Biology of

Brain Cancer
NATALIA MARTINS HOFFMANN

Definition
Brain tumors are in reality a very diffuse
collection of tumors of the central nervous
system.

Each of these tumors has a distinct biology,

prognosis, and therapeutic approach.

Brain Cancer

Significance
Risk of Developing Cancer:
Approximately 0.6 percent of men and
women will be diagnosed with nervous
system cancer .

Brain Cancer

Lifetime

Tumors

of the CNS account for less than

2% of all global malignancies.

Particularly

devastating: often affect

children and young adults. Frequently
lead to mental impairment or death.
http://www.sosrichi.org/

Singularity
Brain Cancer

biology of the brain

difficult treatment

Unique
Organ

is enclosed in a bony canal: little room

for growth; compression and damage.

Many

tumors extensively invade the brain.

Complete surgical removal impossible.

brain

cancer cells are protected behind a

blood-brain barrier. Disruption=edema, poorly
tolerated (few space, lack of lymphatics).

Etiology
The causes of CNS are complex not completely known

Risk factors unclear. medical condictions and

medicines, overweight, power line, mobile phones..
Increase (?)

A small proportion of brain tumours are related to

Hereditary syndromes
Neurofibromatosis
Von

Hippel-Lindau disease (VHL gene)

Tuberous
Li

(NF gene)

sclerosis

Fraumeni syndrome (p53)

Brain Cancer

Gliomas
most common malignant brain tumours (>50%).

Any tumor that arises from the glial - supportive tissue

of the brain.

Glial cells maintainhomeostasis, formmyelin,

support and protection forneuronsandperipheral
nervous.

http://www.ncbi.nlm.nih.gov/books/NBK10869/figure/A53/?report=objectonly

Brain Cancer

Classification according to origin

Non Glial origin (structures out of brain parenchyma)

Meninges

Cranial Nerve

Pituitary

Pineal

Glial origin: Gliomas

Astrocytomas

Oligodendrogliomas

Ependymomas

Mixed (oligoastrocitomas)

Brain Cancer

Brain Cancer and Metastasis

They

brain tumors rarely metastasize.

Brain Cancer

Primary

may widely infiltrate the nervous system.

Metastatic

brain tumors much more common

than primary brain tumors.

Brain

metastases occur in 20% to 40% of

cancer patients.
6

Brain Cancer and Metastasis

common tumors: lung cancer, unknown
primary, breast, melanoma, renal, and colon
cancers.

Prognosis

no greater than 1-5 months.

Approx.

80% of metastases in cerebral

hemisphere, 17% in the cerebellum and 3% in
the brain stem

The

histopathologic features similar to that of

tumor of origin.

Brain Cancer

Most

Primary Brain Cancer

multiforme

Brain Cancer

Glioblastoma

(astrocytoma)
Medulloblastoma
Ependymoma

Glioblastoma multiforme
The

frequent and lethal primary cancer of the CNS

highest grade glioma tumor,

presence

of necrosis and increase of blood vessels

around the tumor

Patient
very

survival at five years less than 5%

resistant to radio and chemotherapy

diffusely

and deeply infiltrates the normal

brain parenchyma

Brain Cancer

most

Glioblastoma multiforme
De

novo tumors: majority of glioblastomas

in persons age 55 and older.

Secondary

glioblastomas, most often

found in patients ages 45 and younger.

typically start as low-grade or mid-grade

astrocytoma

Brain Cancer

The two types of gliobastoma

Glioblastoma multiforme

highly

heterogeneous tumor: includes a

variety of cancer cell types

differentiated stellar morphology (markers:

GFAP and S100)

Small

and rounded undifferentiated cells mixed

with stromal elements

Brain Cancer

Pathology

Medulloblastoma
most common malignant brain
tumor in children

Embryonal

neuroepithelial tumor of the

cerebellum
Express

markers of neuronal and glial

cell lineage (by being embryonal
tumors.)

Approximately

one-third of patients
with MB tumors remain incurable

Spread

through the cerebrospinal fluid

Brain Cancer

The

Ependymomas
from the wall of the
ventricular system

Brain Cancer

Originate
Can

occur along the entire

craniospinal axis.

Occurs

in both in children and

adults
Pathognomonic

symptom: strong
pain in the neck tomor grows
throughout the foramen magnum.

calcifications

Origin and development:

Stem cells

BCPCs:
Ability

Brain cancer propagating cells

Brain Cancer

hypothesis

to self-renew and proliferate

BCPCs

can initiate new tumors in mice with

high efficiency (showing many traits of human
cancer).

Neural

stem cells and BCPCs: defined by the

same surface markers - Nestin and CD133

Isolated

from GBM, MB & ependymoma

1

Development
Brain Cancer

(BCPC)

Ependymal cell

Tumor cells with stem-like properties.

(Trends in Molecular Medicine Vol.15 No.11)

Biomarkers in neuro-oncology
Overcome the limitation in the histopathological
diagnosis.

Prognostic and drog response evaluation

Gliobastoma: promoter methylation of the O6methyguanine methyltransferase (MGMT) gene:

longer length of survival and chemotherapeutic

response.

EGFR

(epidermal growth factor receptor)

overexpression associated with poor survival.

Brain Cancer

Clinical manifestations
First symptoms are usually due to
increased pressure in the brain.

Headaches, seizures, memory loss

and changes in behavior.

Loss in movement or sensation on one side of

the body, language dysfunction and cognitive
impairments.

Depending upon the size and location of

the tumor.

Brain Cancer

21

Treatment
Surgery

Radiation

Chemotherapy early ast. & olig.

Symptoms medication manangement

BIOLOGIC AND TARGETED THERAPIES

specific targeting of BCPCs might potentially be

more effective at treating the entire tumor mass

experimental approaches have targeted

VEGF/VEGF receptors pathway

improved patient survival and quality of life.

Brain Cancer

Thank You!!
Brain Cancer

https://www.youtube.com/watch?v=hXLh3CQa9XE

References
Costas G. Hadjipanayis, Erwin G. Van Meir. Brain cancer propagating cells:
biology, genetics and targeted therapies. Trends in Molecular Medicine
Vol.15 No.11. Elsevier doi:10.1016/j.molmed. 2009.09.003

Pter Molnr. Classification of Primary Brain Tumors: Molecular Aspects.

Availeble on http://cdn.intechopen.com/pdfs-wm/20839.pdf. Accessed in
03/2015

AMERICAN BRAIN TUMOR ASSOCIATION. Glioblastoma and Malignant

Astrocytoma. Availeble on http://www.abta.org/secure/glioblastomabrochure.pdf. Accessed in 03/2015.

RobertWechsler-Reya & Matthew P. Scott. THE DEVELOPMENTAL BIOLOGY

OF BRAIN TUMORS. Annu. Rev. Neurosci. 2001. 24:385428

Konstantina A. Svokos , Bodour Salhia Steven A. Toms, Molecular Biology

of Brain Metastasis. Int. J. Mol. Sci. 2014, 15, 9519-9530;
doi:10.3390/ijms15069519

Raymond W. Ruddon. Cancer biology. 4. ed. Oxford University Press. 2007

Brain Cancer