Expression Of HSP70 And Caspase-3 And Their Relations With The Tumor Histological Grade In Glioma

BackgroundsGlioma is one of the common tumors of human Centre Nervous System. The prognosis and predictive of glioma according as the WHO classification of tumors, but in some cases, such as the borderline pathological changes, heterogeneity of tissues, and choose the difference area of tumor tissues that could be bring on the difference histopathological diagnosis. Thus, only rely on the tumor histological grade could be not truly reflect the differentiation of glioma, and combine with the cell proliferation examination should be help for the diagnosis and treatment of tumor and understanding the mechanism of the carcinogenesis of glioma.Heat shock protein (HSP), also namely stress proteins, involved in a multitude of biological processes, including protection of nascent polypeptide chains from prematureaggregation, disaggregation of protein aggregates, polypeptide transport across biological membranes, and proteolysis, etc. HSP has function to regulate the protein active, and is not take part in the makeup of large molecule protein itself, so as "molecular chaperone". Recently studies show that some members of HSP family are over express in human tumor cells and tumor cell lines in vitro, and those proteins involved in tumor cellular functions, such as apoptosis and necrosis, that in favor of tumor cell gain advantage of survival. However, it is reported that HSP70 have function for promoting tumor cell apoptosis in some cases which should be have significance in diagnosis and treatment of tumor.Cysteinyl aspartate specfic protease (Caspase) family is a large set of apoptotic regulated genes for the initiation and execution of mammalian programmed cell death. Apoptosis may be thought of as a signaling cascade, which Caspase-3 is a key protease. In normal status, Caspase-3 as inactivity zymogen exists in some tissues and cells of mammalian, and overexpression in immunocyte, brain, and embryo cells. The irregulation of cell apoptosis result in the cell death reducing and uncontrolled proliferate that associated the development and progression of tumor. It is reported that Caspase-3 plays an important role in the cell apoptosis of the brain tumor. Moreover, the study associated Caspase-3 induced cell apoptosis in brain tumor, which treatment by radiotherapy and chemotherapy, show that the tumor development not only related the nervous cells abnormal proliferate, but also related the cells abnormal apoptosis.The present study use immunohistochemistry to investigate the clinical significance of HSP70 and Caspase-3 expression and analysis the relationship between the protein expression and the proliferation, apoptosis, and differentiation of cells in Glioma.Materials and MethodsPatients and specimensWe consecutively collected tumors from 50 patients (mean age, 36.7; range, 4-67 years; male: female, 31:19) who had undergone surgery for glioma at the Jinan General Hospital of the PLA from March 1999 to January 2005. The histopathological diagnosis was made according to the WHO classification: 8 cases were WHO I grade; 13 cases were WHO II grade; 13 cases were WHO HI grade and 16 cases were WHO IV grade.ImmunohistochemistryImmunohistochemical staining of HSP70 and Caspase-3 monoclonal antibody was done using the SP Staining System.Evaluation of immunostainingAll of the immunostained sections were reviewed by double blinded studies. For expression of Hsp70 and Caspase-3 protein, five areas (×400) were selected at random and scored in cases with multiple areas of high intensity that occurred during evaluation of immunostaining. The degree of immunohistochemical staining was recorded that considered the proportion of tumor cells with an unequivocal positive reaction (Area:—,≤5% staining; +, positive staining in 6%～25% of tumor cells; ++, positive staining in 26% to 50% of tumor cells; +++, positive staining in >50% of tumor cells).Results1 Immunohistochemistry were done to evaluate HSP70 and Caspase-3 protein expression, which show brown, respectively. The HSP70 protein expression had a cytoplasmic and nuclear staining pattern, and the Caspase-3 had a cytoplasmic staining in tumor cells.2 The HSP70 expressed intensity of tumor cells were increase with the histological grade up in Gliomas, and the percentage of stained tumor cells from histological grade I to IV was 25 %, 69 %, 92 % and 100%( P < 0.01), respectively. 3 The Caspase-3 expressed intensity of tumor cells were decrease with the histological grade up in Gliomas, and the percentage of stained tumor cells from histological grade I to IV was 87.5%, 61.5 %, 38.5% and 31% ( P < 0.01), respectively.4 Caspase-3 expression was reverse correlated with HSP70 expression (P <0.01) in Gliomas.ConclusionThe Caspase-3 and HSP70 protein expression are related to the biological behavior and differentiation of tumor cell in glioma. The immunohistochemical examination of Caspase-3 and HSP70 expression in glioma, which have difference histological grade, should be help for evaluated the tumor cell malignant degree and have significant to demonstrate the mechanism of the carcinogenesis of glioma.