Vol.:(0123456789) 1 3
J Neurooncol
DOI 10.1007/s11060-017-2606-6
LABORATORY INVESTIGATION
Frequency and clinical signifcance of chromosome 7 and 10
aneuploidies, amplifcation of the EGFR gene, deletion of PTEN
and TP53 genes, and 1p/19q defciency in a sample of adult
patients diagnosed with glioblastoma from Southern Brazil
Dayane B. Koshiyama
1
· Patrícia Trevisan
1
· Carla Graziadio
2
· Rafael F. M. Rosa
1,2,3
· Bibiana Cunegatto
4
·
Juliete Scholl
4
· Valentina O. Provenzi
5
· Alexandre P. de Sá
6
· Fabiano P. Soares
7
· Maíra C. Velho
7
·
Nelson de A. P. Filho
7
· Ceres A. Oliveira
8
· Paulo R. G. Zen
1,2,3
Received: 8 February 2017 / Accepted: 20 August 2017
© Springer Science+Business Media, LLC 2017
145 days. Chromosome 10 monosomy was detected in 52.5%
of the patients, chromosome 7 polysomy in 50%, EGFR
amplifcation in 42.5%, PTEN deletion in 35%, TP53 dele-
tion in 22.5%, 1p deletion in 5% and 19q deletion in 7.5%.
Age was shown to be a prognostic factor, and patients with
lower age presented higher survival (p = 0.042). TP53 and
PTEN deletions had a negative impact on survival (p = 0.011
and p = 0.037, respectively). Our data suggest that TP53 and
PTEN deletions may be associated with a poorer prognosis.
These fndings may have importance over prognosis deter-
mination and choice of the therapy to be administered.
Keywords Glioblastoma · FISH · EGFR · PTEN · TP53 ·
1p19q codeletion · Survival
Introduction
Glioblastoma is the most common and more lethal central
nervous system (CNS) tumor [1]. It occurs in glial cells,
more specifcally in astrocytes, and it is an extremely het-
erogeneous entity, presenting a predominance of poorly dif-
ferentiated, pleomorphic, fusiform or rounded cells [2, 3].
Glioblastoma has an annual incidence of 3–5 cases/100,000
individuals and, despite the diferent therapeutic modalities
available, such as neurosurgery, chemotherapy and radio-
therapy, its prognosis remains poor, with a median survival
of 15 months [4]. In the USA, the estimates for 2015 and
2016 were, respectively, 11,890 and 12,120 new glioblas-
toma cases [5].
In the past years, several cytogenetic and molecular
changes, which may contribute to the diagnosis as well as
the assessment of prognosis and response to treatment, have
been identifed. This diversity should be considered in the
design of the therapy to be ofered to patients, thus selecting
Abstract Glioblastoma stands out as the most frequent
central nervous system neoplasia, presenting a poor prog-
nosis. The aim of this study was to verify the frequency
and clinical signifcance of the aneuploidy of chromosomes
7 and 10, EGFR amplifcation, PTEN and TP53 deletions
and 1p/19q defciency in adult patients diagnosed with glio-
blastoma. The sample consisted of 40 patients treated from
November 2011 to March 2015 at two major neurosurgery
services from Southern Brazil. Molecular cytogenetic analy-
ses of the tumor were performed through fuorescent in situ
hybridization (FISH). The clinical features evaluated con-
sisted of age, sex, tumor location, clinical symptoms, family
history of cancer, type of resection and survival. The mean
age of the patients was 59.3 years (ranged from 41 to 83).
Most of them were males (70%). The median survival was
* Paulo R. G. Zen
paulozen@ufcspa.edu.br
1
Graduate Program in Pathology, Universidade Federal de
Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre,
RS, Brazil
2
Clinical Genetics, UFCSPA and Complexo Hospitalar Santa
Casa de Porto Alegre (CHSCPA), Porto Alegre, RS, Brazil
3
Graduate Program in Biosciences, UFCSPA, Porto Alegre,
RS, Brazil
4
Graduation in Biomedicine, UFCSPA, Porto Alegre, RS,
Brazil
5
Department of Pathology, Grupo Hospitalar Conceição
(GHC), Porto Alegre, RS, Brazil
6
Graduation in Medicine, UFCSPA, Porto Alegre, RS, Brazil
7
Department of Neurosurgery, Hospital Benefcência
Portuguesa, Porto Alegre, RS, Brazil
8
Institute of Education and Research, Hospital Moinhos de
Vento, Porto Alegre, RS, Brazil