Expression And Significance Of MTA1,nm23-H1 And E-cad In Esophageal Squamous Carcinoma

In rencent years, cloning many variety of genes which is relative to infiltration metastasis of tumor one after another, among the total MTA1, Metastasis-Associated gene 1 that was discovered, is a relative gene of tumor metastasis, which is relative to signal conduction and gene regulation. The research confirmed that MTA1 protein contains some structures of gene regulatory protein and linking protein, thus in the process of infiltration and metastasis of tumor, MTA1 gene product plays important roles in the signal conduction. At present a lot of researchs indicates that MTA1 is relative to infiltration and metastasis of tumor closely. nm23-H1,non-metastatic gene 23-H1 is a kind of tumor metastasis phenotypic suppression gene, which encodes nucleoside diphosphate kinase of generating nucleoside triphosphate, Inactivation of a subunit leads to proportional disequilibrium of NDPK and shortage of NTP, thus affecting microtubule polymerizing and resulting in disintegration of chromatosome and formation of anorthoploid, promoting the metastasis of tumor. Investigations indicate that nm23-H1 gene suppress cellular reaction of platelet-derived growth factor insulin-like growth factor-I and affect cellular mobility, thereby suppressing the process of metastasis of tumor. The research confirmed that nm23-H1 gene generates mutation depletion and expression lower in many kinds of high potentiality of metastasis of tumor, indicating that nm23-H1 is relative to metastatic potentiality of malignant tumor closely. E-cad,E-cad belongs to one of transmembrane protein of cellular adhesion molecule family, which is located in endothelial cell and whose positive expressions suppresses the metastasis of tumor. Expression lower or deletion of E-cad leads to the ablity of cellular adhesion from each other and results in scattering of tumor cells easily and infiltrating and growing toward surroundings, thus breaking away from primary place and infiltrating and metastasis. The research discoved that the down regulation or deletion of expression of E-cad is important malignant biological behavior of tumor, suggesting expression level of E-cad may be regarded as one of indexes of metastatic ability of malignant tumor.China has the first morbidity and mortality of eophageal carcinoma in the world, Morbidity and mortality of eophageal carcinoma of Henan province are both the first, but Therefor exploring the mechanism of the invasion and metastasis of esophageal carcinoma has been one of research hot spots. How MTA1 nm23-H1 and E-cad and its relationship with the invasion and metastasis of esophageal carcinoma as well as mutual relationships among them researchs, to this date domestic and foreign documents have not reports. In order to discuss the mechanisms of esophageal carcinoma , seach valid methods, which can suppress the infiltration and metastasis of esophageal carcinoma and extend survival time of esophageal carcinoma patients cut downmortality rate. Our research adopts immunohistochemistry sp method, observing the expressions of MTA1 nm23-H1 and E-cad protein in esophageal carcinoma tissues of 49 cases adjacent non-atypical hyperplasia tissues of 30 cases and normal mucosa tissues of 49cases, Detecing unitedly illuminates furtherly the mechanisms of infiltration and metastasis of esophageal carcinoma and provides theoretical foundation for blocking invasion and metastasis of esophageal carcinoma.MaterialsThe tissue samples were procured in the Henan Anyang Cancer Hospital and the First Hospital of Zhengzhou University from Sep 2004 to Nov 2004. Samples of cancerous tissue, adjacent tissues to the carcinoma and the normal tissue were resected in 49 cases of esophageal squamous carcinoma. We took the 49 cancerous tissues, 30 atypical hyperplasia tissues adjacent to the carcinoma and 49 normal esophagus mucosa epithelial tissues as investigative objects. The 49 cancerous samples were sorted into metastatic group (20 cases) and non-metastatic group (29 cases) according to lymphonode involvement, and also sorted into low-muscle invaded group (10 cases), deep-muscle invaded group (15 cases) and outer lay group (24 cases) according to mucous membrane infiltrated depth. The samples were sorted into esophagus carcinoma group (49 cases), atypical hyperplasia group (30 cases) and normal esophagus mucosa epithelial group (49 cases) according to cancer occurrence and development. All the samples were treated by 10% formalin fixation, paraffin imbedding and serial sectionsof 4μm thick, and then detected by immunohistochemistry.Methods1. Using the technology of immunohistochemistry SP to detect the expression of MTAl nm23-H1 and E-cad in the 49 cases of esophageal squamous cell carcinoma, 30 cases of atypical hyperplasia tissues of tumor-adjacent and 49 cases of normal mucosa of esophageal carcinoma respectively .2. Statistical analysis: All the dates were analyzed by SPSS 11.0 statistical package, the count information calculated the positive rate, The comparison of positive rates uses the Chi-square ;The relation of two variable are analyzed by the spearman level correlation analysis.The level of significant difference is a=0.05.Results1. Immunohistochemical results indicated: the positive expression rate of MTA1 protein in normal mucosa of esophagus is 0%(0/49); The positive expression rate of MTA1 protein in atypical non-hyperplasia tissues is 26.67% (8/30) ; The positive expression rate of MTA1 protein in the carcinoma tissues is 63.27%(31/49), the positive expression rate of MTA1 protein in the carcinoma tissues is compared with that in the propotional adjacent tissues and normal mucosa tissues from each other, there is statistital significance( P <0.05).2. Immunohistochemical results indicated: the positive expression rate of nm23-H1 protein in normal mucosa of esophagus is 100%(49/49); The positive expression rate of nm23-H1 protein in atypical non-hyperplasia tissues is 66.67% (20/30) ; The