| Part One Clinical factors and prognosis of medulloblastomaObject:To conclude the clinical characteristics of medulloblastoma and to analyze the relationship between clinical factors and survival.Method:The documents of the patients with medulloblastoma who were diagnosed and operated in Huashan Hospital between2002and2008were collected and analyzed. The cohort was screened by the screening criteria. Data went through statistics analysis to describe clinical characteristics. Survival analysis was performed to discuss the relationship between survival time and the clinical factors.Result:36cases were qualified in the cohort, including19children and17adults. The male-to-female ratio was2:1. The majority of tumors (30/36) located in the midline. Most of the cases (28/36) were classic medulloblastoma by histopathological classification. There were no differences between children and adults on tumor location, histopathological type and proliferation index (PI). The average survival time of children was longer than that of adults but without statistical significance. Sex, tumor location, PI, extent of resection did not affect survival time significantly. The survival time of LC/A medulloblastoma was distinct from that of classic medulloblastoma. No differences were observed between other combinations of histopathological types.Conclusion:Children did not differ from adults in gender distribution, tumor location or PI. Age, sex, tumor location, extent of resection or PI did not affect prognosis of medulloblastoma. LC/A indicated worst prognosis of all histopathological types.Part Two Analysis on molecular subtypes and prognosis of medulloblastoma Object:To classify medulloblastoma into molecular subtypes and analyze the relationship between subtypes and survival.Method:Use immunohistochemical staining to detect the expression of GAB1and YAP1in the paraffin-embedded tumor samples in order to classify the cases into molecular subtypes. The clinical features and outcome of different subtypes were analyzed.Result:Non-SHH/WNT subtype (58.3%) composed the majority of the cohort, which was more common in children than in adults. The difference showed no significance. WNT subtype was more common in women cases. The classic type by histopathology prevailed over the three subtypes. Among the cases of classic type,50%were of non-SHH/WNT subtype. All the D/N cases belonged to non-SHH/WNT subtype. There was1case of SHH subtype and2cases of non-SHH/WNT subtype in all three LC/A cases. The distribution of subtypes did not correlate with the level of PI. The order three subtypes according to the length of survival time was WNT, SHH and non-SHH/WNT. The difference between WNT and non-SHH/WNT subtype was statistically significant. Such difference was available in children, male, midline location and classic type cases. However, in adults, female or high PI cases, the survival of subtypes presented without significant difference.Conclusion:The majority of medulloblastoma belonged to non-SHH/WNT subtype which was more commonly seen in children. The distribution of molecular subtypes did not correlate with age, sex, histopathological type or PI. The prognosis of each subtype in an order from favorable to unfavorable was WNT, SHH and non-SHH/WNT.Part Three Expression of Racl and prognosis of medulloblastomaObject:To study the relationship between clinical factors, molecular subtypes and Rac1expression. To evaluate the prognostic value of Rac1.Method:Use immunohistochemical method to detect the expression of Rac1protein in the paraffin-embedded tumor samples. Define Rac1score on the basis of the extent of staining for Rac1. The expression of Rac1and the RS were analyzed under each clinical condition. Survival analysis was performed to assess the outcome with respect to Rac1expression and RS. Result:There were23cases which were positive for Racl staining in the cohort of36cases. RS1and RS2accounted for10cases and13cases, respectively. The expression of Racl revealed no difference between children and adults. The distribution of RS in male and female was similar. All the LC/A cases were of RS2. The number of Racl positive and negative cases was close. Although non-SHH/WNT subtype had the highest proportion of Racl positivity, although the expression was irrelevant to molecular subtype. The cases positive for Rac1(16/22) were common in the high PI group. But neither Racl expression, non RS was relevant to the level of PI. Racl affected overall survival and progress-free survival significantly. The survival of Racl positive case was markedly shortened, regardless of age, sex, tumor location, histopathological type or molecular subtype. In high PI group, Racl expression did not change overall survival. Whether gross-total resection was achieved or not did not affect the survival of Racl negative cases. In contrast, gross-total resection significantly prolonged the survival of Racl positive cases. Of all the cases, the average survival time was negatively correlated with RS. The survivals between RS1cases and RS2cases were of no significance under different clinical circumstances. The overall survival differed from RS0and RS1cases in adults, while progress-free survival remained on the same lever between different molecular subtypes. As for female, survival differed between the cases of RS0and those of RS2.Conclusion:Medulloblastoma presented with Racl positivity indicated poor prognosis. RS could roughly reflect prognosis, which also negatively correlated with survival in adult cases. |
PDF Full Text Request