The Analysis Of Different Driver Genes In Lung Adenocarcinoma

Lung cancer causes the largest number of cancer related deaths worldwide.Currently,more than 85%of lung cancer cases are classified as non-small-cell-lung cancer(NSCLC),lung adenocarcinoma is the most common histological type of NSCLC.Lung adenocarcinoma not only presents heterogeneous histologically,but also shows significant differences in genome architecture.Currently a higher than 50%estimated frequency of actionable oncogenic drivers have been identified in lung adenocarcinoma.Targeted therapies have been succeeded in a subset of lung adenocarcinoma patients with driver oncogenic mutations.For example,drugs targeting EGFR mutations and ALK translocations have been successfully used in clinical medicine.The recognition of driver genes mutations in NSCLC is the basis of targeted therapy with inhibitors.Recently,several solid malignant tumours have been found to be genetically heterogeneous.For example,the hormone receptor status in primary tumours and metastatic/recurrent tumours were inconsistent in 20%-25%breast cancer patients.This study detected the expression of ALK gene translocation in lung adenocarcinoma and compared the ALK status between primary tumours and corresponding metastatic lymph nodes.In addition,ALK gene translocation was previously found to be mutually exclusive with other driver genes mutations.However,several recent reports have identified an overlap between ALK gene translocation and other driver genes mutations.Therefore,we examined the prevalence of ALK gene translocation and its coexistence with other driver oncogenes.They will be useful to further researches,individualized treatments and diagnosis of lung adenocarcinoma.The contents of this study are divided into two sections as followed:Section 1:We collected 106 ALK-positive lung adenocarcinoma cases which were stained by the Ventana ALK D5F3 immunohistichemistry.None of the patients received any treatment before surgery.We examined the prevalence of ALK gene translocation and its coexistence with other driver oncogenes by directly sequencing the EGFR,KRAS,BRAF,HER2 gene mutations.The results showed that EGFR gene mutations were detected in 5(4.7%)cases.However,KRAS,BRAF,HER2 gene mutations were not detected in all specimens.Three cases with deletions in exon 19,whereas two had mutations in exon 21.In addition,90 ALK-negative lung adenocarcinoma cases were selected as negative control to explore the clinicopathological characteristics of ALK positive cases in Chinese population.The results showed that ALK positive cases were more common in younger patients,and were more likely to have lymph node metastasis.Compared with ALK negative patients,ALK positive cases presented at a higher clinical stage.Although ALK-positive cases were not significantly associated with acinar predominant growth pattern,they were positive associated with micropapillary predominant growth pattern and solid predominant growth pattern.Section 2:We examined the ALK expression in lung adenocarcinoma and compared the ALK status between primary tumours and their metastases in 37 ALK positive and 16 ALK negative cases,as well as their corresponding metastatic lymph nodes by using the Ventana ALK D5F3 IHC.All cases showed diffused cytoplasmic staining pattern in the section of FFPE.No discordant case of ALK expression was observed between the primary tumour and corresponding lymph node metastasis.