Mast Cell Tumors
And
Boxer Dogs
http://www.ncbr.org/assets/img_hp_dogs2.jpg
Mast Cell Tumors
make up the top form of cancer seen in the Boxer dog breed. They make up 25% of the reportable cancers
seen in this breed. Studies have shown
the Boxer breed to be genetically predisposed to these types of cancers. By understanding the genetic background of
these tumors, the scientific community can hope to find better treatments and a
cure for this type of cancer.
Mast cells are
naturally-occurring, specialized cells found in all healthy Boxers. Normal mast cells help the Boxer’s immune
system respond to inflammation and allergy stimuli. When activated normally, they release
histamines, heparin, prostaglandins, and serotonin as a normal body response to
a reaction. Unfortunately for Boxers,
certain parts of these cells can function incorrectly which in turn can cause
excess chemicals to be released and cause mast cell tumors (aka
mastocytomas and mast cell sarcomas).
http://www.vetmed.lsu.edu/oncology/Canine%20Tumors%20II/img005.jpg
Mast Cell Tumors can
be tricky to identify. Obviously, one
sign of these growths is a tumor appearing as a raised, nodular mass. However, these tumors may appear anywhere on
the body, change size on a daily basis, and can be soft or solid even appearing
as normal tissue. Therefore, the only
way to diagnose a mast cell tumor is through a biopsy. Once diagnosed, mast cell tumors are graded
on a scale of 1 to 3.
Grade 1: The cells are well-differentiated, the
only
Treatment that is
needed is the surgical removal
Of
the affected area. The prognosis
looks good!
Grade 2: The cells are moderately differentiated and
Treatment and
prognosis is difficult to predict.
Grade 3: The cells are poorly differentiated and are
Considered very
aggressive at this stage. The
Prognosis is poor.
http://www.vet.uga.edu/vpp/CLERK/Nesbit/Fig1a.jpg
The image above shows well differentiated
mast
cells. Note how these cells have many
cytoplasmic granules.
http://www.vet.uga.edu/vpp/CLERK/Nesbit/Fig2a.jpg
The image above shows poorly
differentiated
mast
cells. Note how these cells have very
few
granules in their cytoplasm.
Current treatment
for mast cell tumors can range depending on the prognosis. As stated above, treatment can be as simple
as surgical removal of the affected tissue.
For Grade 2 and Grade 3 cases you have the added treatments of
radiotherapy, chemotherapy, and prednisolone
therapy. Due to the stress of these
therapies and the nature of these tumors, much research is being put into
looking at the molecular genetics of these cells to find better treatments.
Grade Distribution of Mast
Cell Tumors in Various Dog Breeds
http://www.vetpathology.org/cgi/content-nw/full/39/5/529/T01
What research shows
us today is that for some reason the Boxer breed overall has a high level of
expression of c-kit protooncogene (c-KIT) , which is a stem-cell factor which controls mast cell
growth and differentiation. Not only
were the expression levels high, the Boxer breed seems to also accumulate c-KIT
near the cell nucleus, instead of throughout the cell membrane where it is
usually seen.
With this increased
activity, there are also mutations being seen in the form of duplications,
point mutations, and some small deletions within the juxtamembrane
domain of c-KIT. In fact, there seems to
be a correlation between the duplication mutations increasing the
aggressiveness of the tumors.
http://www.vetpathology.org/cgi/content/full/39/5/529/T03
The chart above shows the
distribution of duplications and deletions in c-KIT across different dog
breeds. Please note that all data came
from at least Grade II Mast Cell Tumors.
One other difference
Boxers affected with mast cell tumors are showing is an increase in frequency
of fragile site expression in the telomeres of the arms of chromosomes 3 and 4
and on the distal half of chromosome 15.
Due to this study, there are experimental drug studies being done on
protein kinase inhibitors affecting these areas. Finalized research standings have not yet
been published on these findings.
In the end, there is
no prevention for mast cell tumors in this beloved breed of dogs. Still, with early detection these tumors can
be controlled in a way so they do not cause as much harm to our pets. This detection begins at home with the
owners. Boxer owners need to be aware of
this danger and look their dogs over on a consistent basis for any types of
growths that may resemble mast cells. At
first sighting, a trip to the Veterinarian should be made for a biopsy, for
this is an issue that is better caught early than late.
BIBLIOGRAPHY:
For More
Information and Support for Research on Mast Cell Tumors in Boxer Dogs:
CanineCancerAwareness.Org. http://www.caninecancerawareness.org/CanineCancerMastCell.html.
This is an informational
website designed for owners of pets dealing with several types of cancer. It contains information on the cancers as
well as traditional and non-traditional therapy plans. This site also provides information on how to
participate in clinical studies.
This link takes you to a
discussion from the
Boxerworld: The Ultimate Boxer
Resource on the Net. Mast Cell Tumor/Alternative Treatments. http://boxerworld.com/forums/showthread.php?p=755684
This is a forum based
website that discusses more non-traditional methods of combating mast cell
tumors in boxers. This entails food
regimes to holistic therapy.
This is a research article
dealing with the pathology of high-grade mast cell tumors. An excellent resource for
dealing with the more complicated scenarios.
Aug. 1991. NCBI. Chromosomal fragile site expression in
dogs: II. Expression in boxer dogs
with mast cell tumors. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1910264&dopt=Citation.
A research article looking
at differences in fragile site expression in boxers with mast cell tumors.
Jan. 1998.
Bellwether: Cancer in Dogs The 28th Annual Canine Symposium. http://www.vet.upenn.edu/schoolresources/communications/publications/bellwether/43/canine.html.
A discussion looking at the
newest theories in treating different types of canine cancer.
Print References:
M. Kiupel, J.D. Webster, J.B. Kaneene, R. Miller, and V. Yuzbasiyan-Gurkan. The Use of KIT and Tryptase Expression
Patterns as Prognostic Tools for Canine Cutaneous
Mast Cell Tumors. Veterinary Pathology.,
This
article discusses different patterns of expression of KIT and
Tryptase on different grades of tumors.
N.K.
Pryer, L/B/ Lee, R. Zadovaskaya,
X. Yu, J. Sukbuntherng, J.M. Cherrington,
and C.A. London. Proof of Target for SU11654: Inhibition
of KIT Phosphorylation in Canine Mast Cell Tumors. Clinical Cancer Research.,
This
article discusses the therapeutic idea of inhibiting c-KIT.
This
article discusses the finding of a group of experimental drugs that aim to
inhibit tyrosine kinase with mast cell tumors.