Canine MCT Flashcards

1
Q

Strefezzi et al. 2012. The value of immunohistochemical expression of BAX in formulating a prognosis for canine cutaneous MCT

BAX expression in 24 canine MCT and relate to grade and prognostic value

BAX expression ___ with higher grade

Animals with high levels of BAX were ____ more likely to die from disease and had ___ post-surgical survival times

A

Increased

4.25x, shorter

BAX expression may be related to aggressiveness of MCT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Prada et al. 2012. Evaluation of COX-2 expression in canine MCT

Cox-2 expression in tumors?

Labelled cells ranged from isolated positive cells thorughout the tumor (8) to localized foci (3) or diffuse labeling >50% of cells (31)

Intensity ranged from weak (4), moderate (16), strong (22) and greatest at the margin of tumor

Intensity of Cox-2 between histological groups?

A

86%

Significantly different

No significant difference noted for percentage of Cox-2 positive cells and for immunoreactivity score

Cox-2 inhibitors may be of value in treatment of MCTs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Pakorny et al. 2012. MRI of canine MCTs

On T2-W, 7/9 MCT were hyperintense to muscle and 2/9 isointense

On T1-W, 8/9 isointense and 1/9 mildly hypointense

Metastatic LNs were larger than contralateral LNs

All LNs were isointense on T1-W and hyperintense on T2-W

All LNs were moderately to strongly contrast enhancing

4/5 metastatic and 2/7 normal LNs had heterogeneous enhancement patterns - not significant

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Caristen et al. 2012. Multicenter prospective trial of hypofractionated RT, toceranib, and prednisone for measurable canine MCT

17 dogs with MCT

ORR? how may achieving CR and PR?

Median time to best response? Median PFI?

Overall MST?

Common toxicity?

A

76.4%, 58.8% and 17.6%

32 days (1 month), 361 days

Not reached

GI and hepatic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

O’Connell et al. 2013. Evaluation of prognostic indicators in dogs with multiple, simultaneously occuring cutaneous MCT: 63 cases

On multivariable analysis, dogs with grade 3 MCTs had?

Dogs treated with vinblastine/lomustine?

MSTs were significantly ___ in dogs with one recored MCT on an extremity?

PFS and MST?

A

Shorter PFS (18.7 versus 2.2 months) and MST (24 vs. 3 months)

16x increased risk of dying

Longer

Not reached

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Beralato et al. 2012. Evaluation of minichromosomes maintenance protein 7 as a prognostic marker in canine cutaneous MCT

Michrosome maintenance proteins (MCMs) are sensitive markers of cellular proliferation and predictors of survival in human malignancies

95 dogs included with 31 dying of MCTs

Cut off value for MCM-7?

MST for MCM-7<0.18?

MCM-7>0.18

In multivariable analysis, MCM7 was signifcantly associated with survival

A

0.18

Not reached at 3668

187 days

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Rodriguez et al. 2012. Immunohistochemical evaluation of AKT protein activation in canine MCT

25 MCTs

Was AKT detected? Phosphorylated AKT?

Correlation between labeling and histologic grade?

A

Detected in all samples, 24/25 expressed phosphorylated form

None

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Teng et al. 2012. Overexpression of P-gp, STAT3, p-STAT3 and KIT in spontaneous canine cutaneous MCT before and after prednisolone treatment

P-gp, STAT3, and KIT are involved in GC resistance

Overall objective response rate on prednisolone? Poorly differentiated or higher stage response rate?

Median time span to reach maximal tumor regression?

Expression of P-gp and STAT3 before treatment?

pSTAT3 and KIT expression post-treatment?

Prednisolone treatment that caused marked reduction was correlated with?

Cytoplasmic KIT staining pattern was correlated with?

A

51.8%, lower

14d, 22 (81.5%) reached maximal regression at 21d

Overexpressed

Reduced

pSTAT3

Lower response rate to prednisolone treatment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Giantin et al. 2012. Expression of MMP, tissue inhibitors of metalloproteinase and vascular endothelial GF in canine MCT

Expression of VEGF-A, MMP, TIMP mRNA with histological grade?

A

VEGF-A and MMP mRNA increased and TIMP decreased with increasing grade

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Schlieben et al. 2012. Differences in the proteome of high-grade versus low-grade canine cutaneous MCT

4 stress response proteins were significantly upregulated in high grade tumors - HSPA9, PDIA3, TCP1A, TCP1E

Proteins assciated with cell motility (WDR1, ACTR3, ANXA6) were increased or decreased (ANXA2, ACTB)

Transferrin was down-regulated - which is usually upregulated in neoplastic cells

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Vascellari et al. 2013. Expression of Ki67, BCL-2, and COX-2 in canine cutaneous MCT: association with grading and prognosis

MI and Ki-67 was significantly associated with grading and survival

No association between BCL-2 protein expression and either grading system or health status was observed

BCL-2 mRNA was higher in grade 2 than grade 1 no differences were detected between low and high-grade MCT

Increased BCL-2 mRNA was associated with increased mortality rate

COX-2 detected in 78% of MCT - no assciation with tumor grade or health status

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Klopfleisch et al. 2012. Transcriptome and proteome analysis of tyrosine kinase inhibitor treated canine MCT cells identifies potentially kit signaling-dependent genes

40% of genes increased mRNA expression - pro-proliferative pathways of B- and T-cell receptors, chemokine receptors, steroid hormone receptors and EPO- RAS and MAP kinase signaling

24 proteins has changed expression levels involved in gene transcription e.g. EIA3, EIA4, TARDBP, protein folding e.g. HSP90, UCHL3, PDIA2 and protection from oxidative stress, GSTT3, SELENBP1

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Mackowiak et al. 2013. E-cadherin in canine MCT: decreased expression and altered subcellular localization in grade 3 tumors

Expression of E-cadherin in grade 3 MCT?

A

Decreased expression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Meyer et al. 2013. All subunits of the IL-2 receptor are expressed by canine cutaneous MCT

What % expressed both subunits of the IL-2R? IL2?

IL-2Rg and IL-2 expression in high grade tumors? IL-2 expression decreased in?

IL-2R may be more relevant for early MCT development and well-differentiated tumors

A

86%, 64%

Decreased, c-KIT mutated tumors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Costa Casagrande et al. 2015. The value of molecular expression of KIT and KIT ligand analysed using real time PCR and IHC as prognostic indicator for canine cutaneous MCT

KIT-I, KIT-II, and KIT-III staining patterns?

Tumor recurrence rates and tumor related deaths association with KIT staining patterns?

A

11%, 61.73%, and 27%

No association

Results suggest correlation between aberrant KIT localization and increased proliferative activity of MCTs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Takeuchi et al. 2013. Validation of the prognostic value of histopathological grading or c-kit mutation in canine cutaneous MCT: a retrospective cohort study

Dogs with Patnaick grade III MCT had significantly ___ OS and PFS compared to grade I or II

Difference between grade I and II and OS, PFS?

Kiupel high grade MCT had significantly ___ PFS and OS

Presence of internal tandem repeat-Exon11 was associated with?

A

Reduced

None

Shorter

Shorter PFS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Donnelly et al. 2015. Evaluation of histological grade and histologically tumor-free margins as predictors of local recurrence in completely excised canine MCT

Which tumors were more likely to recur?

29% had HTFM of <3mm - none recurred

Narrow <3mm histologic margins are likely adequate to prevent LR or low grade tumors

High grade tumors have significant risk of LR regardless of HFTM

A

High grade tgab low grade - 35% vs. 3.9%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Warland et al. 2013. Breed predisposition in canine MCT: a single center experience in the UK

Which breeds were predisposed to MCT development?

