Can oligodendrocyte transcriptional factor-2 (Olig2) be used as an alternative for 1p/19q co-deletions to distinguish oligodendrogliomas from other glial neoplasms?

Abstract

Aim of the study:
Oligodendrocyte transcriptional factor-2 (Olig2) is an essential marker for oligodendrocytes expression. We aimed to explore the expression of Olig2 in different glial neoplasms and to investigate if diffuse Olig2 expression can replace 1p19q co-deletion for the diagnosis of oligodendroglioma.

Material and methods:
Olig2 was performed on 53 samples of different glial neoplasms using immunohistochemistry (IHC). 1p/19q deletions were investigated using fluorescence in situ hybridization (FISH).

Results:
Olig2 labelling of different glial neoplasms revealed various expressions, in which 26 tumours showed diffuse expression (≥ 60%) and 23 tumours showed partial focal expression (< 50%). Four tumours showed no expression. Of the 26 tumours, 6 oligodendrogliomas had 1p19q co-deletion and the remaining 3 oligodendrogliomas showed no co-deletion. Three non-oligodendroglial tumours were found to have 19q deletion. The FISH of the remaining tumours (14/26) showed no aberrations. There was no significant difference in the final diagnosis by using 1p19q co-deletion test among glial neoplasms with diffuse Olig2 expression (p = 0.248).

Conclusions:
Olig2 marker cannot be used as an alternative diagnostic method for 1p19q co-deletion to distinguish oligodendrogliomas from other glial neoplasms. Although some glial tumours showed diffuse Olig2 expression, 1p19q co-deletion testing is the best diagnostic method.

Full text

1Folia Neuropathologica 2021; 59/4
Original paper
Can oligodendrocyte transcriptional factor-2 (Olig2) be used
as an alternative for 1p/19q co-deletions to distinguish
oligodendrogliomas from other glial neoplasms?
Maher Kurdi1, Heba Alkhatabi2, Nadeem Shafiq Butt3, Hameedah Albayjani4, Hessa Aljhdali5, Fawaz Mohamed1,
Taghreed Alsinani6, Saleh Baeesa7, Eman Almuhaini8, Ayat B. Al-Ghafari9, Sahar Hakamy4, Eyad Faizo10, Basem Bahakeem11
1Department of Pathology, Faculty of Medicine in Rabigh, King Abdulaziz University, Saudi Arabia, 2Department of Medical Laboratory
Technology, Faculty of Applied Medical Science, King Abdulaziz University, Jeddah, Saudi Arabia, 3Department of Family and Community
Medicine, Faculty of Medicine in Rabigh, King Abdulaziz University, Saudi Arabia, 4Center of Excellence in Genomic Research, King
Abdulaziz University, Jeddah, Saudi Arabia, 5Department of Pathology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia,
6Department of Surgery, King Fahad General Hospital, Jeddah, Saudi Arabia, 7Division of Neurosurgery, Faculty of Medicine, King Abdulaziz
University, Jeddah, Saudi Arabia, 8Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia,
9Cancer and Mutagenesis Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia, 10Department
of Neurosurgery, Tabuk University, Tabuk, Saudi Arabia, 11Faculty of Medicine, Umm-Alqura University, Makkah, Saudi Arabia
Folia Neuropathol 2021; 59 (4): 1-9 DOI: https://doi.org/10.5114/fn.2021.112562
Abstract
Aim of the study: Oligodendrocyte transcriptional factor-2 (Olig2) is an essential marker for oligodendrocytes
expression. We aimed to explore the expression of Olig2 in different glial neoplasms and to investigate if diffuse
Olig2 expression can replace 1p19q co-deletion for the diagnosis of oligodendroglioma.
Material and methods: Olig2 was performed on 53 samples of different glial neoplasms using immunohistochemis-
try (IHC). 1p/19q deletions were investigated using fluorescence in situ hybridization (FISH).
Results: Olig2 labelling of different glial neoplasms revealed various expressions, in which 26 tumours showed
diffuse expression (≥ 60%) and 23 tumours showed partial focal expression (< 50%). Four tumours showed no
expression. Of the 26 tumours, 6 oligodendrogliomas had 1p19q co-deletion and the remaining 3 oligodendro-
gliomas showed no co-deletion. Three non-oligodendroglial tumours were found to have 19q deletion. The FISH
of the remaining tumours (14/26) showed no aberrations. There was no significant difference in the final diagnosis
by using 1p19q co-deletion test among glial neoplasms with diffuse Olig2 expression (p = 0.248).
Conclusions: Olig2 marker cannot be used as an alternative diagnostic method for 1p19q co-deletion to distinguish
oligodendrogliomas from other glial neoplasms. Although some glial tumours showed diffuse Olig2 expression,
1p19q co-deletion testing is the best diagnostic method.
Key words: gliomas, oligodendroglioma, Olig2, FISH, 1p19q co-deletion.
Communicating author
Maher Kurdi, Department of Pathology, Faculty of Medicine in Rabigh, King Abdulaziz University, Saudi Arabia,
e-mail: ahkurdi@kau.edu.sa

