| Lung cancer is the leading cause of cancer death in the world, non-small cell lung cancer represents80%of the total lung cancer. In2007, Japanese researchers first discovered the echinoderm microtubule-associated protein4-anaplastic lymphatic tumor kinase fusion gene in non-small cell lung cancer. EML4-ALK fusion gene is considered to be one of induced genes in lung cancer. ALK inhibitor therapy EML4-ALK fusion gene-positive non-small cell lung cancer patients with efficiency up to80%, So further research is necessary to explore the biological characteristics of EML4-ALK fusion gene and the relationship between expression and clinicopathological features in non-small cell lung cancer in local area.Objective:To investigate the expression of EML4-ALK in non-small cell lung cancer and adjacent tissues, correlation with the patient’s clinical data, analyze the relationship between the expression and the clinicopathological features of EML4-ALK fusion gene, In order to guide clinical ALK inhibitor use for the appropriate patients, and to further explore its significance as a new target for the diagnosis and treatment of NSCLC.Methods:Expression of EML4-ALK fusion gene were detected in245cases of non-small cell lung cancer and80cases of adjacent normal tissues by using immunohistochemistry and tissue microarray. Selected the surgery lung tissue specimens245cases which diagnosed with non-small cell lung cancer in First Affiliated Hospital of Yangtze University by two independent pathologists. collected their pathology and clinical data. The245cases of non-small cell lung cancer patients collected as the experimental group,80cases of adjacent normal lung tissue were randomly selected from245cases as a control group, collected patients’pathology and clinical data such as sex, age, smoking history, histological type, tissue differentiation and the clinical stage. Under the guidance of two pathology experts, choose a representative area of HE slice to production of tissue microarray. Use tissue microarray technology to detect EML4-ALK gene protein expression in non-small cell lung cancer tissue and adjacent tissues, by immunohistochemistry SP method. EML4-ALK-positive localized in the cytoplasm, showing brownish yellow. The criteria is random observation five high-power field, calculate the average, each vision counting100cells, based on the percentage of tumor cells positive cells accounted divided into:<10%for1point,10%-50%for2points,51%-75%for the three points,>75%for the four points, no positive cytoplasmic staining of0points,1point cytoplasmic staining yellow, brown cytoplasmic staining for2points, brown or granular cytoplasmic staining for the three points, more than3points was judged positive. All statistics were analyzed by statistical software SPSS17.0, application chi-square test, chi-square test and continuous calibration Fisher exact test, with P<0.05was considered statistically significant. Combined the result of immunohistochemistry and clinical pathological features for statistical analysis.Results.-The positive rate of EML4-ALK in non-small cell lung cancer was7.35%(18/245),higher than0%(0/80) in adjacent normal tissues with significance (P=0.027).EML4-ALK expression was significantly correlated with gender, smoking history, histological type and clinical stage (P<0.05). EML4-ALK fusion gene in18cases of non-small cell lung cancer is positive, the positive rate was7.35%, while the expression was negative in80cases of cancer adjacent tissue, There is a difference between the EML4-ALK gene expression in non-small cell carcinoma tissue and adjacent tissue, the difference was statistically significant (P=0.027), EML4-ALK gene expression in male patients with non-small cell lung cancer was5.06%, expressed in female patients with non-small cell lung cancer was13.43%.EML4-ALK gene expression in non-small cell lung cancer patients have a gender difference, and the difference was statistically significant (P<0.05). EML4-ALK gene expression in old(at age>60years) patients with non-small cell lung cancer tissues rates were5.10%, EML4-ALK gene expressed in young(at age>60years) patients with non-small cell lung cancer tissues rates were8.84%, the difference between them was not statistically significant. EML4-ALK gene expression in smoking patients was3.15%, in patients with non-small cell lung cancer who were non-smokers or light smokers (^10pack/years or quitting time of up to more than1year) was11.86%, the difference was statistically significant (P<0.05). The non-small cell lung cancer is divided into two major histological type, adenocarcinoma and non-adenocarcinoma (including squamous cell carcinoma, large cell carcinoma, and other types of non-small cell lung cancer). The expression rate of lung adenocarcinoma patients is14.91%, EMLA-ALK gene expression rate of non-adenocarcinoma patients was0.76%, the difference between the two was statistically significant (P<0.05). Based on the degree of tumor differentiation, it can be divided into three groups,there were well-differentiated. Moderately differentiated and poorly differentiated groups. EML4-ALK gene expression in well-differentiated group was4.55%, EML4-ALK gene expression in differentiated group was6.56 %,EML4-ALK gene expression rate was8.91%in poorly differentiated group, the difference was not statistically significant between the three groups(P>0.05). The positive rate of EML4-ALK in the low-stage group (I+II stage) in non-small cell lung cancer was5.14%, in the high-staging group (III IV stage) the EML4-ALK positive expression rate of12.56%, and this difference was statistically significant (P<0.05).Conclusion:EML4-ALK expression in non-small cell lung cancer was associated with clinical stage and may play important roles in non-small cell lung cancer’s development and metastasis.It may become a new target of clinical therapy. EML4-ALK gene expression in non-small cell lung cancer tissues was significantly higher than the adjacent tissues, and the staging of patients with high expression was significantly higher than in patients with low installments, which further confirmed that EML4-ALK fusion gene was a driver gene in non-small cell lung cancer and it plays an important role in transforming normal tissue to non-small cell lung cancer. In addition, EML4-ALK expression was significantly correlated with gender, smoking history, histological type and clinical stage.EML4-ALK expression in non-small cell lung cancer was associated with clinical stage and may play important roles in non-small cell lung cancer development and metastasis.It may become a potential target of clinical therapy. |
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