Expression And Significance Of Ets-1 And Its Related Factors In Tissue Microarray Of Colorectal Carcinoma

OBJECTIVE: To investigate the expression of Ets-1 and its related factors VEGF, MMP-9 in colorectal tumor, and study the function of Ets-1 in colorectal carcinogenesis, invasion and metastasis; Also to explore the possible mechanism of Ets-1, VEGF and MMP-9 in invasion and metastasis in colorectal carcinoma.METHODS: Using tissue microarray technique and immunohistochemical SP staining method, the expression of Ets-1, VEGF and MMP-9 were detected in 51 colorectal adenocarcinoma, 27 adenoma, 15 hyperplastic polyp, 14 normal tissue and 15 adjacent no-tumor tissue respectively, and the statistic method was exert to analyzed the expression of Ets-1 correlated with the expression of VEGF and MMP-9, as well as the relationship of clinicopathological parameters.RESULTS: (1) The frequency of positive expression of Ets-1 protein in colorectal carcinoma was 70.6% and showed higher significantly than in normal colorectal tissues (21.4%), adjacent no-tumor tissue (35.7%), colorectal adenoma (37%) and colorectal polyp (20.0%) (P< 0.05).(2) In colorectal adenoma, Ets-1 protein expressed mainly in atypical hyperplasia cells. The group with moderate-severe atypical hyperplasia was higher significantly than the group with mild-moderate atypical hyperplasia (the frequency of positive expression was 23.1% and 64.3% respectively) (P<0.05), but the group with moderate-severe atypical hyperplasia was no statistic significance with colorectal carcinoma (P>0.05); And the various histological type groups were no statistic significance (P>0.05).(3) The expression level of Ets-1 with lymph node metastasis (93.8%) was higher significantly than that with no lymph node metastasis (60.0%) in colorectal carcinoma (P< 0.05); The deeper of the tumor invasion,the higher of Ets-1 expression, and showed statistic significance (P<0.05); Significant difference was found between Dukes stage A/B and C/D group (P<0.05). However, the Ets-1 protein expression level did not relate to age, sex, pathologic grade and histological type (P>0.05).(4) The frequency of positive expression of MMP-9 protein in colorectal carcinoma was 62.7%, and higher significantly than that in adjacent no-tumor tissue, normal colorectal tissue, colorectal adenoma and colorectal polyp (P<0.05); The expression level of MMP-9 was up-regulated gradually with the depth of invasion increased, and showed statistic significance (P<0.05); Significant difference was found between Dukes stage A/B and C/D group (P< 0.05); The expression level of MMP-9 with lymph node metastasis was significantly higher than that with no lymph node metastasis in colorectal carcinoma (P<0.05).(5) The frequency of positive expression of VEGF protein in colorectal carcinoma was 68.6%, and it was higher significantly than that in adjacent no-tumor tissue, normal colorectal tissue, colorectal adenoma and colorectal polyp (P<0.05); The expression level of VEGF was gradually up-regulated with the depth of invasion increased and Dukes stage increased, both showed statistic significance (P<0.05); Significant difference was found between the group with lymph node metastasis and the group with no lymph node metastasis in colorectal carcinoma (P<0.05).(6) The expression of Ets-1 positively associated with that of MMP-9 (P<0.05); The expression of Ets-1 positively associated with that of VEGF (P<0.05).CONCLUSIONS: (1) Ets-1 takes part in the process of malignant change of colorectal adenoma. The increased Ets-1 implies that it maybe play an important role in the colorectal carcinogenesis and inducement malignant cell. There is the possibility that Ets-1 act as a marker of the adenoma cancerization.(2) The frequency of positive expression of Ets-1 protein in colorectal carcinoma is higher, and which correlates with invasiveness and metastasis in colorectal carcinoma.(3) VEGF and MMP-9 are over-expression in colorectal carcinoma and correlate with invasiveness and metastasis in colorectal carcinoma.(4) Ets-1 promotes invasiveness and metastasis in colorectal carcinoma by controlling the expression of VEGF and MMP-9. The expression of Ets-1,VEGF and MMP-9 maybe one of important indicator for determining malignant biological behavior in colorectal carcinoma, and they also give some messages about prognosis.(5) Tissue microarray technique has the advantage of high-throughput in the detection of colorectal tumor related genes, which can analyze amounts of specimens and costless working time, and it is a valuable technique in pathology research.