Intense p53 staining is a valuable prognostic indicator for poor prognosis in medulloblastoma/central nervous system primitive neuroectodermal tumors

Department of Radiation Oncology, Indiana University Medical Center, Indianapolis 46202, USA.
Journal of Neuro-Oncology (Impact Factor: 3.07). 04/2001; 52(1):57-62. DOI: 10.1023/A:1010691330670
Source: PubMed


Intense p53 immunostaining may predict for a poor prognosis in central nervous system primitive neuroectodermal tumor of childhood.
Medulloblastoma is a common childhood primary brain tumor. Potential prognostic indicators for patients with local disease are age, extent of resection, and gender. However, none of these are well established. Immunohistologic staining is a potentially useful means to identify high-risk patients. The purpose of this clinical pathologic study was to investigate the prognostic significance of GFAP, synaptophysin, Ki-67, and p53 immunostaining in medulloblastoma/central nervous system primitive neuroectodermal tumors (CNS PNETs.)
The records of 40 patients with CNS PNETs were reviewed. Their surgical specimens were immunostained for p53, glial fibrillary acidic protein (GFAP), synaptophysin, and Ki-67. The p53 specimens were scored blindly for the intensity of staining of nuclei (intense vs weak) and the quantity of cells stained. The Ki-67, GFAP, and synaptophysin specimens were analyzed for quantity of cells stained.
Ten patients' specimens stained intensely for the p53 protein. Eleven had weakly staining nuclei. Nineteen specimens had no staining. The patients with specimens that stained intensely had a statistically significant decreased disease free survival (P = 0.03). Mere presence or quantity of p53 nuclear staining did not correlate with disease free survival. Immunohistochemical staining for Ki-67, GFAP, and synaptophysin did not correlate with disease free survival. Clinical parameters of age, gender, and extent of resection also did not approach statistical significance for disease free survival.
Intense nuclear staining for p53 was the only variable in this clinical pathologic study that reached statistical significance for disease free survival. This suggests that intense staining for p53 may be the most important prognostic indicator for non-metastatic CNS PNETs. p53 Immunostaining with antibodies against p53 in CNS PNETs should be studied in a multi-institutional setting with larger numbers of patients.

