Expression Of Survivin Correlates With The Expression Of P53 And Ki-67 During Human Colorectal Oncogenesis

Background and ObjectiveSurvivin, a novel member of the inhibitors of apoptosis protein (IAP) family, is a mitotic spindle-associated protein involved in linking mitotic spindle function to the activation of apoptosis in mammalian cells. The structure of full-length human survivin determined by X-ray crystallography is 2.7 A? The structure forms a very unusual bow tie-shaped dimer. The unusual shape and dimensions of survivin suggest that it serves as an adaptor through its alpha-helical extensions. Survivin can suppress apoptosis through direct combination with caspase3 and caspaseV. The common pathway of apoptosis is the activation of caspaseS and caspase?, hence high expression of survivin may protect cells from many apoptosis signals and help cells survive. The other important function of survivin is that it can regulate the cell cycle in the G2/M phase by interact with spindle microtubules. It has been reported that survivin is undetectable in terminally differentiated adult tissues and becomes prominently expressed in most common human cancers. Some data indicated that high expression of survivin enhances viability of cells and leads abnormal cells toovercome apoptotic checkpoint and proliferate extraordinarily. Now, substantial data have shown that inhibition of apoptosis plays a great role in carcinogenesis, so survivin may play an important role in the development of carcinoma with other oncogenes together. In this study, we investigated the expression of survivin in human colorectal adenomas with malignant transformation, and whether the expression of survivin correlates with either the expression of p53 or the imbalance between cell proliferation(mean Ki-67 LI) and apoptosis. Furthermore, we try to search for some index in the early diagnosis of malignant transformation of an adenoma.Materials and MethodsSpecimens used for this study were composed of 10 normal colorectal mucosa and 61 colorectal adenomas with both mild dysplasia( I or II grade dysplasia ) and severe dysplasia(III grade dysplasia). All of these adenomas had been transformed into malignance partly which were resected surgically or endoscopically at the first Affiliated Hospital of Zhengzhou University from 1996 to 2002. The immunohistochemical staining for survivin, p53 and Ki-67 antigens was carried out by the standard streptavidin-peroxidase(SP) technique.ResultsLocalization of Survivin, p53 protein and Ki-67 antigen The expressions of survivin were observed in cytoplasm of tumor cells, whereas the expression of p53 and Ki-67 proteins were predominantly in the nucleus. No immunoreactivities of survivin or p53 protein were observed in normal mucosa. In contrast, expression of Ki-67 antigen was detected not only in tumor cells, but also in normal mucosal cells where these cells are mainly in the regenerative crypt base.Changes in Expression of Survivin during the Malignant Transformation of Colorectal Adenomas The immunoreactivity of survivin increased gradually during colorectal tumorigenesis. The positive rates for survivin in mild dysplasia, severe dysplasia and malignant areas were 26.2%, 52.5% and 62.3% respectively. The immunoreactivity of survivin in adenomas significantly increased in the transition from mild dysplasia to severe dysplasia(P < 0.05), and compared the mild dysplasiawith the malignance, the differences were still significant(P < 0.05). Whereas, there were no significantly differences in the expression of survivin between severe dysplasia and malignance(P > 0.05).Changes in Expression of p53 protein during the Malignant Transformation of Colorectal Adenomas Similar to the expression of survivin during colorectal tumorigenesis, nuclear accumulated p53 protein also increased gradually in the malignant transformation within adenomas. The positive rates for p53 protein in adenomas with mild dysplasia, severe dysplasia and malignant areas were 19.7%, 57.4% and 67.2% respectively. Compared the mild dysplasia with severe dysplasia and malignance respectively, the immunoreactivities of p53 protein both i...