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.  11/20/2005. 

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.

 

 

Atlantic Coast Veterinary Conference 2001.  A Systematic Approach to Cancer in Pets:  Clinical Evaluation and Staging.  http://www.vin.com/VINDBPub/SearchPB/Proceedings/PR05000/PR00484.htm  11/20/2005.

This link takes you to a discussion from the Atlantic Coast Veterinary Conference of 2001 on diagnosing mast cell tumors.  This provides an excellent clinical approach.

 

Boxerworld:  The Ultimate Boxer Resource on the Net.  Mast Cell Tumor/Alternative Treatments.  http://boxerworld.com/forums/showthread.php?p=755684  11/20/2005.

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.

 

American College of Veterinary Pathologists.  Mutations in the Juxtamembrane Domain of c-KIT Are Associated with Higher Grade Mast Cell Tumors in Dogs.  http://www.vetpathology.org/cgi/content/full/39/5/529  11/21/2005.

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.  11/21/2005. 

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.  11/21/2005.

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., July 1, 2004; 41 (4) :  371-377.

          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., November 15, 2003; 9 (15) :  5729-5734.

          This article discusses the therapeutic idea of inhibiting c-KIT.

 

C.A. London, A.L. Hannah, R. Zadovoskaya, M.B. Chien, C. Kollias-Baker, M. Rosenberg, S. Downing, G. Post, J. Boucher, N. Shenoy, D.B. Mendel, G. McMahon, and J.M. Cherrington.  Phase I Dose-Escalating Study of SU11654, a Small Molecule Receptor Tyrosine Kinase Inhibitor, in Dogs with Spontaneous Malignancies.  Clinical Cancer Research., July 1, 2003; 9 (7):  2755-2768.

          This article discusses the finding of a group of experimental drugs that aim to inhibit tyrosine kinase with mast cell tumors.