Abstract 5594: Cyclin D1 expression correlates with supratentorial location of ependymomas

Abstract

Abstract Ependymomas are rare central nervous system tumors. Clinical variables are intercorrelated and usually are not able to predict the disease course. Cyclin D1 is an important regulator of cell cycle and its overexpression has been related with several cancers. The prognostic value of increased cyclin D1 expression in ependymomas has not yet been fully established. We aimed to analyze cyclin D1 gene (CCND1) and protein expression in a large series of ependymomas. We initially performed CCND1 expression in 32 cases of ependymomas. We further analyzed cyclin D1 protein expression by immunohistochemistry of a tissue microarray of 149 samples of ependymomas, corresponding to 121 patients (including relapses). Forty patients were under 18 years and 81 patients were adults (mean 27.2 years). There were 61 intracranial and 60 spinal cases, of which 10 tumors were grade I (myxopapillary), 92 grade II and 19 grade III (anaplastic). Gross total resection was achieved in 62% of cases. Relapse was confirmed in 40.4% of cases (mean follow up of 53 months) and tissue samples of the first surgery and the relapse resection were available for 23 patients. Immunohistochemical reactions were analyzed by two observers independently and final labeling indices (LI) were calculated as the percentage of the positively stained nuclei (negative=0, 0-25%=1, 26-50%=2, 51-75%=3, >75%=4, and focal=F) over the intensity (weak=1, moderate=2, strong=3). Higher CCND1 expression levels were observed in anaplastic cases (p<0.0001) with supratentorial localization (p=0.029). Cyclin D1 expression was considered as negative in 12.9% (LI=0), focal in 17%, weak in 23.1% (LI=1, 2 or 3), moderate in 19.7% (LI=4 or 6) and strong in 27.2% (LI=9 or 12). There was a correlation between mRNA and protein expression levels (p=0.017). Additionally, statistically significant correlations between cyclin D1 LI score and clinical variables as age (p=0.001), tumor location (p<0.0001), histological grade (p<0.0001) and relapse (p=0.046) were observed. Stratified analysis demonstrated that cyclin D1 expression was strong in supratentorial tumor location in grade II (8/12, p<0.0001) and grade III (23/26, p=0.002), in children (22/26 p<0.001) and adults (9/12, p<0.0001). However, cyclin D1 expression did not correlated with progression free survival (p=0.107). Multivariate analysis revealed that risk of recurrence was associated with intracranial tumor location (hazard ratio=4.7; p=0.03) and incomplete resection of tumors (hazard ratio = 6.35; p=0.012) in this cohort. Although there were more relapses in patients with gross total resection and strong cyclin D1 expression (p=0.013), no correlation with incomplete resection was observed (p=0.430). Determination of cyclin D1 expression LI could be used to guide treatment in supratentorial cases with gross total resection. Citation Format: Fernanda G. Andrade, Suely K. N. Marie, Hamilton Matushita, Sergio Rosemberg, Sueli M. Oba-Shinjo. Cyclin D1 expression correlates with supratentorial location of ependymomas. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5594. doi:10.1158/1538-7445.AM2014-5594