2Folia Neuropathologica 2021; 59/4
Maher Kurdi, Heba Alkhatabi, Nadeem Shafiq Butt, Hameedah Albayjani, Hessa Aljhdali, Fawaz Mohamed, Taghreed Alsinani, Saleh Baeesa,
Eman Almuhaini, Ayat B. Al-Ghafari, Sahar Hakamy, Eyad Faizo, Basem Bahakeem
Introduction
The most common primary brain tumours are
those with aglial cell origin, which cannot be fully
classified by cellular morphology only [12]. The mo-
lecular analysis became crucial for glioma differ-
entiation, grading and prognosis. Loss of hetero-
zygosity (LOH) at specific chromosomes is critical
for tumorigenesis and possible transformation of
low-grade gliomas to higher grade gliomas [10].
One of these common genetic biomarkers is 1p19q
co-deletion. This genetic alteration results from the
combined deletion of entire 1p19q after unbalanced
translocation between chromosomes 1 and 19
[t(1:19)(q10;p10)] [8]. Although there are currently
no available molecular markers that reliably distin-
guish oligodendroglial tumours from astrocytomas,
1p19 co-deletion has been considered as one of the
hallmark criteria for the diagnosis of oligodendro-
glioma, based on the 2016 World Health Organiza-
tion (WHO) Classification of Tumours of the Central
Nervous System (CNS) [1,8,10]. Hence, recent clin-
ical trials have approved the associations between
1p19q co-deletion and prolonged overall survival
of patients treated with radiation with or without
chemotherapy [3,4]. One of the limitations of FISH
technique is that it can detect deletions at a par-
ticular locus but cannot assess the extent of these
deletions (partial or full arm). This alteration recently
was found in association with Isocitrate dehydroge-
nase-1 (IDH1) mutation; acommon criterion to diag-
nose oligodendroglioma. However, IDH1 mutation
can be seen in other subsets of astrocytomas [17].
Although partial loss of one or other chromo-
somes have been described in astrocytomas, such as
LOH on 19q for anaplastic astrocytoma and secondary
glioblastoma, the co-deletion has also been report-
ed in some cases of astrocytoma [14,15]. Around
4-12% of primary glioblastomas were also proven
to have 1p19q co-deletion [17]. Kaneshiro et al.
found that 3% of 337 glioblastomas demonstrated
evidence for 1p19q co-deletion [9]. This finding has
never been discussed further in the literature. These
tumours were astrocytic in nature and have shown
features of classical glioblastoma [9]. It was unclear
if those cases were primary glioblastoma or sec-
ondary glioblastoma upgraded from anaplastic oli-
godendroglioma. Another study done by Sim et al.,
who evaluated 80 glioblastomas, has explored
1p/19q co-deletion in only two tumours [16]. Despite
these findings, FISH for 1p/19q co-deletions remains
awidely employed methodology to evaluate gliomas
with oligodendroglial components.
The association of brain gliomas with 1p19q
co-deletion and Olig2 expression has never been
explored. Olig2, amember of the group of basic helix-
loop-helix transcription factors, is essential for the
development of neural progenitors and oligodendro-
cytes [12]. Several studies have detected prominent
Olig2 expression in oligodendrogliomas and oligoas-
trocytomas [2,5-7,11,13]. Many neuropathologists
use Olig2 marker as adiagnostic tool to diagnose oli-
godendroglial neoplasms (oligodendroglioma and oli-
goastrocytoma) when Olig2 is diffusely expressed in
the tumours. However, this association is not proven
yet and requires further investigations.
Lu et al. found that Olig2 was expressed in oligoden-
droglial tumours more than in astrocytic tumours [11].
Nevertheless, Olig2 cannot be used as a distinguish-
ing marker between oligodendroglioma and astrocytic
neoplasms. The expression of Olig2 was proven to be
weak in many glioblastomas except glioblastoma cases
with oligodendroglial component (GBMO), which have
shown prominent Olig2 expression in only oligoden-
droglial foci [7]. This also has been found in pilocytic
astrocytoma cases where oligo nodules are seen [5].
Moreover, Olig2 expression is not merely restricted to
oligodendroglial areas as it was typically expressed in
some grade II astrocytomas.
In this study, we aim to explore the relationship
between Olig2 expression and 1p19q deletion in dif-
ferent glial neoplasms and also to investigate if dif-
fuse Olig2 expression can replace 1p19q co-deletion
for the diagnosis of oligodendroglioma.
Material and methods
Patients selection
This study included 53 patients with different
types of glial neoplasms from one medical institu-
tion in Saudi Arabia. The cases were diagnosed after
complete surgical resection or tumour biopsy. The
study was ethically approved by the National Bio-
medical Ethics Committee at King Abdulaziz Univer-
sity (HA-02-J-008) under general ethical approval.
The clinical data retrieved from the hospital records
included age, gender, tumour type and location, and
recurrence interval (Table I). The histological diag-
nosis was made based on classification of the 2016
WHO [10].

