June 08, 2016

Study Uncovers Breed, Sex Predilections for High-grade Mast Cell Tumors

Researchers from the North Carolina State University College of Veterinary Medicine in Raleigh investigated the association between breed and clinical behavior of the tumor.
By Amy Karon, DVM, MPH
Older dogs, intact males, Staffordshire terriers, and boxers are at greatest risk of developing high-grade cutaneous mast cell tumors, and boxers and other breeds descended from bulldogs are at increased risk of MCTs of all grades, according to a large retrospective study.
 
In contrast, German Shepherds, dachshunds, and poodles are at lowest risk for high-grade cutaneous MCTs, said Hiroyuki Mochizuki, DVM, PhD, of North Carolina State University College of Veterinary Medicine in Raleigh.
 
Cutaneous MCTs are heterogeneous cancers with widely varying clinical outcomes that probably reflect an underlying molecular heterogeneity, according to the researchers. “Despite the well-described breed predisposition to MCTs, little is known about the association between breed and clinical behavior of the tumor,” they wrote.
 
Therefore, they retrospectively reviewed records for 9,375 cutaneous MCTs that were confirmed by histopathology at Antech Diagnostics, a veterinary diagnostics laboratory in the United States, between 2011 and 2013. Each case included complete records of tumor grade based on Patnaik’s 3-tier scheme, breed, sex, neutering status, and age. The researchers also reviewed the grade based on Kiupel’s 2-tier scheme, when possible. Dogs with multiple cutaneous MCTs were scored based on the highest-grade tumor. On average, the dogs were nearly 8 years old, and the cohort included more than 25 different breeds, as well as mixed breeds.
 
Cutaneous MCTs were most often intermediate in grade based on Patnaik’s system (76%), but 16% were low-grade and 8% were high-grade, the investigators reported. Only about 60% of tumors were also graded according to Kiupel’s system, but all specimens that were graded as either low or high in one scheme were graded the same way based on the other system.
 
Male dogs were significantly more likely to have high-grade cutaneous MCTs than females (odds ratio, 1.26; 95% confidence interval, 1.1 to 1.5), the investigators reported. Notably, intact males had nearly double the odds of high-grade tumors compared with castrated males or intact females. “These results were similar when analyzed by Kiupel’s grading,” the researchers noted. The findings suggest that androgens may increase the risk of tumors, or that estrogen may be protective, but those possible associations need further study, they added.
 
The study confirmed predilection for cutaneous MCTs among breeds descended from bulldogs. For example, Staffordshire bull terriers were about eight times more likely to have high-grade cutaneous MCTs compared with purebred dogs as a group (relative risk, 8.1; P less than .001). Other high-risk breeds included American Staffordshire terriers (RR, 4.5; P less than .001) and boxers (RR, 2.7; P less than .001). However, lower-grade cutaneous MCTs also were likely to come from boxers, “resulting in a predominance of low or intermediate-grade MCTs in this breed,” the investigators said. Boxers, bulldogs, French bulldogs, and American Staffordshire terriers, also tended to be diagnosed with MCTs at younger ages – about 6 to 7 years old.
 
Pugs were at relatively high risk for lower-grade cutaneous MCTs, but had about a 75% lower odds of high-grade tumors than other breeds, even after accounting for age, sex, and neutering status (odds ratio, 0.24; 95% confidence interval, 0.15 to 0.37). That finding reflects a previous small study in which only 12% of pugs with cutaneous MCTs died as a result, said the investigators.
 
The analyses also suggested that when Rottweilers and Shih Tzus have cutaneous MCTs, they are likely to be high-grade, but that these breeds are less likely to have cutaneous MCTs in general, the researchers said.
 
Although many pathologists diagnosed and graded the specimens in the study, Patnaik’s and Kiupel’s grading “were highly consistent, indicating minimal impact of inter-observer variation on study results,” the researchers wrote. Overall, the findings support a genetic predilection for high-grade cutaneous MCTs and highlight the need for molecular research into the “etiology of this heterogeneous cancer,” they concluded.
 
The study was partially funded by NCSU Cancer Genomics Fund. The authors had no disclosures.
 
Dr. Amy Karon earned her doctorate in veterinary medicine and master’s degrees in public health and journalism from the University of Wisconsin-Madison. She was an infectious disease epidemiologist and “disease detective” (EIS officer) with the Centers for Disease Control and Prevention before becoming a full-time medical writer. She lives in the San Francisco Bay area, where she volunteers for the local Humane Society.

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