Which breeds were underrepresented?

A

Boxers, Labrador Retriever, GR, Stafordshire Bull Terriers

English springer spaniel, GSD, WHWT, CKCS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Gentilini et al. 2015. The use of COLD-PCR, DHPLC and GeneScanning for the highly sensitive detection of c-KIT somatic mutations in canine MCT

Convetional PCR/sequencing showed sensitivity of 50-20%

All novel methods had higher sensitivity allowed reaching as low as 2.5-1.2% of the mutated DNA

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Lejeune et al. 2015. Aggressive local therapy combined with systemic chemotherapy provides long term control in grade II stage 2 canine MCT: 21 cases (1999-2012)

Treated with local therapy and systemic chemotherapy (pred, CCNU, VBL)

Median survival for all dogs?

Median DFI?

Dogs treated with surgery and chemo had ____ survival than those with surgery, RT, chemo

___ patients had local recurrence in RT field

A

1359 days (3.7 years)

2120 days (5.8 years)

shorter

2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Shiomitsu et al. 2016. The radiosensitizing effect of the aurora kinase inhibitors, ENMD-2076, on canine MCT in vitro

ENMD-2076 is aurora kinase inhibitor that has multi-targert TKI properties

mRNA and protein expression of aurora-A and aurora B were evaluated

____ seen in cells treated and affected cell cyle in the ___ phase

Radiosensitization was seen after 3Gy and 6Gy exposured with ENMD-2076 for 48 hr

Expression of __ was increased and was highest 24h post irradiation in cells without ENMD-2076 treatment

A

Dose-dependent cytotoxicity, G2/M phase

caspace-3

Usefulness of treating with aurora kinase inhibitors alone or in connjunction with RT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Clarke et al. 2014. Histologic characteristics and KIT staining pattern of equine cutaneous MCT

What breed was over-represented?

Most tumors were ___ differentiated and __ mitotic rates

Abberant KIT staining pattern?

KIT staining pattern and histologic features were not associated with poor outcome

A

Arabians

Well-differentiated, low mitotic rates (96%)

Uncommon 12%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Elliot et al. 2016. Canine oral mucosal MCT

33 dogs with MCT

Incidence of metastasis?

Adequate local control had improved outcome

A

55%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Scarpa et al. 2016. Cytological grading of canine cutaneous MCT

Number of mitoses, multinucleated cells, bizarre nuclei and presence of karyomegaly

The parameters were significantly different between histologically low-grade and high grade tumors

Accuracy? Sensitivity? Specificity?

How many high grade MCT were not detected?

A

94%, 85%, 97%

4%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Giantin et al. 2014. Global gene expression of canine cutaneous MCT: could molecular profilinf be useful for sybtype classification and prognostication

Significant association was found between mRNA expression and MCT-related mortality for FOXM1, GSN, FEN1, and KPNA2

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Barbosa et al. 2014. Reproducibility of nuclear morphometry parameters from cytologic smears of canine cutaneous MCT-intra and interobserver utility

No significant effects were detected for observer, time, and interaction observer-time

Nuclear morphometric analysis using cytologic smears is reproducible method for grading MCT

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Miller et al. 2016. A retrospetive review of treatment and response of high-risk MCT in dogs

94 dogs with high metastatic risk MCT

Treated with cytotoxic chemo or TKI masitinib, in gross disease or as an adjunct to surgical resection of primary tumor

MST for patients receiving surgery? No surgery

Patients with surgically excised Patnaik gtrade II and high Ki67 in absence of metastatic disease treated with VBL/pred showed significantly _____ survival than those treated with masitinib (MST?)

A

278 days (9 months) vs. 91 days (3 months)

MST 1946 days (5.3 years), 369 days (1 year)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

van Lelyyeld et al. 2015. Comparison between Ki67 index and mitotic index for predicting outcome in canine MCT

Correlation between ki67 index and mitotix index was moderate, while agreement was poor

A high ki67 was?

