The Relationship Of FHIT, C-Met With PCNA And Their Clinical Significance In Colorectal Carcinoma.

Colorectal carcinoma is one of the most common digestive carcinoma ,its mortality only inferior to gastric carcinoma, esophageal carcinoma and lung carcinoma ,ranking the forth in our country .Recently, mortality of colorectal carcinoma has been increasing, but its mechanism has not been cleared. Thus, recent studies pay attention to the etiology and morbidity of colorectal carcinoma. Fragile histidine triad ( FHIT) gene, discovered as a new tumor candidate suppress gene ,lied in chromosome 3p14.2 Fragile site spanning 3 chromosome Fragile region FRA3B,where there was the region of rearrangement of chromosome which easily caused LOH and methylamine of the 5'CPG island of FHIT gene.The protein, FHIT produced, similaring to Ap4A unsymmetrical hydrolase , played important roles in cell growth and controled the growth inhibitory signal, which induced cell apoptosis and inhibit carcinoma cell proliferation in vitro.Proliferation cell nuclear antigen (PCNA)was an essential protein for cell-cycle regulation correlating with the growth potential. Its positive expression showed that cell was nuclear proliferation .c-Met was the receptor of HGF(Hepatocyte growth factor) . HGF played on c-Met so that c-Met was reverse phosphorylation. The latterinduced happenning .development and metastasis and cell proliferation of carcinoma through autocrineand paracrine .Recent studies showed that FHIT and c-Met related to happenning and development of carcinoma . In addition, they have been believed as the prognosis markers of carcinoma. But they had less been studied in colorectal carcinoma .In order to evaluate the roles of FHI and c-Met in colorectal carcinoma and the prognosis of them as well as their interaction, immunohistochemical technique was applied in examining the expression of c-Met, FHIT and PCNA.lt was expected that the study will help us to judge the prognosis and therapy of colorectal carcinoma.Materials and Methods: (1)60 cases colorectal carcinoma and 24 casescolorectal adenoma surgically resected and fibrocoloroscopy biopsy samples were collected . 24 cases normal mucosa samples which were adjacent to carcinoma mucosa were confirmed pathologically. All tissues were fixed in 10% neutral formalin and embedding in paraffin . (2) Sp immunohistochemtry was used to examine the expression of FHIT, c-Met and PCNA in colorectal carcinoma, adenoma andnormal mucosa. (3) The data was analysized by software SPSS10.0 ,x2 -test, testexact probabilities in 2x2 table and spearman correlation were used to evaluate the statistical significance.Results: (1) FHIT was stained mainly in the cytoplasm of normal mucosa andepithelial cells of carcinoma ,and occasionally evidence in some interstitial cells, such as lymphocyte, plasmocyte, ect. FHIT stained in normal mucosa, adenoma and carcinoma of colorectal showed decreasing, the rates of expression were 56.3%, 25%and 35%,respectirely.There was significant differences ( P<0.05) in above three groups.There was no significant differences in adenoma and carcinoma (P>0.05). c-Met was equal to that of FHIT. Normal epithetical cells were homogeneously stained whereas the positive tumor cells were hetergene only distributed within colorectal carcinoma .The expression rate of c-Met in normal mucosa, adenoma and colorectal carcinoma were 8.3%, 35%and 63.3%,respectively.There was significant differences in above three groups(P<0.05)when comparison was made. PCNA was stained mainly in nuclear. Its expression in normal mucosa, adenoma and colorectal carcinoma were all sufficient positive. The rates of expression were 16%, 50%and80%, there was significant differences (P<0.05). (2) According to the degree of differentiation of colorectal carcinoma, 60 samples were divided into two groups including better grades and poorer grades. In the two groups, the positive expression rates of c-Met were 37.5%and 75%, respectively. Comparison between the above two groups was significant differences (P<0.05). The positive expression of FHIT was 45%and 80%, respectively. There was...