Cd117 overexpression in neuroendocrine carcinomas

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.