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[REV. MED. CLIN. CONDES - 2017; 28(3) 343-351]
SUMMARY
Molecular markers are increasingly being utilized in
diagnosing, prognosticating and predicting response to
therapy of gliomas. The 4th edition of the World Health
Organization (WHO) Classification of Tumours of the
Central Nervous System (CNS) was updated in 2016 and
incorporates multiple molecular markers in combination
with histology to arrive at an integrated pathological
diagnosis (1). Newer entities were defined and some
were removed based on biological and clinical relevance.
Clinical trials have retrospectively incorporated molecular
markers and reported patient outcomes based on them,
which have showed significant survival differences for
specific subtypes of gliomas. Challenges with respect to
interobserver variability in diagnosis based on histology
alone or availability of minimal diagnostic brain tissue
can now be addressed with the use of molecular markers.
Key words: Brain tumor, glioma, molecular markers.
BRIEF OVERVIEW OF CHANGES
The WHO 2016 classification integrated genotypic and
phenotypic parameters that add to diagnostic accuracy of
CNS tumors. This in turn will facilitate more accurate deter-
mination of prognosis and development of targeted treat-
ments. An algorithm beginning with histology and followed
by addition of molecular testing for diagnosing different
subtypes of gliomas has been suggested. Isocitrate dehydro-
genase (IDH ) mutation testing either by immunohistochem-
istry or sequencing will now be part of routine testing and
will classify gliomas as IDH-mutant or -wildtype. As shown
in several studies, IDH-mutant gliomas are generally asso-
ciated with good response to treatment and a better prog-
nosis (2,3). Oligoastrocytoma grade II or III as a diagnosis
has been a subject of high interobserver variability (4,5),
which can now be better designated as either oligodendro-
glioma or astrocytoma with the use of molecular markers
IDH, ATRX, and chromosomes 1p and 19q. However, given
the chance of discordant results and the non-availability of
molecular testing, these diagnostic entities are kept in the
new classification system as oligoastrocytoma and anaplastic
oligoastrocytoma NOS (not otherwise specified), although in
general this diagnosis is being discouraged. The NOS desig-
nation has also been added as a possibility to grades II and
III oligodendrogliomas and astrocytomas and grade IV glio-
blastomas. The use of NOS is to be used in two situations:
if molecular testing has not been performed or if molecular
testing was not conclusive. Gliomatosis cerebri, an entity
that was defined in the original WHO 4th edition from 2007
(6), has now been deleted from the 2016 classification as
it indicates a pattern of spread better defined on imaging.
It is reportedly seen in IDH-mutant astrocytoma and oligo-
dendroglioma as well as IDH-wildtype glioblastoma (7,8).
Two diffuse astrocytoma variants, namely protoplasmic and
fibrillary astrocytomas have also been deleted from the new
CLINICAL RELEVANCE OF MOLECULAR
MARKERS IN GLIOMAS
VARUN MONGA, MBBS (1), KARRA JONES, M.D., PH.D. (2), SUSAN CHANG, MD. (3)
(1) Clinical Assistant Professor. Division of Hematology/Oncology & BMT. Department of Internal Medicine, University of Iowa, Iowa City.
Unites States.
(2) Clinical Assistant Professor, Neuropathology. Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City. Unites States.
(3) Professor in Residence and Vice Chair of Neurological Surgery. Director, Division of Neuro-Oncology. Department of Neurological
Surgery, University of California, San Francisco. United States.
Email:
Artículo recibido: 12-03-2017
Artículo aprobado para publicación: 02-05-2017