The Expression And Significance Of EGFR, CTEN And E-cad In Non-small Cell Lung Cancer

Background and PurposeAccording to the third review cause of death investigation report shows that lungcancer has become the first in the malignant tumors cause of death, accounting for22.7%of malignant tumors.In the past30years,lung cancer mortality increase of464.84%,becoming China’s the fastest-growing,the most serious malignanttumors.Non-small cell lung cancer(NSCLC) in the lung cancer accounts for80%,because the majority of patients with lung cancer were found to have beentransferred,so75%of patients had not operated when they were diagnosed.Ability toenhance tumor cell invasion is an important factor in the occurrence and progressionof metastasis start.In these steps,genes,signal transduction pathway and factorinteractions participate.The prognosis of malignant tumors and tumormetastasis-associated protein closely related,so look closely associated with cancermetastasis-specific proteins, providing new targets for clinical treats.Epidermal growth factor receptor is a transmembrane receptor glycoprotein withtyrosine kinase activity,the epidermal growth factor family, also known as ErbB-1,HER1.It consists of three parts extracellular domain,a transmembrane region andintracellular domains;EGFR ligand binding to its dimerization, phosphorylation itself,thereby activating downstream signaling pathways.Currently,the specific studies withEGFR-related signaling pathways are two: Ras-MAPK signal transduction pathway,the signal transduction pathway activation and cell proliferation; another is PI3K-Akt signaling pathway, the pathway related to cell migration enhancements, the activationof this pathway conduction seen as epithelial-mesenchymal transformation (EMT) ofthe core features.Therefore,the signal transduction are closely related to umorangiogenesis formation, invasion and metastasis.EGFR in many human cancer cellsoverexpressing, including colorectal cancer, pancreatic cancer,head and neck cancer,gastric cancer,non-small cell lung cancer,etc.CTEN is tensin family member, tensin family member has already confirmed atotal of four.It studies show that tensin family proteins play a role in regulating of cellshape, migration, signal transduction.Four members each having a C-terminal PTBdomain(phosphotyrosine a binding domain) and SH2domain(SreHomolo stay2domaln).The results are shown, PTB of Tensin structural protein region, generallydo not combine tyrosine phosphorylated proteins, but integrins combined;SH2domains may be combined with PI3K, FAK (Focal Adhesion Kinas) and pl30Cas(p13oCrk-associated substrate), it is associated with many malignancies.CTEN wascloned in2002, the gene is located on human chromosome17q21region,cDNA fulllength4015bP, encoding715amino acids, containing six potential tyrosinephosphorylation sites.Initially, it was found to reduce CTEN expression in prostatecancer tissues.However, more and more studies show CTEN in other tumors oftenhighly expressed, such as breast cancer, colon cancer, gastric cancer.Therefore,CTEN is thought to play an important role in the regulation of tumor cellmorphology, migration,and signal transduction process.Epithelia cadherin(E-cadherin,E-cad) is a calcium-dependent cell adhesionmolecule adhesin family.E-cad protein expression in epithelial cells, by participatingin signal transduction and cell adhesion molecules that control morphologicaldifferentiation and tissue, and epithelial tissue involved in maintaining the structuralintegrity and adhesion epithelial cells.Research reports, E-cad protein overexpressedin epithelial cells can inhibit cell proliferation and migration, but also can induceapoptosis.In addition, the malignant tissue E-cad protein function obstacles, leadingto reduced adhesion between tumor cells,cells from the primary tumor and theoccurrence of local or distant metastasis.The study showed that the expressionreduction in tumor of E-cad, reducing mechanisms: E-cad gene deletion or mutation, promoter hyper methylation transcription suppression, post-transcriptional regulation.Currently,the expression and relationships in NSCLC of EGFR,CTEN and E-cadless reported in the literature;by immunohistochemical SP methods