Expression And Mutational Analysis Of Receptor Of Tyrosine Kinase In Neuroendocrine Lung Carcinoma

Objective: To investigate the effect of the expression of KIT and PDGFR protein and their relationships with clinical pathology and prognosis of neuroendocrine tumors of the lung by immunohistochemical stain, and detect the mutations of exon 9 and 11 of c-kit gene in small-cell lung cancer. Then discuss the development of tyrosine kinase inhibitors for the treatment of neuroendocrine tumors of the lung.Methods: To collect 63 neuroendocrine tumors of the lung resection samples with complete clinical and prognostic data. To carry through c-KIT, PDGFR-a and PDGFR-βImmunohistochemistrical(IHC)staining and study the relationships between c-KIT, PDGFR- a and PDGFR-βand prognosis, clinicalopathological parameters. Polymerase chain reaction (PCR) was used to amplify exon 9 and exon 11 of c-kit gene in 13 SCLC cases, and the PCR products were sequencing directly.Results:1. The expression of c-KIT, PDGFR-a and PDGFR-βprotein in neuroendocrine tumors of the lung.The rate of immuno-positive staining of c-KIT protein in neuroendocrine tumors of the lung was 42.9% (27/63), in which the rates in large-cell neuroendocrine carcinoma, carcinoid and clear-cell carcinoma types were 30.8% (8/26) ,42.9% (6/14) and 56.5% (13/23). The rate of immuno-positive staining of PDGFR- a protein in neuroendocrine tumors of the lung was 58.7% (37/63), in which the rates in large-cell neuroendocrine carcinoma, carcinoid and clear-cell carcinoma types were 26.9% (7/26),64.3%(9/14) and 91.3% (21/23).The rate of immuno-positive staining of PDGFR-βprotein in neuroendocrine tumors of the lung was 66.7% (42/63), in which the rates in large-cell neuroendocrine carcinoma, carcinoid and clear-cell carcinoma types were 50.0% (13/26), 71.4% (10/14) and 82.6% (19/23).2. Survival analysisThe Kaplan-Meier survival analyzes show that the survival rate of the patients with large-cell neuroendocrine carcinoma is significantly different between groups with or without the expression of PDGFR- a protein. The survival time of the positive group is significantly shorter than the negative group(Log-Rang:4.28, P＜0.05). The Kaplan-Meier survival analyzes also show that the survival rate of the patients with carcinoid is significantly different between groups with or without the expression of PDGFR--βprotein. The survival time of the positive group is significantly shorter than the negative group(Log-Rang=4.50, P＜0.05).3. Mutation analysis of c-kit in SCLC.One out of 13 SCLC (7.7%) revealed mutations in exon 9, while 5 of 13 SCLC (38.5%) revealed mutations in exon 11. The mutations pattern consisted of point mutation and insertion mutation.Conclusion:1. There are the expressions of c-KIT, PDGFR- a and PDGFR-βprotein in neuroendocrine tumors of the lung which suggests that the occurrence and evolution of neuroendocrine tumors of the lung concerns the overexpression of receptor tyrosine kinase protein nearly. The results show the possibility of tyrosine kinase inhibitors for the treatment of neuroendocrine tumors of the lung.2. The survival analysis show that the correlations between the expression of receptor tyrosine kinase and neuroendocrine tumors of the lung.3. There was one of 13 SCLC revealed mutations in exon 9, and 5 of 13 SCLC revealed mutations in exon 11. which mutations including point mutation and insertion mutation.