Ann Thorac Surg 2004;77:252-253
© 2004 The Society of Thoracic Surgeons
Original article: general thoracic
Invited commentary
James S. Allan, MD
Division of Thoracic Surgery, Massachusetts General Hospital, 55 Fruit St, Blake 1570, Boston, MA 02114, USA
e-mail: jallan{at}partners.org
The c-kit gene is a conserved proto-oncogene that codes for a growth factor receptor with tyrosine kinase activity. This 145 kDa receptor is also referred to as the Steel factor receptor, the mast/stem cell factor receptor, and CD117. It is constitutively expressed on pluripotent hematopoietic progenitor cells, melanocytes, and primordial germ cells, where it plays a crucial role in the development of these cells. Mutations of the c-kit gene are responsible for human piebaldism, which is an autosomal dominant pigmentation disorder.
Increased c-kit-mediated tyrosine kinase activity has been observed in a number of human malignancies, including gastrointestinal stromal tumor, seminoma, acute myelogenous leukemia, small-cell lung cancer, and ovarian cancer. In this paper, Casali and colleagues examined the expression of c-kit receptor using a rabbit-anti-human CD117 antibody in 33 large-cell neuroendocrine carcinomas of the lung. They found that 61% of the resected cancers expressed the c-kit protein. More importantly, the investigators observed a significant survival difference between the c-kit positive and c-kit negative patients (3-year survival of 44% vs 82%, respectively), suggesting a causal relationship between c-kit receptor expression and the aggressiveness of these lung cancers.
These data highlight the growing importance of staging malignancies on a molecular basis, as a complement to traditional anatomic staging. These data also support an expanded role for the use of tyrosine kinase inhibitors in the treatment of these lung cancers. At present, excellent clinical results are being achieved in patients with chronic myelogenous leukemia with the use of the tyrosine kinase inhibitor, imatinib (GleevecTM, Novartis). Numerous other related inhibitors are now undergoing clinical trials in the treatment of malignancies with high c-kit expression. Over the next decade, the burgeoning field of molecular oncology is likely to yield a plethora of potent and specific growth inhibitors that will revolutionize the medical management of malignancy and improve long-term survival following surgical intervention.
