Expression of tyrosine kinase receptors in lung carcinoids.
OBJECTIVE
Typical lung carcinoids are usually relatively benign tumors, but distant metastases are seen in up to 12% of the patients. In contrast, atypical carcinoids are more aggressive tumors, displaying metastases in up to 70%. The current treatment of metastatic lung carcinoids is discouraging. New therapies, such as inhibitors of the tyrosine kinase receptor family c-kit, platelet-derived growth factor receptors (PDGFR) alpha and beta and epidermal growth factor receptor (EGFR) have shown promising results in other malignancies and might be of value in malignant lung carcinoids.


METHODS
Tumor tissue from 51 patients with typical lung carcinoids were immunostained with polyclonal antibodies against c-kit, PDGFRalpha, PDGFRbeta and EGFR. Of the 24 patients who had metastatic disease, 17 had distant metastases. Fifteen of the patients had died from their disease.


RESULTS
Twelve of the tumors stained positive for c-kit, 44 expressed PDGFRalpha, 30 showed positive immunoreactivity for PDGFRbeta and 26 were EGFR immunoreactive. Among the 17 patients with distant metastases, 5 tumors expressed c-kit, 12 were PDGFRalpha immunoreactive, 9 stained positive for PDGFRbeta, and 7 showed positive immunoreactivity for EGFR. There was no correlation to distant metastases or survival for c-kit, PDGFRbeta or EGFR.


CONCLUSIONS
Tyrosine kinase receptors such as c-kit, PDGFRalpha, PDGFRbeta and EGFR are expressed in a significant number of patients with metastatic lung carcinoids. Treatment with inhibitors of the tyrosine kinase receptors expressed may be considered.
Granberg
Dan
D
Department of Endocrine Oncology, University Hospital, Uppsala, Sweden. Dan.Granberg@medsci.uu.se
Wilander
Erik
E
Oberg
Kjell
K
D002276:Carcinoid Tumor / Q000175:diagnosis* / Q000556:secondary; D005260:Female; D006801:Humans; D007120:Immunochemistry; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D011379:Prognosis; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis*
D020794:Receptor Protein-Tyrosine Kinases