Expression Of Ezrin, Mmp-9 And Mvd In Gastric Carcinoma And Its Significance

Gastric carcinoma is a common malignant tumor of digestive system. In china, the morbidity of gastric carcinoma takes the first in various types of cancer. As a result of early Gastric carcinoma usually without specific symptoms, its early detection is very difficult, and because of Gastric carcinoma prone to metastasis by lymph and blood, its prognosis is extremely poor and 5-year survival rate is very low. Metastasis is a complex pathological process which is regulated by the gene, involved multi factors and developed with multi-stage. The existing research results show that this process is regulated by variety of factors such as tumor metastasis genes and metastasis suppressor gene, angiogenesis factors and lymphangiogenic factors, polysaccharides, adhesion molecules, extracellular matrix.Ezrin is a membrane cytoskeleton cross linker protein which has the functions such as retain the cell morphology and movement, connect with adhesion molecules, and regulate signal transduction. A large number of research results have showed that the expression level of Ezrin protein in many tumor tissues was significantly higher than normal tissue. Ezrin protein was over-expression in the tumor cells that have the ability of metastasis, and often changed in subcellular localization in the tumor cells Ezrin protein mainly through regulating cell adhesion, signal transduction, apoptosis and phagocytosis of tumor cells to participate in all aspects of tumor metastasis and affect the infiltration and metastasis of tumors. Matrix metalloproteinases (matrix metalloproteinases, MMPs) are a family of zinc dependent enzymes whose primary role is to degrade extracellular matrix, such as collagenase, gelatinases, and stromelysins. As one important member of the family, MMP-9 can degrade and destroy surface collagen and gelatin and result in infiltration and metastasis of tumor cells through damaged basement membrane to surrounding tissue.Tumor's growth and metastasis depend on angiogenesis. Angiogenesis is the basis for tumor growth, invasion, metastasis and recurrence. Abundant vessels not only increase the invasive tumor cells' chances of entering the blood circulation, and also promote lymphatic metastasis. Micro vessel density (micro vessel density, MVD) can show the proliferation of tumor angiogenesis and estimate the tumor's metastatic potential.It has not been reported that the expression of Ezrin and MMP-9 in gastric cancer and its relationship with MVD so far at home and abroad. In order to discuss the mechanisms of infiltration and metastasis of gastric carcinoma and search valid methods which can suppress the infiltration and metastasis of gastric carcinoma, this research adopts immunohistochemistry SP method to observe the expression of Ezrin, MMP-9 and MVD in 52 cases of gastric carcinoma tissues, 31 cases of non-atypical hyperplasia tissues and 21 cases of normal mucosa tissues.Methods1. Using the immunohistochemistry SP technology to detect the expression of Ezrin,MMP-9 and MVD in the 52 cases of gastric carcinoma, 31 cases of atypical hyperplasia tissues and 21 cases of normal mucosa of gastric carcinoma respectively.2. Statistical analysis: All the data were analyzed by SPSS 10.0 statistical package. The Chi-square was used in the comparison of positive rates; the t-test was used in the comparison of means between two groups; the One-Way ANOVA was used in the comparison of means between three groups; the relation of two variables was analyzed by the spearman level correlation analysis. The level of significant difference wasα=0.05. Results1. The positive expression rates of Ezrin protein in normal mucosa of stomach, atypical hyperplasia tissues, and carcinoma tissues were 4.8% (1/21), 35.5% (11/31) and 63.5%(33 /52) respectively; the positive expression rate of Ezrin protein in the carcinoma tissues was compared with that in the atypical hyperplasia tissues and normal mucosa tissues from each other, and there was statistical significance (P <0.01).2. In the tissues of gastric carcinoma, the positive rates of expression of Ezrin protein on the low-muscle invaded, deep-muscle invaded and outer layer invaded were 44.4% (8/18), 