Expression And Clinical Significance Of Telomeric Repeat Binding Factor 1 In Non-small Cell Lung Carcinoma

Background and ObjectivePrimary lung cancer is one of the most frequent male malignant disease in the world,and it located first death rate in the all malignant tumor.which is seriously threatening the health of the people.Non-small cell lung carcinoma (NSCLC)is account for 80-85%of all lung cancers.So it' s very important significance to study the etiopathogenisis of non-small cell lung carcinoma. Now,It is not completely distinctness the etiological factor and pathogenesy of lung cancer.Nowadays,the relationship of telomere and telomerase with tumor have in-depth study.Telomeres are specialized protectives tructures at the extreme ends of eukaryotic chromosomes,which consist of tandem repetitive DNA sequences and binding proteins.Telomere dysfunction is associated with chromosomal instability which is implicated in ageing and carcinogenesis.The function of telomere mainly depend on keeping it's length and construction.The vast majority of mammalian cells maintain their telomere length by telomerase. There is increasing evidence suggesting that both the maintenance of telomere length and structure and telomere elongation by telomerase are regulated by telomeric binding proteins.The first human telomeric repeat binding factor discovered by Chong.It's negatively regulating factor of telomere length. TRF1 interfere with telomerase connect chromosome ends and indirectly regulate telomere length.There is study that know the Expression and Clinical Significance of TRF1 in a lot of tumour cell.but the study of Expression TRF1 in Non- small Cell Lung carcinoma is rare,so the aim of this investigation is detecting the significance of the expression of TRF1 in NSCLC and it's relationship with clinical index,and providing assistance of clinical treatment and decision of prognosis.Objects and MethodsIn the study,expressions of TRF1 were detected in a group 40 paraffin-embedded samples from surgically resected non-small cell lung carcinomas,using immunohistochemistry(EnVision methods).Control group are normal tissue at side of cancer from the 37 patients that in the same group.Relationship between clinicopathologic characteristic,survival and expressions of TRF1 was analyzed.All samples are from Taizhou Hospital of zhejiang province patients who were diagnosed as primary NSCLC histopathologically.All patients include Squamous cell cancer (22),adenocarcinoma(13),bronchioalveolar carcinoma(3),adenosquamous carcinoma(1)and large cell carcinoma(1).25 males and 15 females,aged 41 to 71yrs,the mean age was(51±7.8)yrs.All tumors were staged according to the International Union Against Cancer TNM stage system(1997)after the surgery:Ⅰstage 9,Ⅱstage 16,Ⅲa stage 12,Ⅲb stage 3.23 example of NSCLC have lymphaden transferred in 40 NSCLC.All tumor samples were paraffin-embedded.Tumor sections were cut by 4μm, and deparaffinaged to hydration.In the study,expressions of TRF1 were estimated using immunchistochemistry(EnVision methods).Phosphate buffered saline were used with first antibodies as negative control,whereas lung cancer samples were used as a positive control.TRF1 was stained in the cytoplasm of tumour cell,and appeared Buffy or tan of positive granule,there is consider negative that cytoplasm and nuclei of tumour cell was not stained.The percentage of immunopositive cells in representative are as of the sections was assessed by two pathologists.The percentage of positive cells was evaluated as follows: 0,undetectable;1,less than 10%;2,11-50%;3,more than 50%.Those tumors in which the stained tumor cells made up 10%of the tumor were graded as positive. Expression of TRF1 in NSCLC and it's relationship with clinicopathologic characteristic,survival were analyzed.Counting data about the two groups were analyzed by Chi-squaretest with SPSS 11.0 for windows.P＜0.05 was regarded as statistical significance.The survival curves of patients with different expression of TRF1 by use of a Kaplan-Meier curve.Results1.Expression of TRF1 in Cancer and normal tissue at side of cancer:Expression of TRF1 is 57.5%positive in Cancer,expression of TRF1 is 8.1%positive normal tissue at side of cancer.A significant difference was compared between Cancer and normal tissue at side of cancer(P＜0.01).2.Relationship between expressions of TRF1 and clinicopathologic characteristic of NSCLC:Expression of TRF1 is 59.1%positive in squamous cell carcinoma,53.8%positive in adenocarcinoma and 60%positive in other type.No statistically significant was compared between them.Further,the expression of TRF1 demonstrate no statistical difference in groupes divided by gender,age,long-term smoking,tumor size,lymphonode involvement, pathological TNM stages,age,differentiated degree(P＞0.05).3.Relationship between expressions of TRF1 and overall survival rate of patient:overall survival rate of patient which expression of TRF1 is positive is 60.9 percentage,overall survival rate of patient which expression of TRF1 is negative is 64.7 percentage.There is no significant difference that was compared between them(P＞0.05).Conclusions1.There were higher positive expressions of TRF1 in NSCLC compared with normal tissue at side of cancer. 2.The expression of TRF1 in NSCLC is not related with histology type,gender, age,long-term smoking,tumor size,lymphonode involvement, pathological TNM stages,age,differentiated degree and prognosis.