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    • "Among the prognostic markers investigated to predict disease recurrence, only four have been confirmed as related to a poor outcome in a reproducible manner: p53, survivin, erbB-2 expression and amplification of myc genes [2]. In detail, p53 immunopositivity is an adverse prognostic marker [2,28] and somatic TP53 mutations are associated with chemo- and radiotherapy resistance [2,29]. A recent study showed that somatic TP53 mutations are enriched almost exclusively among SHH and WNT subgroup and are highly predictive of extremely poor survival in SHH MBL [30]. "
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    ABSTRACT: Extraneural metastases (ENM) rarely occur in medulloblastoma (MBL) patients and only few cases of subcutaneous localizations have been described. ENM indicate an aggressive disease associated with a worse prognosis. The characterization of metastatic tumours might be useful to understand their pathogenesis and to identify the most appropriate therapeutic strategies. We present the case of a child with Large Cell Anaplastic (LC/A) MBL, who developed multiple subcutaneous metastases in the scalp area after a ventriculo-peritoneal shunting procedure. The disease rapidly progressed and the child died despite chemotherapy and primary tumour surgical debulking.We molecularly classified the tumour as a group 3 MBL; in addition, we derived stem-like cells (SLC) from a metastatic lesion. Primary tumour, metastases and SLC were further analysed, particularly focusing on features linked to the cutaneous dissemination. Indeed, molecules involved in angiogenesis, cell invasion and epidermal growth factor signalling resulted highly expressed. The present report describes a very rare case of subcutaneous metastatic MBL. The tumour, metastases and SLC have been clinically, pathologically and molecularly characterized. Our case is an example of multidisciplinary approach aiming to characterize MBL aggressive behaviour.
    BMC Cancer 04/2014; 14(1):262. DOI:10.1186/1471-2407-14-262 · 3.36 Impact Factor
    • "Also, p53 score was significantly lower in PA and grade-II astrocytomas than the high-grade ones (anaplastic astrocytoma, glioblastoma multiforme) similar to results obtained by Matsumoto et al.[11] p53 alteration, also correlated inversely with survival amongst medulloblastoma cases in our study. Similar observations were made by Woodburn et al. and Jaros et al.[2223] Both p53 and Ki67 taken together and individually had significant association with survival in these cases, in the present study. "
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    ABSTRACT: The primary brain tumors are the second most common cause of death due to malignancies in children. This study was done to analyze the histological spectrum of primary brain tumors in children and also to find out the expression of p53 and Ki67 in some of the common pediatric brain tumors. This study was done over a period of 2.5 years. The patients were followed up until 6 months to determine the outcome. We examined H and E sections from 61 pediatric brain tumors and also performed immunohistochemical stains with p53 and Ki67 on 52 of these samples. Of the 61 cases of pediatric brain tumors the commonest were pilocytic astrocytomas and medulloblastomas both constituting 22.9% of total cases, followed by high grade gliomas, that is, anaplastic astrocytoma and glioblastoma taken together (14.7%), diffuse astrocytomas (11.4%), ependymomas (8.1%), and oligodendrogliomas (4.9%). Other cases comprised craniopharyngiomas, astroblastomas, and gangliocytoma. The mean age of presentation was 9.3 years, male children being more commonly affected. Ki67 labeling index (LI) and p53 expression in pilocytic astrocytomas and diffuse astrocytomas were significantly lower than that of high-grade astrocytomas. However, there was no significant difference of expression of these two antigens in pilocytic astrocytomas and diffuse astrocytomas. It was found that Ki67 LI was a better marker for distinguishing between grades of astrocytoma than p53 (P=0.000 and P=0.002, respectively). The survival in cases of pilocytic astrocytomas was far better than high-grade gliomas. However, there was no significant difference in survival between pilocytic astrocytoma and diffuse infiltrating astrocytoma. There was significant positive correlation between expression of p53 and Ki67 LI in cases of medulloblastomas. Both p53 (P=0.002) and Ki67 LI (P=0.000) taken individually correlated well with survival in these cases. Also, Ki67 LI is better predictor of outcome than p53. From this study, it can be concluded that Ki67 and p53 score correlated well with the grade of astrocytoma; however, Ki67 is a better marker for differentiating between the grades of astrocytoma than p53. Also, Ki67 LI is a better prognostic factor than p53 in case of medulloblastomas.
    Indian journal of medical and paediatric oncology 03/2012; 33(1):25-31. DOI:10.4103/0971-5851.96965
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    • "However, p53 is wild type in 92%–99% of human sporadic medulloblastomas (Cogen and McDonald 1996; Portwine et al. 2001) and p53 status is clearly linked to radiation responses in several other tumor types (Schmitt et al. 2002). It has been suggested that increased p53 staining (implying p53 dysfunction) is associated with a poor prognosis, and is more common in anaplastic medulloblastoma, known to have a worse clinical outcome , and p53 inactivation is associated with decreased levels of radiation-induced apoptosis in medulloblastoma cell lines (Dee et al. 1995; Woodburn et al. 2001; Eberhart et al. 2005). Therefore, preclinical trials that include radiation therapy using p53-deficient models of medulloblastoma may generate results inconsistent with the majority of these tumors in humans. "
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    ABSTRACT: Medulloblastomas are brain tumors that arise in the cerebellum of children and contain stem cells in a perivascular niche thought to give rise to recurrence following radiation. We used several mouse models of medulloblastomas in parallel to better understand how the critical cell types in these tumors respond to therapy. In our models, the proliferating cells in the tumor bulk undergo radiation-induced, p53-dependent apoptotic cell death. Activation of Akt signaling via PTEN loss transforms these cells to a nonproliferating extensive nodularity morphology. By contrast, the nestin-expressing perivascular stem cells survive radiation, activate PI3K/Akt pathway, undergo p53-dependent cell cycle arrest, and re-enter the cell cycle at 72 h. Furthermore, the ability of these cells to induce p53 is dependent on the presence of PTEN. These cellular characteristics are similar to human medulloblastomas. Finally, inhibition of Akt signaling sensitizes cells in the perivascular region to radiation-induced apoptosis.
    Genes & Development 03/2008; 22(4):436-48. DOI:10.1101/gad.1627008 · 10.80 Impact Factor
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