The possibility of molecular targeted therapy in patients with pulmonary large cell neuroendocrine carcinoma.

Abstract

e21113 Background: The prognosis for patients with large cell neuroendocrine carcinoma (LCNEC) of the lung is very poor. However, the optimal treatment for patients with LCNEC is not decided. Recently, it is reported that molecular targeted therapy is effective for patients with lung carcinoma. In order to improve the prognosis of patients with LCNEC, it is important for us to understand the possibility of molecular targeted therapy for patients with pulmonary LCNEC. In this study, we studied gene amplification, gene mutation and immunohistochemical expression for molecular markers in patients with pulmonary LCNEC, and compared those with patients with pulmonary adenocarcinoma which has already introduced many kinds of molecular target therapies. Methods: We analyzed 13 patients with primary lung carcinoma diagnosed as LCNEC according to the classification of World Health Organization in 1999 and 14 patients with adenocarcinoma, which underwent treatment at Kitasato University Hospital. We evaluated immunohistochemical expression for CD20, c-KIT, human epidermal growth factor receptor type 2 (HER2), and vascular endothelial growth factor (VEGF), gene mutation for epidermal growth factor receptor (EGFR), K-ras and c-kit, and gene amplification using fluorescence in situ hybridization (FISH) for EGFR. Results: In cases with LCNEC, the expressions of CD20, c-KIT, HER2, and VEGF were 0/13 (0%), 10/13 (76.9%), 4/13 (30.8%), and 13/13 (100%).In c-KIT and HER2, there were significant differences between LCNEC and adenocarcinoma (p = 0.0018, c-KIT, and p = 0.0037, HER2). Only 2 cases with LCNEC had strong expression of HER2, although no case with adenocarcinoma had that. Cases with adenocarcinoma had a significantly higher rate of EGFR gene mutation than LCNEC cases did, although there was only 1 mutation of exon 20 of EGFR gene in LCNEC. There is no mutation of K-ras and c-kit and no amplification of EGFR-FISH in cases with LCNEC. Conclusions: In LCNEC, the expressions of c-KIT and VEGF were frequently observed, however, the gene mutation of c-kit was not done. Anti-VEGF treatment is promising for patients with LCNEC, although the treatment for c-KIT was not clear. No significant financial relationships to disclose.