Mitotic index (>5)

Ki67 showed significant survival difference within the MI <2 but not if >2

High mitotic index predicted death but many dogs with low index also died

A

Sensitive (85%) but poorly specific (58%)

Poorly sensitive (32%) and highly specific (96%)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Ressel et al. 2015. Equine cutaneous MCT exhibit variable differentiation, proliferation activity and KIT expression

Large proportion of tumors were multinodular or diffuse dermal infiltrates of mast cells with mild anisokaryosis, low proliferative rate and sdominanance of KIT pattern I - well differentiated CMCT

1/3 had infiltrative growth, moderate to marked anisokaryosis and high degree of proliferation - poorly differentiated and KIT II and III pattern

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Zorzan et al. 2015. Mutational hotspot of TET2, IDH1, SRSF2, SF3B1, KRAS, and NRAS from human systemic mastocytosis are not conserved in canine MCT

No mutations were found in TET2

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Cemazar et al. 2017. Efficacy and safety of electrochemotherapy combined with preitumoral IL-12 gene electrotransfer of canine MCT

Response rate?

IL-12 gene electrotransfer resulted in __% of patients with detectable serum ___ and ___

A

72%

78%, IFN-g and IL-12

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Mochizuki et al. 2017. Association of breed and histopathological grade in canine MCT

High grade tumor increase with ___ and __ and __ dogs have increased odds of developing high grade tumor

Breed associated with low/intermediate grade

A

advancing age, male and intact dogs

Pug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Barker et al. 2016. Survey of UK-based veterinary surgeons options on the use of surgery and chemotherapy in the treatment of canine high-grade MCT, splenic HSA, and appendicular OSA

Respondents recommend chemotherapy for HGMCT, SHA, and AOS?

Appropriate chemotherapy protocol was not know by __ for HGMCT, SHA, and AOS?

For those not recommending chemotherapy __ did not believe chemo to be efficacious for these tumors

A

90, 40, 57%

25, 51, 36%

29, 64, 65

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Macfarlane et al. 2016. Use of neutrophil to lymphocyte ratio for predicting histopathological grade of canine mast cell tumors

62 cases with gross MCT (14 high grade, 49 low grade)

Median NLR was different between high- and low grade MCT at different locations

Multivariable model identified increasing NLR and age to be associated with increased risk of high-grade MCT

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Mutz et al. 2017. Cytologic comparison of the percentage of mast cells in LN aspirate samples from clinicaly normal dogs vs. dogs with allergic dermatologic disease and dogs with cutaneous MCT

Group 1 - healthy dogs

Group 2 - ADD

Group 3 - MCT on head and limbs

Percentage of mast cells: 0% for 1, 0.05% for 2, and 0.4% for 3

Group 3 - 16 LNs were normal in size and 6 of these had evidence of metastasis

7 LNs were enlarged and 5 had evidence of metastasis

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Milovancev et al. 2018. Reductions in margin lenght after excision of grade II MCT and grade I and II STS in dogs

All processing steps resulted in ____ among MCT samples except between ____ vs. ____, and for STS except between

A

significant reductions, postfixation vs. subgross; ex-vivo vs. postfixation and subgross vs. HTFM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Moirano et al. 2018. Association of prognostic features and treatment on survival time of dogs with systemic mastocytosis: A retropsective analysis of 40 dogs

Dog with metastatic disease confined to distant LN lived ___ than those with circulating mast cells in blood

Metastatic disease in more than 2 sites had ___ prognosis than disease in single location

Administration of chemo over prednisone alone, with combination of lomustine, VBL and pred ___ survival over TKI, toceranib

A

longer

worse

prolonging

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Marconato et al. 2014. Concordance of c-kit mutational status in matched primary and metastatic cutaneous canine MCT at baseline

21 dogs with metastatic MCT

Concordance of mutational status in 21 primary and matched metastatic MCT was __%?

