The Expression And Significance Of Ezrin Protein In Non-small Cell Cancer

Aims:To study the expressions and clinical significances of Ezrin in non-small cell lung cancer(NSCLC).Material and methods:47 specimens(including tumorous tissues,paracancerous tissues and metastatic lymph node)of primary NSCLC and 19 specimens of benign pneumonic disease were collected from the Department of Chest Surgery,First Affiliated Hospital of Zhejiang University School of Medicine in 2007.The expression of Ezrin was detected with immunohistochemical staining,RT-PCR,and Western blot in these specimens.Then we studied the relationship between clinicopathological parameters and levels of Ezrin activation.These clinicopathological parameters included sex,age,tumor size,lymph node metastasis, differentiation,histology type,and histopathologic grading.68 specimens of NSCLC in 2000 were examined for Ezrin by immunohistochemical staining,and we studied the relationship between clinicopathological parameters(including the 3-year survival rate,the 5-year survival rate and the metastasis rate after the operation)and levels of Ezrin activation. Results:1.Immunohistochemistry:Ezrin expresses highly in NSCLC.It mainly locates in cytoplasm,but in some specimens it locates on cell membrane.The positive rates of Ezrin expression are higher in moderately than in poorly differentiated cancer tissues (82.12%vs.37.24%,p＜0.05);higher inⅢthan inⅠ,Ⅱstages(92.30%vs.23.33%, p＜0.05);higher in lymph node metastatic groups than in lymph node non-metastatic groups(92.00%vs.27.78%,p＜0.05);higher in adenous cancer group than in squamous cancer group(84.31%vs.49.59%,p＜0.05).Additionally,the positive rate of Ezrin membrane expression in lymph node metastatic groups is significantly higher than that in lymph node non-metastatic groups(54.32%vs.12.03%,p＜0.05).In 68 cases of lung cancer patients,28 cases recurred after the operation,37 cases did not recur,while 3 cases lost.The positive rate of Ezrin is higher in recurrence group than in non-recurrence group(90.47%vs.40.90%,p＜0.05).The 3-year survival rates are lower in Ezrin positive group than in negative group(22.45%vs.65.92%,p＜0.05); the 5-year survival rates are also lower in Ezrin positive group than in negative group (7.29%vs.46.47%,p＜0.05).2.Western-blot:The expressions of Ezrin and phosphorylated Ezrin are that:lung cancer＞paracancerous tissues＞benign pneumonic tissues(p＜0.05 for each).The expressions of Ezrin and phosphorylated Ezrin are closely relevant with differentiation,clinical stage,lymph node metastasis,and histopathologic type of NSCLC,and the details are as follows:the expression of the two proteins are much higher in moderately than in poorly differentiated cancer tissues(p＜0.05,the increases are 67.1%and 107.6%respectively);higher inⅢthan inⅠ,Ⅱstages (p＜0.05,the increases are 60.1%and 100.4%respectively);higher in lymph node metastatic groups than in lymph node non-metastatic groups(p＜0.05,the increases are 35.9%and 80.3%respectively);and higher in adenous cancer than in squamous cancer tissues(p＜0.05,the increases are 55.2%and 108.3%respectively).In lymph node metastatic group,the expressions of Ezrin and phosphorylated Ezrin protein are significantly higher in metastatic lymph nodes than in lung cancer tissues(p＜0.05). 3.RT-PCR:The expressions of Ezrin mRNA are that:lung cancer＞paracancerous tissues＞benign pneumonic tissues(p＜0.05 for each).However,the expressions of Ezrin mRNA are not relative with sex,age,tumor size,differentiation,clinical stage, lymph node metastasis,and histopathologic type of NSCLC.Conclusions:1.Ezrin is expressed highly in NSCLC at the mRNA and protein level,which suggests that Ezrin may play important roles in NSCLC.2.The expression of Ezrin and phosphorylated Ezrin protein are closely relevant with differentiation,clinical stage,lymph node metastasis,histopathologic type,while the expression of Ezrin mRNA is not relevant with them,which indicated that compared to mRNA expression,the Ezrin protein expression and protein phosphorylated modification play a much more important role in the development and transfer process of NSCLC.3.In different degree of differentiation,clinical stage,lymph node metastasis, pathological type of NSCLC,the expression of phosphorylated protein increased greater rate than of non-phosphorylated protein,which suggested that Ezrin may be activated by phosphorylation,and promote tumor metastasis.4.Ezrin expresses mainly in the cytoplasm,and on the cell membrane in some specimens.And the positive rate of membrane expression in lymph node metastatic groups is significantly higher than that in the lymph node non-metastatic groups.It suggested that the shift of Ezrin from the cytoplasm to membrane plays an important role in lung cancer transferation.5.The expression of Ezrin is relevant with postoperative recidivism rate and postoperative survival rate.The results suggested that Ezrin may be very valuable on the judgement of prognosis.