3Folia Neuropathologica 2021; 59/4
Glial neoplasms with diffuse Olig2 expression
Tumour samples
Archival formalin-fixed and paraffin-embedded
(FFPE) tissue blocks of 53 tumours, diagnosed with
different types of glial neoplasms, were utilized in
this study. Haematoxylin and Eosin (H&E)-stained
sections were re-examined by acertified neuropa-
thologist (MK) to assure that the histopathological
diagnosis has been made based on 2016 WHO clas-
sification of CNS tumours.
Methodology
Immunohistochemistry (IHC) for Olig2 and IDH1
antibodies
Protocol
4-μm FFPE tissue sections were used in the IHC
process. The IHC assay was performed on two
types of antibodies (a) anti-IDH1R132H (clone: H09,
rabbit monoclonal antibody, Dianova) and (b) anti-
Olig2 (EPR2673, rabbit monoclonal antibody,
Cat#ab109186, Abcam). The procedure was per-
formed with the ultraView DAB detection Kit on
a BenchMark XT automated stainer from Ventana
(Tucson, AZ, USA). A protocol was established so
that the entire assay procedure consisted of depar-
affinization with EZ Prep at 75°C, heat pre-treatment
in Cell Conditioning medium (Ag unmasking) (CC1;
Ventana) for 60 min and then primary incubation
for 16 min at 37°C. The antibodies were optimized
using different dilutions, range of 1 : 100-1 : 300.
The slides were counterstained with Haematoxylin
II for 16 minutes and bluing reagent was used for
16 min. After that, the slides were removed from
the slide stainer and then immersed into succes-
sive alcohol buffers at different concentrations for
3 min.
Assessment
For Olig2, nuclear and perinuclear staining of
tumour cells was considered apositive expression.
After immunostaining, asingle focal area of positive
expression per patient sample was evaluated under
light microscopy using high-power (40×) magnifi-
cation. The positively stained cells and total cells,
including positively and negatively stained cells,
were counted manually using labelling index based
on the following equation:
Labelling index (%) = [(Olig2+ stained tumour cells)/
(total cells) × 100].
The staining pattern was categorized as (i) dif-
fusely expressed, (ii) partially expressed, (iii) focally
expressed, and (iv) not expressed (Fig. 1A-C, 2A-D)
based on the following scoring system:
Expression Labelling index (%)*
No expression 0
Focal expression > 0-19
Partial expression > 19-59
Diffuse expression ≥ 60
*For statistical analysis, the scores were divided by 100.
Table I. Demographic data of the 53 patients
enrolled in this study. 26 cases were identified
to have diffuse Olig2 expression through immu-
nohistochemistry IHC
Demographic data Total cases
(N = 53)
Cases with
1p19q (n = 26)
Age
Mean (SD) 28.8 (22.9) 36.1 (20.8)
Gender, n (%)
Female 21 (39.6) 12 (46.2)
Male 32 (60.4) 14 (53.8)
Tumour location, n (%)
Frontal 13 (24.5) 12 (46.2)
Parietal 10 (18.9) 6 (23.1)
Temporal 10 (18.9) 6 (23.1)
Occipital 2 (3.8) 1 (3.8)
Lateral ventricle 1 (1.9) 0 (0.0)
Posterior fossa 15 (28.3) 3 (11.5)
Brainstem 1 (1.9) 0 (0.0)
Thalamic 1 (1.9) 0 (0.0)
Histopathological diagnosis, n (%)
Pilocytic astrocytoma 3 (5.7) 2 (7.7)
Pleomorphic
xanthoastrocytoma
2 (3.8) 2 (7.7)
Diffuse astrocytoma 5 (9.4) 1 (3.8)
Oligodendroglioma 9 (17.0) 9 (34.6)
Oligoastrocytoma 1 (1.9) 1 (3.8)
Anaplastic astrocytoma 5 (9.4) 5 (19.2)
Glioblastoma 11 (18.9) 6 (23.1)
Ependymoma 17 (32.1) 0 (0.0)
Olig2 Labelling Index, n (%)
Diffuse expression 26 (49.1) 26 (100)
Partial expression 12 (22.6)
Focal expression 11 (20.8)
No expression 4 (7.5)

4Folia Neuropathologica 2021; 59/4
Maher Kurdi, Heba Alkhatabi, Nadeem Shafiq Butt, Hameedah Albayjani, Hessa Aljhdali, Fawaz Mohamed, Taghreed Alsinani, Saleh Baeesa,
Eman Almuhaini, Ayat B. Al-Ghafari, Sahar Hakamy, Eyad Faizo, Basem Bahakeem
Tumour cases (n = 26) with diffuse Olig2 expres-
sion have been tested for IDH1R132H mutation. Sec-
tions in which > 10% of glial tumour cells positively
stained were defined as IDH1mutant (Fig. 2E, F).
Fluorescent in situ hybridization (FISH) technique
Fluorescent in situ hybridization (FISH) was used
for the detection of deletions involving the human
chromosomal region 1p36 as well as chromosomal
Fig. 1. Olig2 expression using immunohistochemistry (IHC). A) Diffuse expression, B) partial expression,
C) focal expression. Magnification 40×.
A B C
Fig. 2. Olig2 expression and IDH1 mutation in different types of gliomas. A) Partial Olig2 expression in pilo-
cytic astrocytoma, B) diffuse Olig2 expression in glioblastoma, C) diffuse Olig2 expression in pleomorphic
xanthoastrocytoma, D) focal Olig2 expression in glioblastoma, E) IDH1mutant glioblastoma, F) IDH1wildtype
glioblastoma. Magnification 40×.
A B C
D E F

5Folia Neuropathologica 2021; 59/4
Glial neoplasms with diffuse Olig2 expression
region 19q13 on FFPE tissue slides of the 26 tumour
cases that showed diffuse expression by Olig2.
Protocol
A5-μm-thick FFPE tissue on positive charge slides
was deparaffinised according to the instructions of
the ZytoLight FISH-Tissue Implementation Kit (Zyto-
Vision, Bremerhaven, Germany). This process was
followed with digestion by pepsin to allow for probe
hybridization. Then DNA was denatured by heating
and the hybridization was performed using 10 µl
of the probe onto each pretreated specimen. The
used probe (ZytoLight SPEC 19q13/19p13 Dual Color
Probe) appears with orange signals at 1p36 loci and
the control locus 1q25 appears with red signals, the
other probe target 19q13 locus with orange signals
and the control locus 19p133 appears green. Target
DNA and probes were codenatured at 74°C for 5 min-
utes and incubated at 37°C overnight in ahumidified
hybridization chamber (ThermoBrite, Abbott Molecu-
lar Inc.). Post-hybridization washing was performed
to remove excess unbound probes. At the end, the
slides were counterstained with DAPI (4′,6-diamidi-
no-2-phenylindole) for cellular visualization.
Assessment
Enumeration of 1p/19q signals was conduct-
ed by two technologists independently. Scoring of
100 non-overlapping nuclei within the target areas
(100 total tumour cell nuclei) for each probe set
was performed using a Metasystem station (Zeiss
MetaSystems, Thornwood, NY, USA) equipped with
an appropriate excitation emission filter. Results
were reported as the ratio of the total number of
orange signals to green signals for each probe set
(1p36:1q25 and 19q13.3:19p13 signals) (Fig. 3).
Statistical methods
Data are described as frequencies and percent-
ages. Chi-square and Fisher’s exact were used to
Fig. 3. FISH for 1p and 19q deletion using two probes in two different slides and normal control. The used
probe (ZytoLight SPEC 19q13/19p13 Dual Color Probe) appears with orange signals at 1p36 loci and the
control locus 1q25 appears with red signals, the other probe target 19q13 locus with orange signals and
the control locus 19p133 appears green. “Green” signal is normal and “Red” signal is abnormal. A) 1p1q
normal control, B) 19q19p normal control, C) 1p deletion, D) 19q deletion.
AB
CD

6Folia Neuropathologica 2021; 59/4
Maher Kurdi, Heba Alkhatabi, Nadeem Shafiq Butt, Hameedah Albayjani, Hessa Aljhdali, Fawaz Mohamed, Taghreed Alsinani, Saleh Baeesa,
Eman Almuhaini, Ayat B. Al-Ghafari, Sahar Hakamy, Eyad Faizo, Basem Bahakeem
explore the association of between IDH1 mutation
and the type of glial neoplasms. The McNemar χ2 test
was used to explore the diagnostic accuracy be-
tween oligodendroglial and non-oligodendroglial
neoplasms using FISH technique or IHC. All statis-
tical analyses were performed using the IBM SPSS1
ver. 24 statistical software programs (SPSS Inc.,
Chicago, IL, USA).
Results
This study included 53 patients diagnosed with
different types of glial neoplasms (oligodendroglial
and non-oligodendroglial tumours). The mean age
was 28 years; 32 males (60.4%) and 21 females
(39.6%). Patients aged less than 18 years were
19 cases. The type of glial neoplasms and their
locations are summarized in Table I. Olig2 immuno-
labelling of different glial neoplasms have revealed
various staining expressions, in which 26 tumours
have shown diffuse Olig2 expression (≥ 60%) while
23 tumours have shown partial or focal expression
(< 50%). Four tumours have shown no Olig2 expres-
Table II. Demographic information of the 26 patients who showed diffuse Olig2 expression ≥ 60%. The dif-
ferentiation includes histogenesis, IDH1 mutation, and 1p19q fluorescence in situ hybridization (FISH) testing
Histopathological diagnosis Grading Olig2 LI (%) IDH1 status FISH
Oligoastrocytoma Grade III 99 IDH-wildtype 19q deletion
Pleomorphic xanthoastrocytoma Grade II 97 IDH-wildtype Intact
Glioblastoma Grade IV 96 IDH-mutant Intact
Anaplastic astrocytoma Grade III 94 IDH-wildtype 19q deletion
Oligodendroglioma Grade III 94 IDH-mutant 1p19q co-deletion
Oligodendroglioma Grade III 93 IDH-mutant 1p19q co-deletion
Glioblastoma Grade IV 93 IDH-mutant Intact
Glioblastoma Grade IV 92 IDH-wildtype Intact
Glioblastoma Grade IV 92 IDH-wildtype Intact
Oligodendroglioma Grade III 91 IDH-mutant 1p19q co-deletion
Oligodendroglioma Grade III 90 IDH-mutant Intact
Oligodendroglioma Grade III 90 IDH-mutant 1p19q co-deletion
Diffuse astrocytoma Grade II 87 IDH-mutant Intact
Anaplastic astrocytoma Grade III 86 IDH-wildtype Intact
Pilocytic astrocytoma Grade I 85 IDH-wildtype Intact
Anaplastic astrocytoma Grade II 83 IDH-mutant 19q deletion
Oligodendroglioma Grade III 83 IDH-mutant Intact
Anaplastic astrocytoma Grade III 81 IDH-mutant Intact
Pleomorphic Xanthoastrocytoma Grade III 80 IDH-wildtype Intact
Anaplastic astrocytoma Grade III 80 IDH-wildtype Intact
Glioblastoma Grade IV 79 IDH-wildtype Intact
Pilocytic astrocytoma Grade I 77 IDH-wildtype Intact
Oligodendroglioma Grade I 65 IDH-mutant 1p19q co-deletion
Glioblastoma Grade IV 63 IDH-mutant Intact
Oligodendroglioma Grade III 63 IDH-mutant 1p19q co-deletion
Oligodendroglioma Grade III 60 IDH-mutant Intact
LI – labelling index, FISH – fluorescence in situ hybridization
Table III. Fluorescence in situ hybridization
(FISH) testing for the 26 tumour cases that
showed diffuse Olig2 expression
1p19q cases (n = 26)
FISH result
No deletion 17 (65.4%)
19q deletion 3 (11.5%)
1p19q co-deletion 6 (23.1%)
1p19q Co-deletion
No 20 (76.9%)
Yes 6 (23.1%)

