Ki-67 Expression in Pulmonary Neuroendocrine Tumors
JA Barletta, L Zellos, K Law, D Sugarbaker, S Rodig, LR Chirieac. Brigham and Women's Hospital, Boston, MA
Background: Mitotic count is an important component of the classification of pulmonary neuroendocrine tumors, but it can sometimes be difficult to evaluate. Immunohistochemical staining for Ki-67 is a robust and widely accepted method for evaluating proliferative activity in a variety of tumors; however, the association between Ki-67 and mitotic activity in pulmonary neuroendocrine tumors remains unclear. We evaluated the percentage of Ki-67 positive cells in pulmonary neuroendocrine tumors and investigated the association between the immunohistochemical expression of Ki-67 and the number of mitoses.
Design: We studied 92 pulmonary neuroendocrine tumors that included carcinoid tumorlets (CTs), typical carcinoid tumors (TCs), atypical carcinoid tumors (ACs), and large cell neuroendocrine carcinomas (LCNECs). All H&E slides (median 9, range 2-19) for cases were evaluated for mitotic count/10 hpf and the presence of necrosis. Ki-67 expression by immunohistochemistry (IHC) was assessed by a pathologist on a tissue microarray constructed from representative sections of each tumor. For each case the percentage of Ki-67 positive cells in the area with the highest percentage of positive cells was recorded. Expression of Ki-67 was also evaluated using immunofluorescence by digital image analysis (AQUA) of whole mount histopathologic sections (157 fields assessed for 13 cases).
Results: The mean mitotic count/10 hpf was 0.3 for TCs, 3.7 for ACs, and 21.0 for LCNECs. The mean Ki-67 expression was 1.1% for TCs, 3.6% for ACs, and 18.5% for LCNECs (p=0.007). Ki-67 expression by IHC was highly correlated with the mitotic count (Pearson r =0.77, p<0.0001). Moreover, immunohistochemical assessment of Ki-67 expression by a pathologist was highly correlated with Ki-67 expression assessed by quantitative AQUA image analysis (Pearson r=0.8, p<0.0001).
Conclusions: We found that there are significant differences in Ki-67 expression by IHC between the diagnostic categories of pulmonary neuroendocrine tumors. In addition, we demonstrated that immunohistochemical expression of Ki-67 assessed by a pathologist correlates with Ki-67 expression evaluated by quantitative AQUA image analysis and is highly correlated with the mitotic count in pulmonary neuroendocrine tumors.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 247, Tuesday Afternoon