Expression Of C-Kit Protein In Small Cell Lung Cancer And Its Prognostic Implications

C-Kit is a member of the receptor tyrosine kinase subclass III family. Stem cell factor(SCF) is the cognate ligand for c-Kit. When c-Kit binds with SCF, it will active several signal transduction pathways and then play a role in the cell functions including survival , proliferation , differentiation , adhension and apoptosis etc. However several reasons can lead to ligand-independent kinase activity with resultant receptor autophosphorylation and stimulation of downstream signaling pathways in tumors, including mitogen-activated protein kinase and phosphatidyl inositol-3 kinase. Consequently the signal transduction is out of control, therefore result in the acceleration of proliferation and/or the reducement of apoptosis. Ultimately the cell with the mutation of c-Kit gene will obtain the advantage of viability. c-Kit expression has been documented in a wide variety of human malignancies, and the kinase activity of KIT has been implicated in the pathophysiology of a number of these tumors. Our study aimed to investigate the potential relationship between c-Kit protein and Small Cell Lung Cancer(SCLC), as well as its prognostic significance. Objective: To investigate the effect of the expression of c-Kit protein and its relationship with clinical pathology and prognosis of SCLC. To discuss the rationale for and development of tyrosine kinase inhibitors for the treatment of human SCLC.Methods: To collect 100 SCLC resection samples with complete clinical and prognostic data. To carry through c-Kit , Ki67 and Cyclin D1 Immunohistochernistrical(IHC)staining and study the relationships between c-Kit and cell proliferation, prognosis, clinicalopathological parameters. To establish COX regression model with patients' pathologiclinical data and molecules aforementioned and discuss their effects on patients prognosis. Results:1. The expression of c-Kit protein in SCLCThe positive expression of c-Kit protein was 50% (50/100). There was obvious relationships between the expression of c-Kit protein and the T grade. The expressional frequence of T2^ T3^ T4 is higher than Tl(P<0.05). The Cox regression analyze of patients' survival indicate that the main influenceable factors are gender(P<0.05)and the expression of c-Kit(P<0.001). The Kaplan-Meier survival analyze show that the survival rate of the patients with SCLC is significantly different between groups with or without the expression of c-Kit protein. The survival time of the positive group is significantly shorter than the negative group(Log-Rank=21.62, /><0.0001).2. The expression of Ki67 and Cyclin Dl protein in SCLC2.1 The expression of Ki67 protein in SCLC and its relationship with c-Kit protein.All the cancer tissues in two different groups showed positive expression of Ki67 protein, but the coloration intensity in positive group is stronger than that in negative group. There was obvious difference in LI among T grade (F=3.819, P<0.05) and LI correlates negatively with the survival time of the patients(rs=-0.403, P<0.001). The labeling index(LI) of Ki67 protein in cancer cells is (41.44+12.29)% in positive group and (19.01 + 12.87)% in negative group. There is a significant difference in Ki67 LI between the two groups(t=7.046, p<0.001).2.2 The expression of Cyclin Dl protein in SCLCNo example expresses Cyclin Dl protein. Conclusion:1. There is the expression of c-Kit protein in SCLC which suggests that the occurrence and evolution of SCLC concerns the overexpression of c-Kit protein nearly. The close relationship between the expression of c-Kit and T stage shows...