Expression And Relationship Of KiSS-1, MMP-2 And MVD In Different Esophageal Tissues

Esophageal carcinoma(EC), one of the most common malignant carcinoma,has been a great threaten to people's lives and health. China, Henan province in particular, is a high incidence area of EC.It ranked 2 in all the reviewed survey of gastrointestinal cancer deaths. It is estimated that nearly 200,000 persons die of EC in all of the world each year. On account of the invasion and metastasis is an important reason leading to death, so discussing the mechanism of invasion and metastasis has become one of the hot topics in EC.The occurrence and development of tumor is a process of chages involving multi-stage, multi-step, multi-factor and polygene.Tumor metastasis suppressor gene inactivation and tumor metastasis-related gene activation are the material basis of human tumor formation, development and uncontrolled.Previous research found that the mutation and deletion of gene such as KiSS-1 and MMPs most closely related to the occurrence of malignant tumors.KiSS-1, first cloned in 1996, was an anti-oncogene. It has been proved that the absent expression of KiSS-1 was closely related with the invasion and matastasis of many malignant tumor.In recent years, there are several relevant studies about the close relationship of KiSS-1 and invasion and metastasis in the fields of breast cancer, gastric cancer, pancreatic cancer, lung cancer and so on. The mechanism of KiSS-1 negatively regulated the growth, invasion, metastasis of EC may be through restraining the removal of cells and the activityof MMPs. MMPs is a kind of zinc ion depended endopeptidase, which can divide all components of extracellular matrix. MMP-2 (matrix metalloproteinase-2, MMP-2), also known as gelatin enzyme A,is one of the most important enzymes which dividing the basement membrane among all the MMPs.It plays a great role in dividing all components of extracellular matrix and regulating tumor vessel formation by digesting IV, V, VII, X type plastic and flexible fiber. A lot of studies had proved that MMP-2 played a key role in invasion and metastasis of many malignant tumors, such as lung cancer, gastric cancer and so on. Furthermore, KiSS-1 and MMP-2 can inhibit the growth, invasion and metastasis of tumor by inhibiting the formation of tumor angiogenesis. There have no other report both in China and abroad so far except the relevant articles pulished by our team before.To further investigate the correlation between the expression of KiSS-land MMP-2, and explore the effective method of earlier detecting the formation, invasion and metastasis of EC, we detected the expression of KiSS-1 and MMP-2 in 62 normal examples,31 patients with adjacent atypical hyperplasia epithelium and 62 patients with EC by SP method. We also evaluated the MVD in the same 62 patients with EC by CD34 antibody. Besides, the relationship of KiSS-1, MMP-2 protein and MVD in ESCC was evaluated simultaneously. Our research aims to provide the mechanism and theory foundation of how to restrain the formation, development, invasion and metastasis in EC. 1. The KiSS-1 protein expression was detected in 62 cases of normal esophagus mucous membrane tissue,31 cases of adjacent atypical hyperplasia tissue and 62 cases of EC by immunohistochemical SP method, then explored its clinicopathologic significance.2. The MMP-2 protein expression was also detected in 62 cases of normal esophagus mucous membrane tissue,31 cases of adjacent atypical hyperplasia tissue and 62 cases of EC by immunohistochemical SP method, then explored its clinicopathologic significance.3. Detected CD34 protein expression in 62 cases of EC by immunohistochemical SP method, then explored its clinicopathologic significance simultaneously.4. Discussed the relevance and significance of KiSS-1, MMP-2 and MVD by detecting the KiSS-1, MMP-2 and CD34 protein expression.5. Statistical analysis:Statistics analysis was performed by SPSS 10.0 software, adopt chi-square test, T test and ANOVA, test standard a is 0.05.1. The KiSS-1 protein expression rate in normal esophagus mucous membrane tissue, adjacent atypical hyperplasia tissue and esophageal squamous cell carcinoma tissue was 90.3%(56/62),67.7%(21/31) and 56.5%(35/62) respectively, and with a significant difference in group comparison (P<0.05); KiSS-1 protein masculine expression rate in infiltration depth of lower muscular layer group and deeper muscular layer group were 100%(7/7) and 50.9%(28/55) respectively, with a significant difference in group comparion (P <0.05); KiSS-1 protein masculine expression rate in lymphatic metastasis group was 35.0%(7/20), significantly lower than those without lymph node metastasis in EC was 66.7%(28/42), and with a significant difference in group comparion (P<0.05). KiSS-1 protein masculine expression in grade ofⅠ,ⅡandⅢwere respectively 66.7%(10/15),56.0%(14/25),50.0%(11/22), and no statistically significant difference (P> 0.05);2. The MMP-2 protein masculine expression rate in normal esophagus mucous membrane tissue, adjacent atypical hyperplasia tissue and esophageal squamous cell carcinoma tissue were respectively 22.6%(14/62),54.8%(17/31) and 71.0% (44/62), and with a significant difference in group comparison (P<0.05); KiSS-1 protein masculine expression rate in infiltration depth of lower muscular layer group and deeper muscular layer group were 28.6%(2/7) and 76.4%(42/55) respectively, with a significant difference in group comparion (P<0.05);KiSS-1 protein masculine expression rate in lymphatic metastasis group was 90.0% (18/20), significantly higher than those without lymph node metastasis in EC was 61.9%(26/42),and with a significant difference in group comparion (P<0.05); KiSS-1 protein masculine expression in grade ofⅠ,ⅡandⅢwere respectively 46.7%(7/15),72.0%(18/25),86.4%(19/22), the difference was statistically significant (P<0.05).3. The MVD values infiltrated to shallow muscular layer and those which infiltrated deeper layer were respectively 28.1±8.1 and 40.8±9.1,the difference among groups make statistics sense(P<0.05); The average MVD values in grade ofⅠⅡandⅢwere respectively 32.3±4.9,38.6±8.3, and 45.1±10.6,the difference between two groups was statistically significant (P<0.05); The average MVD values in EC with lymphatic metastasis(51.2±6.1) is signifcantly higher than those which without lymphatic metastasis(33.8±5.0),the difference among groups make statistics sense(P<0.05).4. The protein expression of KiSS-1 and MMP-2 was negatively correlated (rs=-0.418, P<0.05); The average MVD values in EC which KiSS-1 protein expression is negative was significantly higher than those KiSS-1 protein expression is positive (P<0.05).1. The KiSS-1 protein expression rate depress by turns in normal esophagus mucous membrane tissue, adjacent atypical hyperplasia tissue and esophagus cancer tissue, and there was a close correlation with the infiltration depth and lymph node metastasis, which suggest that the missing or lower expression of KiSS-1 may be related to the occurrence of EC. It is also closely related to the development, invasion and metastasis of EC.2. The MMP-2 protein expression rate boost by turns in normal esophagus mucous membrane tissue,adjacent atypical hyperplasia tissue and esophagus cancer tissue,and there was a close correlation with the infiltration depth,differential grade and lymph node metastasis,which suggest that MMP-2 may be involved in the occurrence and development of EC.It is also closely related to the process of invasion and metastasis in EC;3. The MVD value was closely related with the infiltration depth, differential grade and lymph node metastasis, which suggest that there was a close correlation with tumor biological behavior. MVD may become one of important assistant indexes in the early diagnosis and prognosis of EC, further providing a theoretical basis for gene therapy to block the tumour blood generation;4. The average MVD value in EC which KiSS-1 protein expression is negative was significantly higher than those KiSS-1 protein expression is positive, while the average MVD value in EC which MMP-2 protein expression is positive was significantly higher than those KiSS-1 protein expression is negative. There was a negative correlation beween the expression of KiSS-1 and MMP-2 protein by immunnohistochemical SP method and by Spearman rank correlation analysis (r,=-0.418, P=0.001).All of these conclusions prompt that joint detection of KiSS-1, MMP-2 and MVD is expected to be an indicator of judging the prognosis of EC, further provide the theoretical basis of inhibiting tumor recurrence and metastasis.