A different TRAP220 expression in distinct histologic subtypes of lung adenocarcinoma and the prognostic significance

Abstract

Adenocarcinomas are a very heterogeneous subgroup of lung cancers, in which oncogenesis is linked to different molecular events. Recent evidence suggests that the hormonal status may contribute to the pathogenesis of lung adenocarcinoma. TRAP220 is the main subunit of the TRAP/Mediator complex and it binds to nuclear hormone receptors in the presence of their cognate ligand, as a cofactor of the transcription machinery. Since TRAP220 is an essential coactivator that interacts directly with estrogen receptor β (ERβ), we examined the expression of TRAP220 protein to investigate its role in lung adenocarcinoma, with particular attention being paid to its different histologic subtypes and the ERβ expression. We performed immunohistochemical detection of TRAP220 and ERβ protein in eighty-seven tissue samples from lung adenocarcinoma patients by using a tissue microarray, and Western blotting was then done to confirm the immunohistochemical observations. TRAP220 immunoreactivity was observed in 27 (31.0%) of the 87 adenocarcinoma cases. Analysis of the TRAP220 expression by Western blotting confirmed the immunohistochemical results. The TRAP220 expression was more frequently positive in the non-solid subtypes (bronchioloalveolar, acinar, and papillary patterns) than that in the solid subtype (P=0.027) and the TRAP220 expression was more frequently positive in the well-differentiated adenocarcinomas than that in the moderately or poorly differentiated adenocarcinomas (P=0.005). The tumors with a negative TRAP220 expression were larger in size (P=0.048) and they more frequently showed lymph node metastasis (P=0.002), pleural invasion (P=0.026) and an advanced TNM stage (P=0.012). The frequency of the TRAP220 expression in the cases with an ERβ expression was significantly higher than that in those cases without an ERβ expression (P=0.003). The Kaplan-Meier survival curves demonstrated that the patients with a positive TRAP220 expression had a significantly longer survival time than those patients with a negative TRAP220 expression (P=0.014). The multivariate analysis revealed that a TRAP220 expression was an independent good prognostic factor (P=0.049). Our data may be useful to understand the different biologic basis for the development and progression of the subtypes of lung adenocarcinoma.