52.9% (9/17) and 94.1% (16/17) respectively. The expression of Ezrin in the carcinoma tissues with the outer layer invaded was evidently higher than that in the tissue with low-muscle invaded and deep-muscle invaded. There was significant difference among the groups (P<0.01). Thus the expression of Ezrin in the carcinoma tissues with deep-muscle was compared with that with low-muscle, and there was no significance (P>0.05).3. In the 32 cases of metastatic group, the positive rate of expression of Ezrin protein in the tumor tissues was 81.3% (26/32); in the non-metastatic group, it was 35.0% (7/20). There was significant difference between the two groups (P<0.01).4. The positive expression rates of MMP-9 protein in normal mucosa of stomach , atypical hyperplasia tissues, and carcinoma tissues were 14.30% (3/21), 48.40% (15/31) and 75.00% (39/52) respectively; the positive expression rate of MMP-9 protein in the carcinoma tissues was compared with that in the atypical hyperplasia tissues and normal mucosa tissues from each other, and there was statistical significance(P<0.016).5. In the tissues of gastric carcinoma, the positive rates of expression of MMP-9 protein on the low-muscle invaded, deep-muscle invaded and outer layer invaded were 44.4% (8/18),58.8% (10/17) and 94.1% (16/17) respectively. The expression of MMP-9 in the carcinoma tissues with the outer layer invaded was evidently higher than that in the tissue with low-muscle invaded and deep-muscle invaded. There was significant difference among the groups (P<0.05). Thus the expression of MMP-9 in the carcinoma tissues with deep-muscle was compared with that with low-muscle, and there was no significance (P>0.05).6. In the 32 cases of metastatic group, the positive rate of expression of MMP-9 protein in the tumor tissues was 81.3% (26/32); in the non-metastatic group, it was 40.00% (8/20). There was significant difference between the two groups (P<0.01).7. The means of MVD in normal mucosa of stomach, atypical hyperplasia tissues and carcinoma tissues were 18.10±8.37,35.77±7.82 and 43.60±8.73 respectively, the means of MVD in the carcinoma tissues was compared with that in the atypical hyperplasia tissues and normal mucosa tissues from each other, and there was statistical significance(P<0.01).8. In the tissues of gastric carcinoma, the means of MVD in the low-muscle invaded, deep-muscle invaded and outer layer invaded were 35. 89±6. 07,43.18±6. 91 and 52. 18±3. 28 respectively. The mean of MVD in the carcinoma tissues with the outer layer invaded was evidently higher than that in the tissue with low-muscle invaded and deep-muscle invaded. There was significant difference among the groups (P<0.001).9. In the 32 cases of metastatic group, the mean of MVD in the tumor tissues was 48.53±6.01; in the non-metastatic group, it was 48.53±6.01. There was significant difference between the two groups (P<0.001).10. The relativity of the expression of Ezrin and MMP-9 in gastric carcinoma was analyzed statistically. Results showed that the expression of Ezrin was positively correlated with that of MMP-9(P<0.01); the mean of MVD in the carcinoma tissues with the positive expression of Ezrin protein(47.52±7.72) was evidently higher than that in the tissue with the negative expression of Ezrin protein (36.79±5.74) . There was significant difference among the groups (P<0.001). The mean of MVD in the carcinoma tissues with the positive expression of MMP-9 protein (47.62±7.35) was evidently higher than that in the tissue with the negative expression of MMP-9 protein(36.00±5.51) . There was significant difference among the groups (P<0.001). Conclusions1. Ezrin participates in occurrence and development of gastric carcinoma and also in infiltration and metastasis of gastric carcinoma.2. MMP-9 participates in occurrence and development of gastric carcinoma and also in infiltration and metastasis of gastric carcinoma.3. Micro vessel proliferation participates in occurrence and development of gastric carcinoma. Also Micro vessel proliferation participates in infiltration and metastasis of gastric carcinoma.4. Ezrin, MMP-9 and the Micro vessel may play a synergistic effect during the process of occurrence and development and infiltration, metastasis of gastric carcinoma.