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Clinicopathological Significance Of PTEN And Caspase-3 Expression In Breast Cancer

Posted on:2005-11-09Degree:MasterType:Thesis
Country:ChinaCandidate:X F YangFull Text:PDF
GTID:2144360122991048Subject:Oncology
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Breast cancer is one of the most common malignant tumor that hurts female health. Incidence of the disease has showed sharply ascending trend in recent years. The age of onset goes to younger, and metastasis is the major dead course of patients with breast cancer. Therefore breast cancer is attached importance doubly. PTEN, a tumor suppressor gene(TSG) was found by Stecks and two other research groups in 1997, and was located on chromosome 10q23. 3. Up to now, PTEN gene is the first one that encodes a dual specific protein - phospho-lipid phosphatase. As a TSG, PTEN makes a great contribution to cellular differentiation , reproduction and apoptosis, as well as cellular adhesion and mobility , which is involved in regulation of a varity of signal transduction pathways and other biological courses. In addition, it has been proved that apoptosis is the result of Caspase cascade reactions and Caspase - 3 is located on downstream position of the reactions. As an effector, Caspase -3 playes an important role by degrading numerous substances, which directly leads to apoptosis with other Caspase members. The inactivation or reduced expression of Caspase - 3 was related to tumorigenesis and progression of many tumors based on previous reports. Now little is known about the relationship between the expression of PTEN and Caspase - 3 protein and tumorigenesis, differentiation, biological behavior and outcome of breast cancer. In order to analyze the relationship between the clinicopathological features and the expression of PTEN and Caspase ?3 protein, we detected the expression of PTEN and Caspase - 3 protein by immunohistochemi-cal method. The purpose of our study was to discuss the possible biological significance of the PTEN and Caspase - 3 protein in the tumorigenesis and progress of breast cancer, and the possible molecular pathological mechanism.Materials and Methods1. PatientsNinty - five cases of paraffin - embedded specimens of breast cancer were derived from Cancer Institute of China Medical University, including 4 cases of non - infiltrative carcinoma, 3 cases of early infiltrative carcinama, 7 cases of infiltrative specific carcinama and 81 cases of infiltrative non - specific carcinama. In addition, fifteen cases of benign breast lesions were selected as control group. None of the patients had received radiotherapy chemotherapy and other treatment before operation. The full clinical data and follow - up data had been collected. The mean age was 44 years (range from 22 -74) , and the mean follow - up time was 72 months.2. Method and Evaluation of ImmunostainingThe expression of PTEN ( mouse anti - human monoclonal antibody, 1:50 dilution, Zhongshan Biotechnology Company, Beijing) and Caspase -3 protein (rabit anti - human polyclonal antibody, 1: 100 dilution, DAKO Company, USA) was detected by immunohistochemical method. Clearly brown staining restricted to cytoplasm or nucleus was considered as positive expression of PTEN protein , and Caspase - 3 was localized in the cytoplasm. From 5 randomly selected representative fields of each section, according to semi - quantitatively integral method, the degree of immunostaining was graded as follows-, positive ones in counted cells; 0, positive rate <5% ; 1,5% -25% ; 2, 25% -50% ; 3, 51% -75% ; 4, >75% ; staining intensity: 1, yellow; 2, goldenness; 3, brown. Hie both integrals were multiplied: 0 score was defined as negative or loss of expression ( - ) ; reduced expression ( + ) : 1-6 scores; positive expression ( + + ) : 8 - 12 scores. On survival analysis, PTEN ( + ) and ( + + ) were regarded as PTEN positive expression group.3. Statistical AnalysisSPSS12.0 software was employed to analyze all data. Statistical evaluation was performed using Chi - Square test, Kendalls test, survival analysis. P <0. 05 was considered as statistical significance.ResultsThe expression of PTEN protein was observed in whole control group. Clearly brown staining was restricted to cytoplasm or nucleus of ductal or mammary gland' s epithelium. Thirt...
Keywords/Search Tags:breast cancer, tumor suppressor gene, PTEN, apoptosis, Caspase-3, prognosis
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