Methylation of p14ARF and abnormal expression of p53 and mdm2 in colorectal cancer: Role and correlation

Methylation of p14ARF in 42 samples of colorectal cancer and matched adjacent normal tissues was evaluated by methylation-specific PCR (MSP) method. Expressions of p53 and mdm2 were detected by using the semi-quantitative RT-PCR. Protein expressions of p14ARF, p53 and mdm2 in the two groups were assessed with immunohistochemical staining. Research data were analyzed with Student's t-test, chi-square test and Spearman rank correlation. p14ARF methylation was identified in 19 (45.2%) of 42 samples of colorectal cancer tissues and none of the 42 (0%) samples had normal adjacent tissues, indicating a statistically significant difference between the two groups (p <0.05). Positive protein expression rates of p14ARF, p53 and mdm2 in 42 samples of colorectal cancer tissues were 16.7, 73.8 and 54.5%, respectively, while they were 95.2, 11.9 and 28.6% in normal adjacent tissues. A statistically significant difference was noted between the two groups (p <0.05) regarding protein expression of three genes. Protein expressions of mdm2 and p53 were positively correlated (r = 0.423; p <0.05) and protein expression of both was negatively correlated with p14ARF protein expression. p14ARF methylation or protein expressions of p53 plus mdm2 were not correlated with the age, sex or tumor size in patients with colorectal cancer, but were positively correlated with tumor differentiation and lymph node metastasis. p14ARF methylation is closely correlated with colorectal cancer and may be an early event in its occurrence; however, p14ARF methylation and abnormal expression of mdm2 plus p53 play a major role in the occurrence and development of colorectal cancer. As the p53-dependent pathway is one of the major regulation channels for growth of colorectal epithelial cells, simultaneous assessment of p14ARF methylation and abnormal expression of MDM2 plus p53 may work as a biological indicator for early diagnosis of colorectal cancer.