Expression of c-kit (CD117) in neuroendocrine tumours--a target for therapy?
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.
Kostoula
Virginia
V
Department of Medicine, Royal Free Hospital and University of College Medical School, Pond Street, London, NW3 2QG, UK.
Khan
Korsa
K
Savage
Kay
K
Stubbs
Mark
M
Quaglia
Alberto
A
Dhillon
Amar P
AP
Hochhauser
Daniel
D
Caplin
Martyn E
ME
D000255:Adenosine Triphosphate / Q000737:chemistry; D000911:Antibodies, Monoclonal / Q000737:chemistry; D000970:Antineoplastic Agents / Q000494:pharmacology; D001549:Benzamides; D001665:Binding Sites; D000939:Epitopes / Q000737:chemistry; D046152:Gastrointestinal Stromal Tumors / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D007150:Immunohistochemistry; D018358:Neuroendocrine Tumors / Q000378:metabolism* / Q000628:therapy*; D010879:Piperazines / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis*; D011743:Pyrimidines / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D001549:Benzamides; D000939:Epitopes; C000715470:MAS1 protein, human; D010879:Piperazines; D000090063:Proto-Oncogene Mas; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D000255:Adenosine Triphosphate; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit