The Expression Of Survivin And Rac1 In Lung Cancer And Their Clinical Significance

IntroductionInvasion and metastasis, two of the most important biological features of lung cancer, are the key factors deciding the prognosis of lung cancer patients. Since Survivivn and Rac1are are closely related to the genesis, development, invasion and metastasis of tumor, this research tries to justify the possibility of using these genes and their products as new molecular targets in the treatment for tumor metastasis and as major indicators in prognosis observation of patients by the investigation of the interaction relationship between the expression of Survivivn and Rac1 and clinical-pathological features in lung cancer and paracarcinoma with the method of immunohistochemistry S-P and RT-PCR technique.Materials and methodsImmunohistochemistry S-P method and RT-PCR technique were used to test the expression of Survivin and Racl in lung cancer and para–carcinoma.All tissue samples were collected from 69 cases of primary lung cancer in Liaoning Cancer Hospital and the First Clinical Academy of China Medical University during the time of March, 2007 to September, 2007. All the samples were fixed in 10% neutral formalin and embedded in paraffin. None of the patients has received radiotherapy and chemotherapy. Stredptavidin peroxidase method was used for inmmunostainny.Survivin positive criterion: cells whose cytoplasm or nucleus are stained to the color ranging from light yellow to brown under optical microscope can be judged as positive cells. Cells were scored both by the number of stained cells and the staining intensity. If the product of the two above was≥1, the cells were positive; if≥4, strong positive. The number of stained cells was scored as 0 indicating≤5% cells are positive; 1 5%-25%; 2 25%-60%; 3≥60%. The staining intensity was scored as 0 indicating colorless; 1 light yellow; 2 yellow; 3 brown.Rac1 positive criterion: normal bronchial mucosa epithelial cells staining and known positive tissue were served as positive controls, and PBS buffer was used as negative control.Five high power fields were randomly selected for each section and 100 tumor cells were counted for each HP. The extent of staining was scored as(-), (+)indicating≤25% of cells were positive; (++)26-75%; (+++)≥76%. If Rac1 was normal, the expression should be negative or slight, whereas there was an enhanced expression in cancer tissues.Compared with the result of Horiuchi's Immunohistochemistry Rh. GTP test of ovarian carcinoma, (-)-(+) were defined as normal and (++)-(+++) as over expressed. All the data from S-P method was analyzed by SPSS for Window 10.0, and the result of P<0.05 was significant in statistics when the analysis was performed with the Pearson chi-square test.ResultSurvivin and Rac1 were weakly expressed in normal lung tissues and normal bronchial mucosa epithelial cells, on the contrary, were over expressed in pulmonary squamous carcinoma and pancreatic carcinoma (see Picture 1A ). The statistic analysis showed significant difference (p<0.01).The overexpression of Survivin showed significant difference in differentiation degree, stages and lymphatic metastasis (p<0.01) but not in gender, age and the histological type of lung cancer (p>0.05). The overexpression of Rac1 was related to the histological type of lung cancer but there were no correlations with age, gender, histological type, clinical stage or lymphatic metastasis.In pulmonary squamous carcinoma, the difference between the positive expression of Survivin protein and the expression of Rac1 protein was significant; furthermore, they two were positively correlated with each other. This indicated that there was a kind of synergism between the two but the mechanism of it remained to be studied. Discussion1. The relationship between Survivin, Rac1 and tumorSurvivin protein expression was closely related to the pathological classification of tumor, lymphatic metastasis and TNM stages, but bears no correlation with the patient's age, gender and pathological types. This result indicated that the high expression of Survivin could warn the high invasiveness and poor prognosis of squamous cell carcinoma. Consequently, it offered reference indexes for biological behavior evolution and poor prognosis of squamous cell carcinoma. The outcome of the reach is consistent with that of Monzo's reach in lung cancer and Sarela's research in colorectal carcinoma.Rac1, as has been proved in foreign researched, is a kind of RhoGTPase, which was proved to be high expression in many human tumor such as breast carcinoma, lung cancer, colon cancer, and ovarian cancer and no or low expression in normal tissue. The expression level is concerned with the differentiation degrees of tumor cells and their invasive and metastatic capacity. The result of the immuno-histochemistry in this research indicates that the high expression of Rac1 is only related to the differentiation degree of the tumor (p=0.04<0.05), rather than age, gender, stage of clinical–pathology and lymph node metastasis.Since the higher the differentiation is the lower the expression is, there is a negative correlation between the protein expression of Survivin and Rac1 and its differentiation degree in pulmonary squamous carcinoma. Survivin's relations to stages of cancer and lymphatic metastasis, which Racl doesn't own, shows that Survivin is a better index for the malignant degree of pulmonary squamous carcinoma and its prognosis. Rac1, on the other hand, is more reliable to solve the problem of"cancer or no cancer"problem. The significant correlation between the expression of Survivin and that of Rac1 indicates that both of the two played important roles in the genesis and development of tumor. The exact mechanism of the correlation requires further research.ConclusionThe expression of Survinvin and Rac1 in pulmonary squamous carcinoma is up regulated and the over expressions are concerned with the degree of differentiation of tumor. Besides, Survivin is also connected to the stages and metastasis of lung cancer. Rac1, on the other hand, neither shows this kind of feature nor significant correlation to other clinical pathological factors. Survivin could be served as an independent indicator of the diagnosis and prognosis of pulmonary squamous carcinoma. At the same time, both Survivin and Rac1 could be taken as targets in the therapy of tumor.