7Folia Neuropathologica 2021; 59/4
Glial neoplasms with diffuse Olig2 expression
sion (Table I). Tumours that showed diffuse Olig2
expression of ≥ 60% were tested for IDH1 mutation
and 1p19q co-deletion using FISH (Tables II, III).
Of the 26 tumours, 6 oligodendrogliomas had
1p19q co-deletion and the remaining three oligo-
dendrogliomas showed unremarkable FISH results
(Table II). However, all the 9 cases of oligodendro-
gliomas were IDH1mutant. Additionally, 3 tumours
were found to have 19q deletion: 2 anaplastic
astrocytomas and 1 oligoastrocytoma. The FISH of
the remaining tumours (14/26) did not detect any
chromosomal deletion or gain (Tables II, III). There
was no significant difference in the final diag-
nosis among glial neoplasms with diffuse Olig2
expression by using FISH 1p19q co-deletion test
(p = 0.248) (Table IV). It clarifies that diffuse expres-
sion of Olig2 cannot be solely used to distinguish
oligodendroglioma from other glial neoplasms. Fur-
thermore, IDH1 mutation cannot be also used as an
additional marker to Olig2 expression to diagnose
oligodendroglial neoplasms without 1p19q co-de-
letion (Table V). FISH for 1p19q co-deletion has
revealed 100% diagnostic sensitivity, 85% specificity
and 88.5% accuracy (Table VI).
Discussion
Since Olig2 is an essential marker for the devel-
opment of neuronal progenitor, it is used to express
oligodendrocytes in CNS. It has also been used for
along time as amarker to distinguish oligodendro-
glioma from astrocytoma. This diagnostic method is
currently proven wrong. Several studies found that
Olig2 is highly expressed in different types of glial
neoplasms such as glioblastomas and astrocytomas
[6]. Around 4-12% of glioblastomas were also prov-
en to have 1p19q co-deletion [17]. Astudy done by
Mizoguchi et al. detected rare cases of glioblastoma
with 1p19q co-deletion and high Olig2 expression
[13]. Although 1p19q co-deletion is the most com-
mon genetic alteration found in oligodendrogliomas,
its association with IDH1 mutation was commonly
Table IV. Relationship between glial neoplasms and 1p19q co-deletion in tumours with diffuse Olig2
expression (≥ 60%)
FISH result Tumour with diffuse Olig2 expression ≥ 60% Total p-value
Oligodendroglioma Non-oligodendroglioma
1p19q codeletion 6 0 6 0.248*
No 1p19q codeletion 3 17 20
Total 9 17 26
*McNemar χ2 test with continuity correction
Table V. IDH1 mutation in glial neoplasm with diffuse Olig2 expression (≥ 60%)
IDH status Oligodendroglioma Non-oligodendroglioma Total p-valuea
IDH1mutant 6 (100.0) 9 (45.0) 15 (57.7) 0.065
IDH1wildtype 0 (0.0) 11 (55.0) 11 (42.3)
aFisher’s exact test
Table VI. The diagnostic accuracy of FISH 1p19q co-deletion superior to diffuse Olig2 expression (≥ 60%)
in the diagnosis of oligodendroglioma
Diagnostic decision 95% Confidence interval
Estimate (%) Lower (%) Upper (%)
True prevalence 23.1 9.0 43.6
Test sensitivity 100.0 54.1 100.0
Test specificity 85.0 62.1 96.8
Diagnostic accuracy 88.5 69.8 97.6
Positive predictive value 66.7 29.9 92.5
Negative predictive value 100.0 80.5 100
Proportion of false positives 15.0 3.2 37.9
Proportion of false negative 0.0 0.0 45.9

