Immunohistochemical expression of markers Ki-67, neun, synaptophysin, p53 and HER2 in medulloblastoma and its correlation with clinicopathological parameters

Abstract

-Medulloblastoma (MB) is the most common malignant brain tumor in childhood. The alterations found include: presence of oncoproteins p53 and HER2, elevated mitotic index, and presence of neuronal differentiation. The aim of this study was to determine the immunohistochemical expression of markers Ki-67, NeuN, synaptophysin, HER2 and p53 in 40 MB samples and their correlation with clinicopathologic parameters and survival. In 29 patients (72.5%), ≥20% of cells were positive for Ki-67. Males showed greater ki-67 expression (p=0.02) and smaller survival rates (p=0.002). NeuN and synaptophysin were negative in 16 (40%) and 8 (20%) cases, respectively. P53 was positive in 18 (45%) cases, with 11 (61%) weakly positive and 7 (39%) strongly positive. HER2 was positive in 23 (57.5%) of the samples and did not show statistical association with survival (p=0.07).KEy woRds: medulloblastoma, immunohistochemistry, Ki-67, NeuN, synaptophysin, HER2, p53, survival analysis. expressão imunoistoquímica dos marcadores ki-67, neun, sinaptofisina, p53 e her2 em meduloblastoma e sua correlação com os parâmetros clínico-patológicosResumo -Meduloblastoma (MB) é o tumor maligno encefálico mais freqüente na infância. dentre as alterações encontradas estão: a presença das oncoproteínas p53 e HER2, elevado índice mitótico e presença de diferenciação neuronal. o objetivo deste estudo foi determinar a expressão imunoistoquímica (IMQ) dos marcadores Ki-67, NeuN, sinaptofisina, HER2 e p53 em 40 amostras de MB, correlacionando-as com parâmetros clinicopatológicos e com a sobrevida. Vinte e nove pacientes (72,5%) apresentaram 20% ou mais das células positivas para Ki-67. os pacientes do sexo masculino apresentaram maior expressão do Ki-67 (p=0,02) e também menor sobrevida (p=0,002). NeuN e sinaptofisina foram negativos em 16 (40%) e 8 (20%) casos, respectivamente. P53 foi positivo em 18 (45%) casos, sendo 11 (61%) fracamente positivos e 7 (39%) fortemente positivos. HER2 foi positivo em 23 (57,5%) das amostras e não demonstrou associação estatística com a sobrevida (p=0.07).PAlAVRAs-cHAVE: meduloblastoma, imunoistoquímica, Ki-67, NeuN, sinaptofisina, HER2, p53, sobrevida. Medulloblastoma (MB) is the most common malignant brain tumor in children, accounting for about 20% of all primary tumors of the central nervous system (cNs), with a peak of incidence at 5-7 years-old. These tumors have an aggressive behavior and despite treatment, the 5-year survival rate is 60% 1,2 . For therapeutic and prognostic purposes, patients are divided in groups of high and low risk, according to the staging proposed by chang et al. (1969) 3 , age at the time of diagnosis, and presence of residual tumor 4,5 . A more accurate assessment of risk in children with MB can be done using a combination of clinical, histopathologic, and molecular prognostic factors 4,6,7 .

Expression of Epidermal Growth Factor Receptor and HER-2 in Pediatric Embryonal Brain Tumors

“…Previous studies have demonstrated variable immunohistochemical expression of HER-2 in MBs ranging from 40 to 70% of the cases, which is compatible with our observations [4,9,10]. Although HER-2 expression in MBs was correlated with progressive disease and poor prognosis in some studies [4,10], other investigators have not proved any statistically significant association of HER-2 expression with survival [9].…”

“…Although HER-2 expression in MBs was correlated with progressive disease and poor prognosis in some studies [4,10], other investigators have not proved any statistically significant association of HER-2 expression with survival [9]. In our study, we found no correlation between HER-2 expression and prognosis; nevertheless, the number of patients was small.…”

Immunohistochemical expression of Ki67, EGFR and TRKC and their correlation with prognostic factors in medulloblastoma

“…This seems to be in agreement with literature since TRKC is a biomarker of apoptosis of good prognosis, and Ki67 is biomarker of cellular proliferation and poor prognosis, when presenting high levels (9,10) . We also observed a trend (p = 0.071) to a directly proportional correlation between TRKC and EGFR, so that when the first is increasing the latter increases also, which seems to be an antagonistic effect, since TRKC stimulate the apoptosis and EGFR promotes cell growth.…”

“…We also observed a statistical trend toward Ki67 is inversely correlated with age (p = 0.088), i.e., the higher the age, the lower proliferative rate. This also seems to be in agreement with the literature, since children over 3 years of age are considered at low risk, and, consequently would have lower proliferative rates and better prognosis (Table 3) (10) .…”

“…Other prognostic biomarker have been proposed for medulloblastoma, Ki67 proliferative protein has been extensively studied, besides having a correlation with the prognosis of these lesions, since higher proliferative indices seems to be correlated with poor prognosis (9,10,14) .…”