VCO 2019 Flashcards
What is the incidence of c-kit mutation in MCTs?
15% in cutaneous MCT, up to 35% in high-grade tumours
What is the most common c-kit mutation in MCTs?
Internal tandem duplication in exon 11
What is the result of c-kit mutations in MCTs?
All mutations characterized in vitro jave been shown to resultin in constitutive autophosphorylation of the KIT protein i absence of its ligand stem cell factor (SCF)
In the VCO review from 2019 on the prognostic and predictive value of KIT protein ezpression and c-kit gene mutation in canine MCT; what was the 3 main conclusions?
- Prognostic value of c-kit gene mutation- body of evidence to support that ce-kit gene MCTs are more likely to have an aggressive disease as measured by inceased recurrence and decreased survival, but it is not been validated as an independent prognostic factor. It has been predictive for outcome in one study on univariat, but not mulitvariat analysis.
- Increased cytoplasmic KIT localization is associated with worse prognosis as measuered by recurence and survival but it has low positive predictive value an dtherefore should not be used alone. It has more power in using membrande localization to rule out potentially aggressive tumours.
- C-kit mutation status and kit localization may giva an indication of better initial response rate in c-kit mutated tumours, but this may not translate into improvements in long term outcome.
What will membrane KIT localization most likely to identify?
It is most likely to identify tumours that are less likely to behave aggressive.
Marconato et al: Is there a confirmed survival benefit in removal of the regional LN in dogs with cMCT stage 2?
Yes, With a 5.4 times higher risk of tumour progression and 3 times higher risk of tumour related death
Mendez et al: Is there a significant benefit of LN treatment in dogs with high-grade cMCTs?
Yes, prolonged DFS and OS for dogs which had LN treatment.
Grimes et al: Can SNL CT be used for diagnosis of metastatic LNs?
No, there was no correlation between CT findings (enhancement pattern or attenuation) and metastasis.
Which factors were considered important for prognostication of stage 1, high grade MCTs?
Mitotic index and stage in addition to histological grade
What was the MST for dogs with stage 1, high grade MCTs, treated with surgical removal (with or without chemotherapy)?
MST was 1046 days, with a 1 year survival of 80%
What is the MOA of pevonedistat?
NEDD8 activating enzyme inhibitor
Abnormal JAK/STAT activation has been documented in which canine tumours?
- Mast cell tumour
Abnormal JAK/STAT activation has been documented in which canine tumours?
- Mast cell tumour
Name a FNA approved JAK2 inhibitor which has also been trialled in canine MCT cells?
ruxolitinib
Which cellular signalling pathway has been confirmed involved in the development of cutaneous papilloma in dogs?
mTOR
Name a canine tumour with HRAS mutation?
Acanthomatous ameloblastoma
In which canine tumour may intralesional injection of mi-RNA be an alternative treatment option?
Oral melanoma dog, intralesional injection resulted in 8/10 dogs responding. Most had recurrence, with highly variable ST.
What was the MST for dogs with MLO treated with RT with a palliative vs. SRT protocol?
Palliative had MST 5 month - results pulled from a larger study, only 3 cases
SRT- MST 10 months- response was documented in 4/5 dogs. Late effects documented in 3/8 dogs. The response noted was short lived.
What has been defined as a prognostic factor for dermal SCC in dogs?
Acinic change on histopathology
What is the MST for dogs with dermal SCC?
2.5 years - 33 months
Which breeds are overrepresented for dermal SCC in dogs?
Norwegian elk hound, bull terrer, dalmatien, beagle, boxer, basset and pointer
What is the metastatic rate for dermal SCC in dogs?
2-5%
What is a known risk factor for dermal SCC in dogs?
UV
Name a prognostic factor for primary abdominal, visceral sarcomas?
Grade- when graded after the same system used for cutaneous and subcutaneous tumours.
What was the prognostic cut off on MI affecting survival in dogs with visceral sarcoma?
MI less than nine had a better outcome
What is optical coherence tomography?
A diagnostic imaging modality using light waves to generate real time, high-resolution image of tissue at a microscopic level. Aim for it to be sed intra-operatively for visualisation of residual tumour tissue,
What was the sensitivity and specificity for identifying microscopic disease in MCT with optical coherence tomography?
High sensitivity 90% and low specificity 56%- can be used to guide the pathologist to areas of interest, then improve the assucacy in margin assessment.