positive expression rate of nm23-H1 protein in the carcinoma tissues is 46.93%(23/49) the positive expression rate of nm23-H1 protein in the carcinoma tissues is compared with that in the propotional adjacent tissues and normal mucosa tissues from each other, there is statistital significance( P <0.05).3. Immunohistochemical results indicated: the positive expression rate of E-cad protein in the carcinoma tissues, atypical non-hyperplasia tissues and normal mucosa of esophagus is 46.89%(22/49) , 70%(21/30) and 100%(49/49) respectively, the positive expression rate of E-cad protein in the carcinoma tissues is compared with that in the propotional adjacent tissues and normal mucosa tissues from each other, there is statistital significance( P <0.05) .4. In the 20 cases of metastatic group, the positive rates of expression of MTA1 protein in the tumor tissues are 80%( 16/20); in the non-metastatic group, they are 51.72% (15/29). There is a significant difference between the two groups (P<0.05).5. In the 20 cases of metastatic group, the positive rates of expression of nm23-H1 protein in the tumor tissues are 30%(6/20); in the non-metastatic group, they are 58.62% (17/29). There is a significant difference between the two groups (P<0.05).6. In the 20 cases of metastatic group, the positive rates of expression of E-cad protein in the tumor tissues are 25%(5/20); in the non-metastatic group, they are 58.62% (17/29). There is a significant difference between the two groups (P<0.05).7. In the tissues of esophageal squamous cell carcinoma,the positive ratio of expression of MTA1 protein on the low-muscle invaded, deep-muscle invaded and outer lay invaded is 40% (4/10), 46.67% (7/15) and 83.33% (20/24) respectively. The expression of MTA1 in the carcinoma tissues with the outer lay invaded is higher than that in the tissue with low-muscle invaded and deep-muscle invaded. There was a significant difference among the groups. (P<0.05). Thus the expression of MTA1 in the carcinoma tissues with deep-muscle is compared with that with low-muscle, there is no significance (P>0.05).8. In the tissues of esophageal squamous cell carcinoma,the positive radio of expression of nm23-H1 protein on the low-muscle invaded, deep-muscle invaded and outer lay invaded is80% (8/10), 40.00% (6/15) and 37.50% (9/24) respectively. The expression of nm23-H1 in the carcinoma tissues with low-muscle invaded is higher than that in the tissue with outer lay invaded and deep-muscle invaded. There was a significant difference among the groups. (P<0.05). Thus the expression of nm23-H1 in the carcinoma tissues with deep-muscle is compared with that with outer lay, there is no significance (P>0.05).9. In the tissues of esophageal squamous cell carcinoma,the positive radio of expression of E-cad protein on the low-muscle invaded, deep-muscle invaded and outer lay invaded is 90% (9/10), 46.67% (7/15) and 25% (6/24) respectively. The expression of E-cad in the carcinoma tissues with low-muscle invaded is higher than that in the tissue with outer lay invaded and deep-muscle invaded. There was a significant difference among the groups. (P<0.05). Thus the expression of E-cad in the carcinoma tissues with deep-muscle is compared with that with outer lay, there is no significance (P>0.05).10. The relativity of the expression of MTA1 nm23-H1 and E-cad was analysized by statistics, Results showed that the both former is also negative correlation with later(P<0.01), There is a positive correlation between later both(P<0.01).Conclusions1. The positive rates of MTA1 protein expression in normal mucosa tissues, atypical hyperplasia tissues of the tumor-adjacent and squamous carcinoma tissues of esophagus were high in turn and presented significantly difference. It indicated that MTA1 may be involved in the occurrence and development of squamous carcinoma of esophagus.2. The expression of MTA1 in esophageal squamous cell carcinoma tissues with lymphnode metastasis was higher than that without lymphnode metastasis, which indicated there was correlation between MTA1 protein expression and metastasis of esophageal carcinoma.3. The positive rates of nm23-H1 and E-cad protein expressions in normal mucosa tissues, atypical hyperplasia tissues of the tumor-adjacent and squamous carcinoma tissues of esophagus were high in turn and presented significantly differences. It indicated that nm23-H1 and E-cad MTA1 may be involved in the occurrence and development of squamous carcinoma of esophagus.4. The expressions of nm23-H1 and E-cad in esophageal squamous cell carcinoma tissues with lymphnode metastasis were higher than those without lymphnode metastasis, which indicated there was correlation between nm23-H1 and E-cad protein expressions and metastasis of esophageal carcinoma.5. The positive rates of the expression of MTA1 protein were different in esophageal squamous tissues with different invasion depth, the positive rates of carcinomas tissues were increased gradually accompany with the invasion depth, and the protein positive rates which invaded to outer lay were higher than that invaded to low-muscle lay and deep-muscle lay. It indicated that there was correlation between the expression of MTA1 protein and the invasion of esophageal squamous.6. The positive rates of nm23-H1 and E-cad protein expressions were different in esophageal squamous tissues with different invasion depth, the positive rates of carcinomas tissues were decreased gradually accompany with the invasion depth, and the protein positive rates which invaded to low-muscle lay were higher than that invaded to outer lay and deep-muscle lay. It indicated that there was correlation between nm23-H1 and E-cad protein expressions and the invasion of esophageal squamous.7. There was a statistical correlation among the expressions of MTA1, nm23-H1 and E-cad protein. It indicated that MTA1, nm23-H1 and E-cad may play a synergistic effect during the process of occurrence, development, infiltration and metastasis of squamous carcinoma of esophagus.