Immunohistochemical Prognostic Markers in Intracranial Ependymomas: Systematic Review and Meta-Analysis

Abstract

Distinction between grade II ependymomas and anaplastic ependymomas based on histopathological examination solely is problematic and, therefore, the management of intracranial ependymomas remains controversial. The aim of this study was to conduct a systematic review (SR) and meta-analysis (MA) of data published on immunohistochemical prognostic markers (IPM) in intracranial ependymomas (IE), and to establish an evidence-based perspective on their clinical value. Following the extensive search based on a strictly defined group of key words, 30 studies reporting results on IPM in IE were identified. Due to a pronounced inter-study heterogeneity, only 14 publications fulfilled the criteria for inclusion into SR. From the total of 67 immunohistochemical markers, 18 were found to correlate with prognosis. However, owing to inadequate data publishing, MA could be performed only with data on proliferation marker MIB-1 (Ki-67) from 5 publications, including 337 patients: The pooled hazard ratio for overall survival was 3.16 (95% confidence interval = 1.96-5.09; p < 0.001) implicating that patients suffering from tumors with higher immunohistochemical expression of MIB-1 had a significantly worse outcome. Marked inter-study heterogeneity and incomplete data publishing in primary studies significantly limited extent of the SR, and the possibility of performing MA. Although the prognostic impact of MIB-1 immunoexpression in IE could be confirmed, there remains lack of further reliable IPM that could be used in routine diagnosis. We encourage to search for new, useful markers, as well as to standardize lab-techniques and data interpretation algorithms across laboratories in order to increase data compatibility.

Prognostic relevance of global histone 3 lysine 9 acetylation in ependymal tumors

“…Based on the evidence, MIB-1 labeling index correlates with the grade of malignancy in ependymal tumors. 19,25 We also found that MIB-1 expression has a reverse correlation with H3K9Ac expression in tumors such that tumors with higher MIB-1 expression had lower H3K9Ac levels and vice versa. Concerning ependymal tumors, to the best of our knowledge, there are no previous reports on histone acetylation levels either by the gene candidate approach on specific promoter regions or by analysis of global histone acetylation changes at the cell level.…”

Prognostic marker analysis in pediatric intracranial ependymomas

“…Kaplan-Meier methods were used to estimate median, 1, 2, 3, 5 and 10 year OS and PFS for all patients overall, and within strata defined by Tenascin C, histologic grade and CA IX status (B5/ [5). The log-rank test was used to compare survival distributions between patient subgroups.…”

“…Recent evidence points to loco-specific biologic differences mediating growth [1, 3,4]. For example, site-specific findings such as mitotic activity, vascular proliferation and necrosis are robust markers of prognosis in posterior fossa ependymomas, but not in spinal cord ependymomas [3][4][5][6][7].…”

Estudo das alterações na expressão gênica dos ependimomas

“…Há, também, estudos com marcadores imuno-histoquímicos, porém sem resultados definitivos (Korshunov, Golanov et al 2002;Zamecnik, Snuderl et al 2003;Kuncova, Janda et al 2009;Zawrocki, Izycka-Swieszewska et al 2011). …”

“…A busca por biomarcadores para melhor predizer a evolução clínica dos pacientes com ependimoma tem sido realizada por muitos autores (Gilbertson, Bentley et al 2002;Korshunov, Golanov et al 2002;Preusser, Wolfsberger et al 2005;Mendrzyk, Korshunov et al 2006;Ridley, Rahman et al 2008;Tabori, Wong et al 2008;Kuncova, Janda et al 2009;Korshunov, Witt et al 2010;Milde, Hielscher et al 2012;Modena, Buttarelli et al 2012;Moreno, Popov et al 2013;Mack, Witt et al 2014). Apesar dos ependimomas serem considerados como uma única doença devido às mesmas características histológicas, a maioria dos estudos mostra um perfil de expressão gênica diferente dependendo da localização do tumor e da idade do paciente ao diagnóstico (Hirose, Aldape et al 2001;Dyer, Prebble et al 2002;Taylor, Poppleton et al 2005;Modena, Lualdi et al 2006;Kilday, Rahman et al 2009;Palm, Figarella-Branger et al 2009;Andreiuolo, Puget et al 2010;Johnson, Wright et al 2010;Witt, Mack et al 2011;Nagasawa, Trang et al 2013).…”