Abstract
Context Glioblastoma multiforme (GBM) is a malignant and aggressive primary brain tumor with
a poor prognosis. This adverse prognosis is due to the tumor's tendency for advancement
and recurrence caused by highly intrusive nature of the persisting GBM cells that
actively escape from the main tumor mass into the surrounding normal brain tissue.
On the basis of biomarker illustration, it can be classified into molecular subgroups.
Aims (1) To determine the expression of IDH1, ATRX, p53, and Ki67 by immunohistochemistry,
in a cohort of GBMs. (2) To determine whether altered protein expression of any of
these growth-control genes in GBM will show association with patient survival. (3)
To establish prognostically distinct molecular subgroups of GBM, irrespective of histopathological
diagnosis.
Results In this prospective observational study, 35 histologically diagnosed cases of glioblastoma
were enrolled. The mean age at the time of presentation was 43.46 ± 17.25 years with
a male:female ratio of 1.3:1. Of the 35 cases, microvascular proliferation was seen
in 23 cases. Large foci of necrosis (>50%) were seen in 10 cases and 27 cases had
mitotic count ≥ 5/high power field (HPF). Of 35 cases, 5 (14.3%) cases showed IDH1
immunopositivity and 30 (85.7%) cases were negative for IDH1. ATRX was retained in
24 (68.6%) cases, while it was lost in 11 (31.4%) cases. The p53 immunoexpression
was seen in 31 (88.6%) cases, whereas p53 was negative in 4 (11.4%) cases. The overall
median survival (OS) was 6 months. In two protein pairs, the three compositions were
IDH1–/p53+ (74.3%), ATRX +/IDH1– (62.9%), and ATRX +/p53+ (57.1%). Combined three-protein
immunohistochemical analysis revealed five different molecular variants. Also, 8.6%
(3/35) of the samples had aberrant protein expression of all three proteins, i.e.,
ATRX–/p53 +/IDH1 + , while 11.4% (4/35) were wild-type protein expression group, i.e.,
ATRX +/p53–/IDH1–.
Conclusion In patients with single protein expression, Kaplan–Meier survival analysis showed
statistically better OS in IDH1 mutant glioblastomas. In cases with double protein
pairs, IDH1/p53 revealed statistically significant association with better median
OS. The survival analysis of patients with IDH1/ATRX/p53 protein combinations also
denoted a better OS. Hence, GBM can be grouped into prognostically relevant subgroups
using these protein expression signatures individually, as well as the combined protein
expression signatures.
Keywords
ATRX - glioblastoma - IDH1 - overall survival
