Role of Immunohistochemical Markers p53 and Ki-67 in Grading of Glial Tumours: A Prospective Study

Abstract

Introduction: Gliomas are the tumours of neuroepithelial tissues and are named according to their cell of origin. Squash cytology and sterotactic biopsies with Haematoxylin and Eosin (H&E) staining form the backbone of diagnosis, nevertheless recent advances in Immunohistochemistry (IHC) have revolutionised the way gliomas are diagnosed and graded. Aim: To evaluate expression and correlation of p53 and Ki-67/MIB 1 amongst a series of gliomas diagnosed morphologically according to World Health Organisation (WHO) classification of Central Nervous System (CNS) tumours 2007. Materials and Methods: The present study was a prospective study conducted over a period of 18 months from December 2016 to May 2018 at a tertiary care centre in Uttarakhand, India. The study group comprised all consecutive cases of glial tumours that were clinically diagnosed and histopathologically confirmed as Gliomas during this period. Histopathological sections were made from formalin fixed tissue and stained with H&E and grading was done according to the WHO grading system 2007 for CNS neoplasms. Subsequently, IHC sections were taken on poly L-lysine coated slides and IHC staining of p53 and MIB1 (Ki-67) was performed. The IHC scores were calculated and correlated with histopathological grade. Statistical analysis was done using Statistical Package for the Social Sciences (SPSS) software version 17.0. Results: A total of 40 cases of glial tumours diagnosed on histopatholgy were included in the study. They showed M:F ratio of 1.22:1 with peak age incidence of 21-30 years. Astrocytoma, grade IV was the most frequent diagnosis followed by grade II on H&E. On IHC, grade II diffuse astrocytomas, grade III Anaplastic Astrocytomas (AA), and Glioblastoma Multiforme (GBM) demonstrated a mean p53 positivity of 29.5, 50.83 and 47.66, respectively and a Ki-67 positivity of 32.5, 48.33 and 58.08, respectively. For ependymomas grade I, II and III the mean p53 positivity was 9, 5.26 and 12, respectively and the mean Ki-67 positivity was 2, 7.93 and 40, respectively. Amongst oligodendrogliomas grade II and III showed a p53 positivity of 6 and 8.25 and Ki-67 positivity of 12 and 30.5, respectively. A stronger correlation was found between an increase in histologic grade and proliferation markers. Conclusion: Histologic grade was the most important prognostic factor with respect to patient survival in glial neoplasms. The immunopositivity for p53 and Ki-67 correlated well with histological malignancy grade in all glioma subtypes, but a considerable overlap of proliferative index was observed between different subtypes.

Expression of P53 and Ki-67 in different grades of astrocytomas

“…Most cases of our study were glioblastoma [31.1%], followed by diffuse fibrillary astrocytoma [26.7 %], pilocytic astrocytoma [22.2 %], and the remaining 20% of cases were anaplastic astrocytoma. These findings are in accordance with the data of Singh et al in which glioblastoma multiforme was the most common glial tumor that represented about 30% of cases [1] . Similarly, in research conducted by Abu Seadah et al, glioblastoma represented 36% of the cases [2] .…”

“…In the current work, the p-value for Ki-67 immunostaining of the various grades of astrocytoma was < 0.0005, which was statistically highly significant. This finding matches the studies performed by [1] . Also, Shivaprasad et al found that the Ki-67 LI of low-grade [Grade II] and high-grade [Grade III &IV] astrocytoma differed statistically significantly [4] .…”

“…Glioma neuropathologic grading is based upon St. Anne/Mayo method, which comprises cellular atypia, mitotic count, endothelial proliferation, and/or necrosis [1] . Astrocytic tumors are considered the commonest glial tumors, which represent more than 25% of all CNS tumors and include a diverse group of neoplasms that differs in terms of their location all over the CNS, gender and age distribution, growing biologic behavior, and therapy options [2,3] .…”

“…Mutations in the p53 gene, which modulates anti-proliferative cellular responses are the most frequent changes in high-grade astrocytic gliomas. Ki-67 labelling index [LI] is widely utilized as a cellular proliferative marker in many tumors, like gliomas [1] . Various studies show that Ki-67 and P53 are essential biomarkers for determining astrocytoma's prognostic and predictive results [1] .…”

“…Ki-67 labelling index [LI] is widely utilized as a cellular proliferative marker in many tumors, like gliomas [1] . Various studies show that Ki-67 and P53 are essential biomarkers for determining astrocytoma's prognostic and predictive results [1] .…”