Expression of c-kit (CD117) in neuroendocrine tumours - a target for therapy?

Abstract

C-kit is a tyrosine kinase receptor which is expressed in a wide variety of tumour cells such as gastrointestinal stromal tumours (GISTs), germ cell tumours, malignant trans-formation of mast cells, breast adenocarcinomas, malignant melanomas and small cell lung cancers. Imatinib mesylate is a tyrosine kinase inhibitor initially developed against the bcr-abl fusion protein of CML, but also shows therapeutic inhibitory activity against c-Kit expressed in GISTs. Treatment of patients with neuroendocrine tumours (NETs) at present is limited. Our aim was to test NETs for c-Kit expression and hence identify patients for the consideration of therapy with imatinib mesylate. NET patient specimens (n=85) were assessed for expression of c-KIT proto-oncogene (CD117) by immunohistochemistry using two antibodies, a polyclonal antibody and a monoclonal. Of the samples 24% stained positive with the polyclonal antibody and 64% with the monoclonal antibody. This study highlights problems related to screening using c-kit antibodies for immunocytochemistry. It is possible that the polyclonal antibody is less specific. Studies need to be performed to determine if c-kit expression by NETs can be translated into therapeutic benefit by agents such as imatinib mesylate.