Proliferative index in astrocytic tumours.

The accurate grading of astrocytic tumours is of prime importance because it is critical to the patient management and survival/outcome. Although internationally accepted WHO grading system of CNS tumours is based on histological features of H&E stained sections, yet there are cases where differentiation between grade II and grade III is difficult particularly when the biopsy is small. Proliferative index derived from MIB-1 immunostaining has been found to be useful in the distinction between various grades of malignancy. Formalin-fixed paraffin-embedded surgical specimens from 90 cases of astrocytic tumours, 30 each of low-grade astrocytoma (grade II), anaplastic astrocytoma (grade III), and glioblastoma multiforme (grade IV), were immunostained by standard indirect immunoperoxidase technique using MIB-1 monoclonal antibody. MIB-1 labeling index (MIB-1 LI) was calculated. The mean MIB-1 LI values of astrocytomas, anaplastic astrocytomas and glioblastomas were 1.75 +/- 1.5%, 8.74 +/- 6.2%, and 20.54 +/- 12.2% respectively and there was statistically significant difference between grade II and III (Unpaired "t" test, T value 5.907, p value < 0.001) and grade III and grade IV (T value 4.734, p value < 0.001). The statistical analysis also revealed that the mean MIB-1 LI increased with histological grade of malignancy (One way ANOVA test, p value < 0.001). This investigation further reinforces and corroborates the findings that MIB-1 LI is useful tool in assigning grading to the astrocytic tumours and hence in treatment modalities and should be used routinely.

Neoplasias astrocitárias e correlação com as proteínas p53 mutada e Ki-67 / Astrocytic neoplasms and correlation with mutate p53 and Ki-67 proteins

As neoplasias astrocitárias correspondem a 60 por cento dos tumores do sistema nervoso central, sendo o estudo da biologia molecular um importante passo para a compreensão da gênese e comportamento biológico destas doenças. As proteínas Ki-67, que é um marcador de proliferação celular, e p53, que é o produto do gene supressor de tumor de mesmo nome, são importantes marcadores tumorais. O objetivo deste estudo foi identificar e quantificar as proteínas Ki-67 e produto do gene supressor de tumor TP53 em diferentes graus de malignidade das neoplasias astrocitárias, bem como analisar suas relações com idade e sexo. Foram estudadas por imuno-histoquímica as proteínas Ki-67 e p53 em 47 pacientes com neoplasias astrocitárias ressecadas cirurgicamente, classificadas previamente e revisadas quanto ao grau de malignidade, de acordo com o proposto pela Organização Mundial da Saúde. Os núcleos celulares imunomarcados foram quantificados no programa Imagelab-softium pela razão paramétrica absoluta entre os núcleos de células positivas e o número total de células tumorais, sendo contadas 1000 células. O delineamento utilizado foi transversal não controlado. Para análise estatística as variáveis foram divididas em grupos, que para a Ki-67 foram ausente, <5 por cento e >5 por cento e para a p53 foram ausente (0), <25 por cento (1+), entre 25 e 50 por cento (2+), entre 50 e 75 por cento (3+) e maior que 75 por cento (4+). Ki-67 esteve presente em 37 casos (78,72 por cento) expressando correlação com maior grau de malignidade (p<0,001) . A p53 esteve presente em 14 casos (35,13 por cento) tendo maior correlação com astrocitoma grau IV (p=0,59). Não houve correlação estatisticamente significativa entre p53 e Ki-67, bem com entre estas variáveis, idade e sexo. Concluiu-se que a hipótese de maior presença de Ki-67 e p53 em neoplasias astrocitárias de maior grau de malignidade, com exceção da correlação entre grau III e p53, é corroborada pelos resultados deste estudo.

p53 protein alterations in adult astrocytic tumors and oligodendrogliomas.

BACKGROUND: p53 is a tumor suppressor gene implicated in the genesis of a variety of malignancies including brain tumors. Overexpression of the p53 protein is often used as a surrogate indicator of alterations in the p53 gene. AIMS: In this study, data is presented on p53 protein expression in adult cases (>15 years of age) of astrocytic (n=152) and oligodendroglial (n=28) tumors of all grades. Of the astrocytic tumors, 86% were supratentorial in location while remaining 14% were located infratentorially - 8 in the the cerebellum and 13 in the brainstem. All the oligodendrogliomas were supratentorial. MATERIALS AND METHODS: p53 protein expression was evaluated on formalin-fixed paraffin-embedded sections using streptavidin biotin immunoperoxidase technique after high temperature antigen retrieval. RESULTS: Overall 52% of supratentorial astrocytic tumors showed p53 immunopositivity with no correlation to the histological grade. Thus, 58.8% of diffuse astrocytomas (WHO Grade II), 53.8% of anaplastic astrocytomas (WHO Grade III) and 50% of glioblastomas (WHO Grade IV) were p53 protein positive. In contrast, all the infratentorial tumors were p53 negative except for one brainstem glioblastoma. Similarly, pilocytic astrocytomas were uniformly p53 negative irrespective of the location. Among oligodendroglial tumors, the overall frequency of p53 immunopositivity was lower (only 28%), though a trend of positive correlation with the tumor grade was noted - 25% in Grade II and 31.5% in grade III (anaplastic oligodendroglioma). Interestingly, p53 labeling index (p53 LI) did not correlate with the histopathological grade in both astrocytic and oligodendroglial tumors. CONCLUSIONS: Thus, this study gives an insight into the genetic and hence biological heterogeneity of gliomas, not only between astrocytic tumors vs. oligodendrogliomas but also within astrocytic tumors with regard to their grade and location. With p53 gene therapy trials in progress, this will possibly have future therapeutic implications.