Expression of c-kit and Cell Cycle Regulators in Non-small Cell Lung Carcinoma

Chang, Sun Hee; Joo, Mee; Kim, Hanseong

Abstract

BACKGROUND: The abnormal expression of c-kit is implicated in the pathogenesis of a variety of solid tumors. The Rb pathway and p53 act as cell cycle regulators. The purpose of this study was to assess the expression of c-kit, Rb, p53, p16 and cyclin D1 and their relationship to clinical and pathological parameters in patients with non-small cell lung carcinomas (NSCLC(s)).
METHODS
Tissue microarrays consisting of 2 mm cores from the corresponding blocks were constructed from 54 NSCLC(s). Immunohistochemical staining for c-kit, Rb, p53, p16 and cyclin D1 was performed. C-kit immunostaining was considered positive if > or =10% of tumor cells were immunoreactive along the membrane and/or in cytoplasm. For Rb, p53, p16 and cyclin D1, tumor cells showing a nuclear staining pattern were interpreted as positive.
RESULTS
We found that c-kit was expressed in 13 (24%) cases, Rb was lost in 39 (72%) cases, p53 was expressed in 28 (52%) cases, p16 was lost in 42 (78%) cases and cyclin D1 was expressed in 33 (61%) cases. The c-kit expression was significantly higher in adenocarcinoma (39%) than in squamous cell carcinoma (8%). We did not find any correlation between c-kit, Rb, p53, p16 and cyclin D1 expression and clinicopathological parameters such as: age, tumor size, lymph node involvement, disease stage and distant metastasis. There was a direct correlation between p53 expression and Rb loss.
CONCLUSIONS
These results suggest that c-kit may be a useful therapeutic target for patients with c-kit positive tumors, and that the disruption of Rb and p53 pathways may play an important role in the development and progression of NSCLC(s).