Tumours of the Skeletal System

Question 1

OSA accounts what % of primary bone tumours in the dog?

Answer 1

85%

Question 2

What’s the typical signalment of OSA in dogs?

Answer 2

Middle age to older, large breed
but has a small, but clear peak in 18-24month olds

Question 3

What’s the common age for rib OSA?

Answer 3

4.5-5.4 years

Question 4

What’s the distribution of OSA in smaller dogs?

Answer 4

55% of OSA in dogs <15kg = axial
vs. only 5% are axial in large breed dogs

Question 5

What’s the proportion OSA in the appendicular skeleton?

Answer 5

75%

Question 6

What’s the most common place for OSA?

Answer 6

mostly in the thoracic limbs (2x as likely)
more likely in the distal radius/ proximal humerus; equal distribution in the pelvis limbs between proximal/distal tibia and distal femur; proximal femur less common

Question 7

In order of decreasing frequency, rank to following sites for OSA: cranium, mandible, nasal cavity, maxilla, spine, pelvic.

Answer 7

mandible (24%), maxilla (22%), spine (15%), cranium (14%), nasal/paranasal sinus (9%), and pelvic (6%)

Question 8

what’s the likelihood of multiple OSA sites on presentation?

Answer 8

<10%

Question 9

What are some physical risk factors for OSA in dogs?

Answer 9

• weight bearing bone in late-closing physes
• metallic implant, previous facture w/out internal repair, chornic osteomyelitis
• RT, late side effect in <5% of patients
• Plutonium exposure

Question 10

what’s the most common gene mutation in OSA?

Answer 10

Missense point mutation of p53

Question 11

What’s the % of OSA in the appendicular vs axial skeleton that overexpresses p53? how about non-OSA tumours?

Answer 11

84% in appendicular, 56% in axial, and 20% in other non-OSA bone tumours

Question 12

What are some genetic mutations associated with OSA in dogs?

Answer 12

• p53
• PTEN
• retinoblastoma

Question 13

Which breeds have shown to have inheritable OSA?

Answer 13

• Scottish Deerhounds*
• Rotties*
• Greyhounds
• Great Danes
• Saint Bernard
• Irish Wolfhounds*
  *polygenic spectrum of germline risk factors – associated with bone differentiations and growth pathways

Question 14

How does MET promote OSA in dogs?

Answer 14

MET encodes a tyrosine kinase receptor –> ligates with hepatocyte growth factor (HGF) –> mediates multiple cellular function – cell scattering, motility, and proliferation

Question 15

How does IGF-1 promote OSA in dogs?

Answer 15

cellular effects of growth hormone is mediated via IGF-1 –> it induces cell mitogenesis and protection from apoptosis
- IGF-1R activation leads to activation of both the MPK and AKT signaling.
- increased IGF-1R expression is correlated with decreased survival time

Question 16

How does HER2 promote OSA in dogs?

Answer 16

HER2 is also a tyrosine kinase receptor
it can promote cell transformation and growth
- it’s possible that overexpression is a negative prognostic factor

Question 17

How does mTOR promote OSA in dogs?

Answer 17

it’s an evolutionary conserved protein kinase downstream of AKT – central hub for integration of cellular signals
- aberrant signaling contribute to growth, survival, and chemotherapy resistance in multiple tumour types

Question 18

How does Hedgehog and Notch promote OSA in dogs?

Answer 18

Hedgehog and Notch signaling pathways have been linked to growth, survival, and metastasis in various human cancers
- upregulation of Notch signaling might contribute to OSA pathogenesis

Question 19

What’s the % of dogs with pulmonary nodules or bone mets present on x-rays on presentation?

Answer 19

15%, but 90% will die within 1 year with metastatic disease

Question 20

Which locations may carry a less metastatic potential?

Answer 20

ulna, axial skeleton

Question 21

Is OSA influenced by size?

Answer 21

Yes, the genetics associated small breeds likely contributes to the fact that the MST is similar in small breeds that received Sx only vs Sx + chemo