| Background and Objective:Gastric cardia adenocarcinoma (GCA) is one of the malignant tumors that threatens human’s health seriously. With the development of pathology and endoscopic diagnoses techniques, there are more and more GCA are detected as well as the research of its mechanism. Therefore, further exploring the alterations of key genes related to development and progression of GCA will be considered useful. In this study, We sought to investigate the expression of Skp2and p27kipl in different types of gastric cardia tissues, their clinical significance in GCA and the relationship between Skp2and p27kipl in GCA, in order to provide theoretical basis for early diagnosis and therapy of GCA.Materials and Method:(1) Tissue specimens used for this study were obtained randomly from110patients, which were resected surgically or endoscopically at Tianjin first center hospital from Jan.2009to Dec.2011.The samples including20normal controls,20intraepithelial neoplasia,70adenocarcinoma. All samples were pathology archive wax block and all the patients were not received preoperative radiotherapy, chemotherapy or immunotherapy.There are57male and13female in GCA, and the average age is71with a range of44-87years. there are19cases of Ⅰ-Ⅱ while51cases of Ⅲ-Ⅳ,14cases of serosal infiltration while56cases of none,28cases of lymph node metastasis while42cases of none.36cases of high or middle differentiatied while34cases of lower.(2) The expression of Skp2and p27kipl in20normal controls,20intraepithelial neoplasia,70adenocarcinoma is determined by immunohistochemistry (S-P).(3) The expression of Skp2mRNA in20normal controls,20intraepithelial neoplasia,70adenocarcinoma is determined by in situ hybridization.(4)The data were analysized by software SPSS17.0, chi-square test or Spearman correlation was used to compare between groups. P<0.05was considered as statistically significant value.Result:(1) The positive expression rates of Skp2mRNA in70adenocarcinoma,20intraepithelial neoplasia and20normal controls are72.90%(51/70),60.00%(12/20),30.00%(6/20) respectively.and Skp2protein in70adenocarcinoma,20intraepithelial neoplasia and20normal controls are68.60%(48/70),55.00% (11/20),20.00%(4/20) respectively significant difference (P<0.05) were found between the three groups..The up-regulation of Skp2expression was respective positively correlated with advanced clinicopathological stage, degree of differentiation and lymph node metastasis (P<0.05), significant difference (P<0.05) were found between the three groups.(2) The positive expression rates of p27kipl in70adenocarcinoma,20intraepithelial neoplasia and20normal controls are32.90%(23/70).55.00%(11/20)、85.00%(17/20) respectively, significant difference (P<0.05) were found between the three groups.The down-regulation of p27kipl protein was respective positively correlated with advanced clinicopathological stage, degree of differentiation and lymph node metastasis (P<0.05). significant difference (P<0.05) were found between the three groups.(3) The correlation analysis indicated that the expression of Skp2protein had a close negative correlation with that of p27kipl protein in adenocarcinoma (r=-0.531, P=0.000<0.05) significant difference (P<0.05) were found between the three groups.Conclusion:(1) The up-regulation of Skp2mRNA and Skp2protein in GCA proved that the expression of Skp2may be regulated at the transcriptional level. A increasing tendency from normal mucosa to advanced GCA reflects the biological behavior on the molecular level,which is benefit for the understanding of the formation of GCA and providing some implications for the effective preventation in the future.(2) The expression of Skp2mRNA and Skp2protein was respective positively correlated with clinicopathological stage, degree of differentiation and lymph node metastasis, which indicates Skp2may be the key factor of biologic behavior such as invasion, metastasis in GCA, and it provides some references for the evaluation of tumor malignancy.(3) p27kipl protein progressively decreased from normal controls, through intraepithelial neoplasia to adenocarcinoma, which indicates that the lost p27kipl protein may not make effective inhibition of cell proliferation, thus favoring the occurrence of GCA.(4) As the expression of p27kipl protein was respective positively correlated with clinicopathological stage, degree of differentiation and lymph node metastasis, it may take part in the biological behavior of GCA, too, and provides some clues for the evaluation of clinical prognosis of GCA.(5)There was a significant inverse correlation between the expression of Skp2and p27kipl, Skp2might play an important role in the development and progression of GCA via proteolysis of cyclin-depended kinase inbitor p27kipl.(6) It is helpful for clinical prognosis, diagnosis and evaluation of GCA to detect p27kipl and Skp2together. |
PDF Full Text Request