The Role Of Wnt Signaling Pathway In Pathogenesy Of Scirrhous Gastric Carcinoma

Background and Objective:Gastric carcinoma, whose morbidity and mortality takes the first place, is one of the most seen digestive malignant tumors in our country. Scirrhous gastric carcinoma, also called widespread and invasive gastric cancer, Borrmann typeⅣgastric cancer, is one of gastric cancers with peculiar biological feature. The carcinoma grows diffusively and invasively in all layers of stomach with marked stromal fibrosis, it is high in malignancy, early in lymph-node metastasis, fast in progress and poor in prognosis. The genesis of gastric carcinoma is a complicated course with multifactor, multistage and multigene mutation accumulation. It is complex in mechanism of molecular biology. Recently, the study of tumor genesis and development mechanism is focused on cloning and functional analysis of tumor-related gene, cell signaling and control of cell cycle. Wnt signaling pathway is a signaling system which has important regulating effect on cell proliferation and differentiation, more and more researches proved that beside regulating development process, abnormal activation or space-time expression of Wnt signaling pathway will result in manligant transformation of cells and tumor genesis. As a result, we will obtain further understanding of tumor genesis and development if we carry out more profound study of Wnt signaling pathway.This study is trying to find relationship between Wnt signaling pathway and scirrhous gastric carcinoma through detection the expression of Wnt2,β-catenin, CTGF and typeⅠandⅢcollagen fibers in scirrhous gastric carcinoma(SC group), non-scirrhous gastric carcinoma(NSC group) and normal stomach tissue(control group).Materials and methods:58 cases of gastric carcinoma surgical samples were collected in the first affiliated hospital of Dalian medical university from 2001 to 2008, SP immunohistochemistry (IHC) staining was used to observe the expression of CTGF in 29 cases of SC group, 29 cases of NSC group and 30 cases of control group. Two-step IHC staining was performed to assess the expression of Wnt2 andβ-catenin in the groups mentioned above. Sirius-red staining was applied to detect the expression of typeⅠandⅢcollagen fibers. SPSS13.0 was used to analyze the data obtained in the experiment.Results:1. The expression of Wnt2 in gastric carcinoma groups was significantly higher than that in the control group(P<0.01), while there was no difference between scirrhous gastric carcinoma(SC) and non-scirrhous gastric carcinoma(NSC)(P> 0.05). The expression of Wnt2 was correlated with pathologic classification, but not with invasion depth, lymphatic metastasis, clinical stage, age and sex(P> 0.05).2. There was significant difference ofβ-catenin expression in cell membrane, cytoplasma and nuclear among SC group, NSC group and control group(P<0.01). The expression ofβ-catenin decreased on cell membrane of carcinoma tissue while increased in cytoplasma and nuclear. There were significant difference between different groups and different locations(P<0.01) except the expression on cell membrane and cytoplasma between SC and NSC groups(P> 0.05). The abnormal expression ofβ-catenin in cell membrane, cytoplasma and nuclear were not correlated with invasion depth, clinical stage, lymphatic metastasis, pathologic classification( P>0.05 ) except the relation between nuclear expression and pathologic classification(P<0.01). The expression ofβ-catenin in different location is not correlated with age and sex(P> 0.05).3. The expression of CTGF and typeⅠandⅢcollagen fibers in SC and NSC groups were obviously higher than that in control group(P<0.01), and expression in SC group was higher than NSC group(P<0.01). The abnorml expression of CTGF and typeⅠandⅢcollagen fibers was correlated with invasion depth, clinical stage, lymphatic metastasis and pathologic classification(P<0.01) but not correlated with age and sex(P> 0.05).4. The correlation analysis. The expression of Wnt2 was positively correlated with CTGF and typeⅠandⅢcollagen fibers and cytoplasma and nuclear expression ofβ-catenin, while negatively correlated with cell membrane expression ofβ-catenin(P<0.01). The expression of CTGF was positively correlated with typeⅠandⅢcollagen fibers and cytoplasma and nuclear expression ofβ-catenin, while negatively correlated with cell membrane expression ofβ-catenin(P<0.01). The expression of typeⅠandⅢcollagen fibers was positively correlated with cytoplasma and nuclear expression ofβ-catenin but negatively correlated with cell membrane expression ofβ-catenin(P<0.01).Conclusion:1. The expression of Wnt2 in gastric carcinoma groups was significantly higher than that in control group, and there was obvious difference ofβ-catenin between gastric carcinoma groups and control group, it suggests that Wnt/β-catenin signaling pathway is activated in gastric carcinoma.2. The abnormal expression ofβ-catenin in SC group was obviously higher than that in NSC group and control group, it indicates that the activation of Wnt/β-catenin signaling pathway may have close relationship with formation of scirrhous gastric carcinoma.3. The expression of CTGF and typeⅠandⅢcollagen fibers was significantly increased in scirrhous gastric carcinoma, and positively correlated with Wnt2 expression, cytoplasma and nuclear expression ofβ-catenin, it implies that CTGF may play an important role in pathogenesis of scirrhous gastric carcinoma through Wnt signaling pathway.