A Retrospective And Prognostic Analysis Of Pediatrics Central Nervous System Tumors:Evaluation Of EGFR Family Gene Amplification And Overexpression In Embryonal Tumors And Glioblastomas

Objective:Central nervous system (CNS) tumors are the most common solid tumors that occur in children, and the incidence is increasing year by year. However,there were few big-data follow-up analysis published in China. Our research focused on pediatric CNS small cell tumors, which include medulloblastoma (MB), small cell glioblastoma(GB) and PNET. Retrospective analyze the clinical and pathological features of childhood central nervous system (CNS) tumors, and research the protein expressions and gene amplification of epidermal growth factor receptor (EGFR) family members, and discussing the potential roles they might play in the tumorgenesis and the relationship they have with the prognosis.Methods:According to the2007WHO classification of the tumors of the nervous system, a retrospective analysis were performed on children (age≤16years) diagnosed as CNS tumors in the Affiliated Provincial Hospital, Shandong University and Liaocheng People’s hospital from2000to2012. Statistics analysis the relationship of CNS small cell tumors prognosis with pidemiological and clinical treatment datas. The expression gene amplification of EGFR was detected by immunohistochemistry and fluorescence in situ hybridization (FISH). All datas were analyzed by the SPSS16.0software for windows.Results:383cases were diagnosed as CNS tumors in the Affiliated Provincial Hospital, Shandong University and Liaocheng People’s hospital from2000to2012. It accounted for8%of total4,788cases in our hospital during the same period.59cases were removed from the retrospective investigation for the reason such as clinical medical records is not complete, lose patient contact, no clear diagnosis, patients died before the operation.1. There were192males and132females of the total324cases, male children were common except oligodendrocytes tumor.2. The incidence of children increases with age.3. The most common site of tumors were the cerebral hemispheres and cerebellar hemispheres. Spinal cord tumors account for7.41%of all CNS tumors.4. Among the top ten tumors, astrocytomas and embryonal tumors were the most common histological type.71cases of CNS small tumors were diagnosed, including44cases of MB,19cases of small cell GBM and8cases of PNET.1. The surgical resection range of primary central nervous system tumors is divided into total removal and partial resection (tumor is still residual). The prognosis of small cell GBM and PNET with no statistically significant difference of surgical resection, however, the prognosis of MB with total resection was significantly better than the children with partial resection (P<0.0352).2. All the children did not accept chemical drugs. Only38.64%of medulloblastoma,36.84%of small cell glioblastoma and50%of PNET patients accepted radiotherapy. The median survival of all children received radiotherapy period were longer than the patients with no radiotherapy.3. There was no statisitical difference between the ki67expressions of MBs, small cell GB and PNET(P>0.05). The positive staining rate of ki-67of MB, small cell GBM and PNET was94.12%,66.67%and85.71%respectively. The prognosis of tumor with less than50%ki-67-positive rate is better than the positive rate of tumors in50%of cases.4. The EGFR positive IHC expression cases accounted for91.18%,86.67%and71.43%of MB, small cell GBM and PNET respectively, and there was no statistical different between3tumor groups (P=0.0636). The patients with negative expression and lower expression had good prognosis compare with the patients with high expression.5. Dual-color FISH analysis was carried out to evaluate for each tumor the number of signals in each cell related to EGFR and to the centromeric region of chromosome7. The average ratio of EGFR/centromeric region of human chromosome7signals was more than2.0as calculated positive signals in each tumor group. The cells with orange clusters were also determined as positive expression.The EGFR gene was amplified in19out of34MB tumors (55.88%),7from15small cell GBM cases (46.67%) and4cases of8PNET samples (50%) assessed by FISH. The log-rank survival analysis showed that all CNS small cell tumors patients with EGFR FISH positive signals had longer median survival time compared with ones with negative signals.6. The multiple Cox regression analysis showed that EGFR protein overexpression and gene amplification were the negative correlation factor of MBs, small cell GBMs and PNETs, and at the same time, postoperative radiotherapy were the common positive prognosis factor.Conclusion:1. Astrocytic tumors and embryonal tumors are the most common types of CNS tumors in childhood.2. Overexpression of EGFR were negative correlation factor of MBs, small cell GBMs and PNETs, and postoperative radiotherapy were the common positive prognosis factor.3. The same prognostic factors suggesting those three subtypes can be considered as one group in choosing a treatment plan and estimate prognosis4. The more detailed and large-scale follow-up analysis is summoned in China, for the indiidualized diagnosis and treatment of children with provide evidence-based study basis.