P = 0.02).


CONCLUSIONS
The results suggest that disruption of the p53/MDM2/p14ARF pathway may frequently participate in colonic carcinogenesis and that MDM2 expression status may be a factor in the prediction of potential invasion and liver metastasis of colorectal carcinomas.
Kondo
Ito
I
Department of Surgical Oncology, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, Tokyo, Japan. ito-k@pop21.odn.ne.jp
Iida
Satoru
S
Takagi
Yoko
Y
Sugihara
Kenichi
K
D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology*; D019175:DNA Methylation; D005260:Female; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000401:mortality / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D025803:Tumor Suppressor Protein p14ARF; D051736:Proto-Oncogene Proteins c-mdm2