express ofEGFR,CTEN and E-cadherin;exploring the relation in between the expresses andpathological type, degree of differentiation, TNM stage and lymph node metastasisand other clinicopathological features;analysing the correlation between the three,providing biological indicators.Investigate EGFR,CTEN and E-cad protein in theNSCLC occurrence,development,invasion and metastasis,for early diagnosis andclinical treatment the NSCLC provide new ideas.Materials and Methods1.Object of studySelect the Second Affiliated Hospital of Zhengzhou University, Department ofThoracic Surgery March2012to March2013resected NSCLC tissues and82casesof lung cancer adjacent tissues54cases (HE staining were confirmed bypathology).According to UICC staging version2009TNM staging criteria.Allpatients who not radiotherapy chemotherapy and biological had complete clinical andpathological data.2.MethodsThe selected paraffin blocks made on4μm thick slice slicer, according to SPimmunohistochemical method to detect,strictly steps accordance with the kitinstructions;antibody diluted1:100.PBS solution instead of primary antibody ascontrol, EGFR, CTEN and E-cad positive biopsy was positive as controls.3.The results of immunohistochemistry method for determiningThe results determine the double-blind method,and also by two seniorpathologists independly observated each slice determination using criteriasemi-quantitative scoring method.According to staining intensity and number ofpositive cells as criteria: staining intensity scored:0divided colorless,1dividedyellow,2divided brown,3divided tan;the percentage of positive cells scored:0divided into negative, to10%for1points, to50%for2points, to75%of the3points,>75%of4points.According to staining intensity score and percentage ofpositive cells multiplied score≥4points,compared with positive expression.E-cad protein was mainly localized in the cell membrane and cytoplasm, brownish yellowgranular material.E-cad protein criteria:the number of positive cells≥70.0%for thenormal expression,counted as positive,<70.0%for the abnormal expression of thatexpression down, counted as negative.4.Statistical MethodsAll data were statistically analyzed by SPSS17.0software:χ2test normal lungtissue and cancer tissue differences in the expression of three proteins, and analyzethe relations between in three protein in the expression of cancer tissue andclinicopathological figure;Spearman correlation analysis of three proteins carcinomaassociation;α=0.05level for the test.Results1.The expression of EGFR, CTEN and E-cad protein in normal lung tissue, NSCLCtissuesEGFR protein that was mainly localized in the cell membrane and (or) thecytoplasm were brown particles;CTEN expressed mainly in the cytoplasm, paleyellow to brown granules;E-cad protein that was mainly localized in the cellmembrane and cytoplasm were brown particles;EGFR protein expression rates inNSCLC and normal lung tissue of13.0%and58.5%, two significant differences werestatistically significant (χ2=33.242P <0.001);CTENprotein expression rates inNSCLC and normal lung tissue of0.0%and69.5%, two significant differences werestatistically significant (χ2=64.620P <0.001);E-cad protein expression rates inNSCLC and normal lung tissue of100.0%and28.1%, two significant differenceswere statistically significant (χ2=68.625P <0.001);2.The expression of EGFR,CTEN and E-cad protein in NSCLC tissue are related toclinicopathological featuresEGFR, CTEN and E-cad protein were not related to age, gender, histologicaltype patients (P>0.05), and significantly correlated with the degree of TNM stage,lymph node metastasis and differentiation (P <0.05).3.The relationship among EGFR, CTEN and E-cad in NSCLCThe EGFR expression in the NSCLC was positively correlated with the CTEN (r=0.626P=0.000);EGFR expression in the NSCLC was negatively correlated with the E-cad (r=-0.577P=0.000);CTEN expression in the NSCLC was negativelycorrelated with the E-cad (r=-0.353P=0.001).Conclusion1.The abnormal protein expression of EGFR, CTEN and E-cad play an important rolein the development of NSCLC occurrence.2.Currently,EGFR has become one of the treatment targets in the NSCLC; as apotential target for the treatment of NSCLC,CTEN and E-cad deserves further study.