Clinicopathological Characteristics And Molecular Pathological Diagnosis Of RELA Fusion-Positive Ependymoma

Purpose:In 2016,the WHO classification of central nervous system tumors identified RELA fusion gene-positive ependymoma as an independent molecular subtype of ependymoma,with specific morphological characteristics and biological behavior.The purpose of this study was to summarize its clinicopathological characteristics,evaluate the efficiency L1 CAM immunohistochemical exam using FISH test by RELA gene break probes as the gold standard,and explore the prognostic indicators of ependymoma.Method:Clinical and pathological material of 60 cases diagnosed as ependymoma in Guangzhou Sanjiu Brain Hospital and the First Affiliated Hospital of Jinan University from 2012 until now were collected.The paraffin-embedded samples were used for FISH test by RELA gene break probes,and L1 CAM immunohistochemical exam when combined with tissue microarray technology.We summarized the clinicopathological characteristics of this molecular subtype,evaluated the sensitivity and specificity of L1 CAM immunohistochemical exam.We studied the prognostic indicators of ependymoma by Kaplan-Meire method and Cox regression analysis.Result: 1.Compared with RELA fusion-negative ependymoma,there was no significant difference in people composition of RELA fusion-positive ependymoma,60% of them are adults(6/10),located in the supratentorial area(10/10).There was preponderance of males(9/10).50% of this molecular subtype recapitulated the ‘clear cell' and finely branched vasculature characteristic of clear cell morphology(5/10).WHO grade ? accounts for 60%(6/10).We defined overexpressed P53 protein?high Ki-67 index.More cases showed Cyclin D1 positive with higher positive rate in RELA fusion-positive ependymoma.L1 CAM is 100% positive(10/10).2.In ST-RELA-EPN cases,L1 CAM showed strong positive located in membrane.The sensitivity of L1 CAM immunohistochemical examination was 100%,the specificity was 97.9%,and the Youden index was 0.979.3.We obtained survival data of 53 cases.Univariate analysis showed that the progression-free survival of high-grade tumors,age less than 3 years old and subtotal resection was significantly shorter.The overall survival of people younger than 3 years old was shorter than those of other age groups.The overall survival of children younger than 3 years old,people between 3-14 years old,people between 14-40 year-old was significantly prolonged successively.The overall survival of relapsed patients was shortened significantly.Multivariate analysis showed that Ki-67 index,degree of surgery,and radiotherapy were independent prognostic factors for progression-free survival.Only relapse was an independent prognostic factor for overall survival.Conclusion: 1.We did not find a specific prevalence group for RELA fusion gene positive ependymoma.In our study,adults account for more than half of the population.Incidence of clear cell subtype,high histological grade and high Ki-67 index were high.P53 was overexpressed.More cases showed Cyclin D1 positive with high positive rate.L1 CAM was 100% positive.2.The RELA break probe can be used for FISH test.A suitable threshold should be established.RT-PCR test was recommended for controversial cases.3.L1 CAM immunohistochemical exam can be used as an alternative to primary screening because of excellent efficiency.4.Univariate analysis showed that high-grade tumors,young children less than 3 years old,subtotal resection were related to short progression-free survival;low-age group,recurrence were related to short overall survival.Multivariate analysis shows that high Ki-67 index and subtotal resection were risk factors for progression-free survival,and radiotherapy was a protective factor for progression-free survival.Only relapse was an independent prognostic factor for overall survival and a risk factor.Both of the analyses hadn't shown that the prognosis of RELA fusion positive ependymoma was worse than other subgroups.