Significance of Ki-67 Proliferative Index in Midgut Carcinoid Tumors
D Dhall, G Dhall, D Ines, F Chung, A Kim, M Li, SD Colqhoun, J Mirocha, HL Wang. Cedars-Sinai Medical Center, Los Angeles, CA; Childrens Hospital of Los Angeles, Los Angeles, CA
Background: Gastrointestinal carcinoid tumors may show variable clinical behavior despite similar morphology. A high Ki-67 proliferative index has been shown to be associated with metastatic disease and poor survival. A Ki-67 index of 2% is one of the proposed cutoffs for grading carcinoid tumors. Since the clinical behavior is site-specific and most of the metastatic midgut carcinoid tumors have a low proliferative index, the aim of this study was to determine the clinical significance of Ki-67 index in these tumors.
Design: Ki-67 immunohistochemical stain was performed on both primary and metastatic midgut carcinoid tumors from 60 patients. The slides were eyeballed and the area of interest (hot spot in variably stained cases) was circled. Ki-67 index was determined by computer assisted image analysis using Ariol system. The results were correlated with presence or absence of nodal and/or distant metastases, and disease progression defined by increasing size, appearance of new lesions, or worsening symptoms. Spearman rank order correlation and Wilcoxon scores were used for statistical analysis.
Results: There were 32 females and 28 males ranging in age from 29-95 years (mean: 53 years). Fifty patients had metastatic disease, of which 48 had nodal metastasis and 23 had distant metastasis. The mean and median Ki-67 indices were 5.26 (+6.71) and 2.21 for patients with any metastatic disease, and were 1.68 (+1.17) and 1.59 for those without (p=0.044). Similarly, there was a significant difference in the mean and median Ki-67 values for patients with and without distant metastases (7.45+7.77 and 5.0 versus 2.93+4.44 and 2.0; p=0.003). Nine patients developed progressive disease. All of these 9 patients had distant metastases. Among patients with distant metastases (n=23), the median time to progression for patients with Ki-67 index of >10% was 1.9 years versus 12.5 years for patients with Ki-67 of <10% (p=0.0004).
Conclusions: Ki-67 proliferative index in midgut carcinoid tumors has significant correlation with metastatic disease (local or distant). Patients with distant metastases have a significantly higher Ki-67 index than patients without. Patients with distant metastases and a Ki-67 index of >10% are highly likely to undergo clinical progression.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 91, Tuesday Afternoon