8Folia Neuropathologica 2021; 59/4
Maher Kurdi, Heba Alkhatabi, Nadeem Shafiq Butt, Hameedah Albayjani, Hessa Aljhdali, Fawaz Mohamed, Taghreed Alsinani, Saleh Baeesa,
Eman Almuhaini, Ayat B. Al-Ghafari, Sahar Hakamy, Eyad Faizo, Basem Bahakeem
explored. This association has never been correlated
with Olig2 expression in different glial neoplasms.
Less than 50% of Olig2 expression in glial neo-
plasms are considered normal as the oligoden-
drocytes distribute normally in the neuropil and
they may infiltrate into the tumours. Glial tumours
with ≥ 60% Olig2 expression warrant what type
of cellular lineage the tumour may have. Currently,
some neuropathologists use Olig2 as a biomarker
to distinguish oligodendroglioma from other glial
tumours. In our study, we have proven this diagnos-
tic manner was wrong. We found that there was no
significant difference in the final diagnosis among
all glial neoplasms with diffuse Olig2 expression
(≥ 60%) by using FISH test. This clarifies that diffuse
Olig2 expression is not an optimum and standard
method to distinguish oligodendroglioma from oth-
er tumours. However, FISH for 1p19q co-deletion
remains the best diagnostic test for oligodendrogli-
oma, regardless of Olig2 expression as it has shown
88.5% diagnostic accuracy. Although FISH can detect
other chromosomal deletions at aparticular locus it
cannot assess the extent of these deletions (partial
or full arm). In contrast, FISH can detect partial 1p
and/or 19q LOH that are commonly found in astro-
cytic tumours.
Some glioblastomas have also demonstrated evi-
dence for 1p19q co-deletion [9,16]. It was unclear if
those cases were primary glioblastomas or second-
ary glioblastomas upgraded from anaplastic oligo-
dendrogliomas. The expression of Olig2 was proven
to be weak in these cases except glioblastomas with
oligodendroglial component (GBMO), which showed
prominent Olig2 expression in only oligodendrogli-
al foci [5,7]. Despite these findings, FISH for 1p19q
co-deletions remains a widely employed method-
ology in evaluating gliomas with oligodendroglial
components. In our study, in 26 out of 34 tumours
that showed diffuse Olig2 expression, the 1p19q co-
deletion was only found in oligodendrogliomas. The
remaining cases were not distinguished by using
Olig2 expression.
Conclusions
Olig2 marker cannot be used as an alternative
diagnostic method for 1p19q co-deletion to dis-
tinguish oligodendrogliomas from other glial neo-
plasms. Although some glial tumours have shown
diffuse Olig2 expression, 1p19q co-deletion testing
is crucial. Furthermore, IDH1 mutation is considered
as an additional marker of 1p19q co-deletion to sup-
port the diagnosis of oligodendroglioma.
Funding
This project was funded by the Deanship of Sci-
entific Research (DSR), at King Abdulaziz University,
Jeddah, Saudi Arabia, under grant no. G: 65-828-
1441.
Ethics approval
The study was ethically approved by the National
Biomedical Ethics Committee at King Abdulaziz Uni-
versity (HA-02-J-008) under general ethical approval.
Availability of data and material
The data that support the findings of this study
are available from the corresponding author (MK)
upon request.
Conflict of interest
The authors report no conflict of interest.
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