Expression Of Maspin, UPA And B-FGF In Colon Cancers And Its Clinical Significance

Background and ObjectivesColon Cancer is one of the most common gastroenteric malignant diseases. the incidence and mortality of colon cancer displays ascending tendency year by year. Invasion and metastasis of colon cancer is the most important reason of curative failure and the patients' death. Increasing invasion capacity of tumor cells and angiogenesis play the key roles in the tumor progress.Maspin protein belongs to serine protease inhibitor superfamily and has been identified as a tumor suppressor. The expression of maspin is detected in epithelium cells of many normal human organs; however, the corresponding tumor cells show decreased expression or an absence of expression. Maspin has been demonstrated as an effective inhibitor of angiogenesis. Several studies support the hypothesis that maspin functions at the level of invasion and metastasis by blocking tumor cell migration and proliferation.Urokinase type plasminogen activator (uPA) is one kind of serine protease which produced by endoplasmic reticulum. Plasminogen would come to the active type, when uPA combines to the specific receptor. That would be benefit for the invasion and metastasis of tumor cell.There is little basic-fibroblast growth factor (b-FGF) consist in normal tissues. The increasing of b-FGF in tumor cells could promote angiogenesis that could provide nourishment and oxygen to the tumor.In this study, we try to determine the expression of maspin protein, uPA protein and b-FGF protein in colon cancers and analyze the relationship between the expression and the behavior of colon cancer.Materials and Methods(1) Ninety-nine samples which were obtained from the Pathology Department of the First Affiliated Hospital of Zhengzhou University between 2003-2004 were included in the study. There were 50 colonic adenocarcinomas, 24 colonic adenomas and 25 normal colon samples of the 99 samples. None of the patients had received chemotherapy or radiation therapy before surgery.(2) The expression of maspin protein, uPA protein and b-FGF protein in normal epithelium, adenoma and adenocarcinoma of colon were examined by use of S-P immunhistochemistry.(3) The data was analyzed by software SPSS 10.0. x~2-test and spearman correlation were used to analyze the difference between groups,α=0.05 was considered as statistically significant value.Results(1) Twenty-three (92.00%) of the 25 normal colonic epithelium were positive, whereas 20 (83.33%) of the 24 colonic adenomas were positive for maspin. Only 24 (48.00%) of the 50 colonic adenocarcinomas showed a positive maspin expression. There were statistically significant differences among the three groups (P < 0.05). The percentage of samples positive for maspin protein in colonic adenocarcinoma cells was correlated to depth of invasion, lymph nodes metastasis, histological grade and Dukes stage (P < 0.05). There was significant difference of the positive expression rate of maspin protein between the serosal infiltration group 25.93%(7/27) and the subserosa group 73.91 %(17/23) (P < 0.05). There exited significant difference of the positive expression rate of maspin protein between the lymph node metastasis positive group 23.81 %(5/21) and the lymph node metastasis negative group 65.52%(19/29) (P < 0.05). There was significant difference of the positive expression rate of maspin protein between the higher 61.29%(19/31) and lower histological grade 26.32%(5/19) (P < 0.05). There was a higher positive expression rate of maspin protein in the A+B group 72.22%(13/18) than that in the C+D group 34.38%(11/32) (P < 0.05).(2) Only one (4.00%) of the 25 normal colonic epithelium showed a positive uPA expression. Eight (33.33%) of the 24 colonic adenomas were positive, whereas 38 (76.00%) of the 50 colonic adenocarcinomas were positive for uPA. There were statistically significant differences among the three groups (P < 0.05). The percentage of samples positive for uPA protein in colonic adenocarcinoma cells was correlated to depth of invasion, lymph nodes metastasis, histological grade and Dukes stage (P < 0.05). There was significant difference of the positive expression rate of uPA protein between the serosal infiltration group 92.59%(25/27) and the subserosa group 56.52%(13/23) (P < 0.05). There exited significant difference of the positive expression rate of uPA protein between the lymph node metastasis positive group 95.24%(20/21) and the lymph node metastasis negative group 62.07%(18/29) (P< 0.05). There was significant difference of the positive expression rate of uPA protein between the higher 64.52%(20/31) and lower histological grade 94.74%(18/19) (P< 0.05). There was a lower positive expression rate of uPA protein in the A+B group 50.00%(9/18) than that in the C+D group 90.63%(29/32) (P < 0.05).(3) Only two (8.00%) of the 25 normal colonic epithelium showed a positive b-FGF expression. Six (25.00%) of the 24 colonic adenomas were positive, whereas 34 (68.00%) of the 50 colonic adenocarcinomas were positive for b-FGF. There were statistically significant differences among the three groups (P < 0.05). The percentage of samples positive for b-FGF protein in colonic adenocarcinoma cells was correlated to depth of invasion, lymph nodes metastasis and Dukes stage (P < 0.05). There was significant difference of the positive expression rate of b-FGF protein between the serosal infiltration group 81.48%(22/27) and the subserosa group 52.17%(12/23) (P < 0.05). There exited significant difference of the positive expression rate of b-FGF protein between the lymph node metastasis positive group 85.71%(18/21) and the lymph node metastasis negative group 55.17%(16/29) (P < 0.05). There was a lower positive expression rate of uPA protein in the A+B group 50.00%(9/18) than that in the C+D group 78.13%(25/32) (P < 0.05). There was no significant difference of the positive expression rate of uPA protein between the higher 58.06%(18/31) and lower histological grade 84.21%(16/19) (P > 0.05).(4) In the 50 colonic adenocarcinomas, 14 (28%) showed positive maspin protein and uPA protein expression at the same time while 2 (4%) showed negative maspin protein and uPA protein expression. There was negative correlation between the expression of maspin protein and uPA protein (P < 0.05). Ten (20%) of the 50 colonic adenocarcinomas showed positive maspin protein and b-FGF protein at the same time while 3 (6%) of the 50 showed negative maspin protein and b-FGF protein expression. There was negative correlation between the expression of them (P < 0.05). Thirty (60%) of the 50 colonic adenocarcinomas were positive for uPA protein and b-FGF protein at the same time while 6 (12%) of the 50 were negative. There was positive correclation between the expression of uPA protein and b-FGF protein (P < 0.05).Conclusions(1) The positive rate of maspin protein in adenoma is lower than normal colonic epithelium while the positive rate of uPA protein and b-FGF protein in adenoma is higher, which indicate the down-regulating of maspin and the up-regulating of uPA and b-FGF play important role in the origin of colonic adenoma.(2) We demonstrate maspin protein expression in colon cancer with a sequential decreased expression rate from normal colonic epithelium, adenoma to adenocarcinomas, which signifies the tumor suppressive function of maspin.(3) uPA protein and b-FGF protein expression in colon cancer with a sequential increased expression rate From normal colonic epithelium, adenoma to adenocarcinomas, which signifies the tumor promote function of uPA and b-FGF.(4) There is decreased expression rate in colonic adenocarcinomas. The inverse correlation of the up-regulating of uPA and b-FGF indicates them three interact each other and have effects on tumor progressing.(5) The combined examination of maspin, uPA and b-FGF expression may aid in forepart diagnosis and forecasting the course of colon cancers.