Abstract

9595 BACKGROUND: Overexpression of receptor-type tyrosine kinase is found in various malignant tumors and may be associated with aggressive biologic potential. The CD117 (c-kit) tyrosine kinase oncoprotein is overexpressed in many tumors including neuroendocrine carcinomas (NEC) of the lung. Our hypothesis is that CD117 overexpression in NEC influences disease outcome. METHODS: Lesions from patients with low, intermediate and high-grade NEC were biopsied or resected from several anatomic sites (lung, GI tract, skin). The tumors were studied for CD117 overexpression. Archival formalin fixed, paraffin-embedded tissue was immunostained with antibodies against CD117, p53 and Ki-67 using the avidin-biotin-peroxidase method. Staining was assessed quantitatively by four observers using a four-tiered (quartile) scoring method. Cases scoring 2+ or greater were considered positive (overexpressed). Survival of patients with high-grade NEC was estimated using the Kaplan-Meier method. RESULTS: Tissue was analyzed from 106 subjects diagnosed between 1997 and 2003 (M:F=42:64, median age 66 years). NE tumors were distributed as follows: 20 low grade (typical carcinoid), 4 intermediate grade (atypical carcinoid) and 82 high grade (76 small cell, 1 large cell NEC, 5 Merkel cell). CD117 overexpression by tumor grade was distributed as follows: low-grade: 0% (0/20), intermediate-grade: 0% (0/4), high-grade: 66% (54/82). Survival analysis was performed on the subjects with high-grade NEC. High-grade NEC were classified as either positive for CD117 overexpression (n=54) or negative (n=28). There were Median survival time showed no significant survival difference between the two groups (P=0.25). CONCLUSION: Our data suggests that CD117 does not overexpress in low and intermediate-grade NE tumors and does overexpress in a high percentage of high-grade NEC. Given our small sample size, the overexpression or lack of expression in high-grade NEC does not appear to affect the aggressiveness of this disease in terms of survival. Also in our study, a high percentage of the high-grade NEC did overexpress CD117 and it is likely that imatinib (Gleevec) may be an effective form of therapy in this patient population. No significant financial relationships to disclose.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.