Primary and secondary tumor can be used for c-kit testing

A

100%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Schlieben et al. 2013. Tandem duplication of kit Exon 11 influences the proteome of canine MCT

15 differentially expressed proteins were identified in mutated MCTs

Involves in cytoskeleton structure and cell motility (ACTR2, ACTB, and CAPPA1), cell signaling (ARHGDIA) and lipid metabolism (ALOX15 and ACSBG4), or are serum proteins

The KIT mutation changes the proteome of affected cells with major affect on the composition of cytoskeletal proteome and cell motility proteins.

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Weishaar et al. 2014. Correlation of nodal mast cells with clinical outcome in dogs with mast cell tumor and a proposed classification system for the evaluation of node metastasis

Different histologic patterns of node-associated mast cells correlate with clinical outcome in dogs

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Berlato et al. Comparison of mitotic index and Ki67 index in the prognostication of canine cutaneous MCT

95 dogs

Multivariable analysis, risk of dying due to MCT was ____ in dogs with increased Ki67 (HR 3.0) index or increased mitotic index (HR 2.7)

Mitotic index and Ki67 index were able to differentiate MCTs with worse prognosis

A

Similar

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Worley et al. Incorporation of sentinel LN mapping in dogs with MCT: 20 consecutive procedures

20 MCT in 19 dogs were excised with SLN mapping

__ dogs had SLNs different from closest node

12 dogs had metastasis in extirpated SLN, 7 occured in MCT with MI<5

No correlation was noted between patient stage and c-kit protooncogene

Anatomic sampling of LNs in dogs does not reflect which LNs are receiving the draining tumor lymph

A

8 dogs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Takanosu et al. Sensitive detection of the c-kit c.1430G>T mutation by mutant-specific polymerase chain reaction in feline mast cell tumors

c.1430G>T in c-kit exon 9 was detected in 15.7% of samples by mutation-specific PCR but only in 7.1% by PCR-restriction fragment lenght polymorphism (RFLP)

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Finotello et al. Redox status evaluation in dogs affected by MCT

23 dogs with MCT and 10 healthy dogs

At baseline, dogs with MCT had ____ d-ROMS (reactive oxygen metabolites-derived compounds) and ___ BAP (biological antioxidant potential)

Difference in a-tocopherol?

A

higher, lower

No significant difference

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Warland et al. The utility of staging in canine MCT

220 dogs with MCT were staged with LN palpation/cytology, CXRs, and AUS

___% had metastasis to local LN, __ had distant metastasis

Development of distant metastasis in absence of LN metastasis?

Pulmonary metastasis?

Utility of further staging was low and CXRs not useful in staging MCT

A

30%, 7%

None

None

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Robat et al. Safety evaluation of combination vinblastine and toceranib in dogs: phase I dose-finding study

DLT for combination?

MTD for vinblastine?

MTD for palladia?

Objective response?

A

Neutropenia

  1. 6 mg/m2 EOW
  2. 25 mg/kg PO EOD

50% reduction in vinblastine does not support combination

71% objective response and enhanced myelosuppression suggest synergistic activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Chon et al. Safety evaluation of combination toceranib and piroxicam in tumor bearing dogs (excluding mast cell tumors): a phase I dose finding study

Combination of toceranib at 3.25 mg/kg EOD and piroxicam 0.3 mg/kg/day was safe

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Meyer et al. 2012. CD25 is expressed by canine cutaneous MCT but not by cutaneous connective tissue mast cells

Grade 1 had strong expression of CD25 while grade 3 had decreased levels

CD25 may play a role in early MCT development and may be stimulatory factor for grade I MCT, while grade 3 MCT seem less dependent on CD25

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Mallett et al. 2012. Immunohistochemical characterization of feline MCT

What % of cutaneous MCT, splenic MCT, GI MCT have histamine immunoreactivity?

Seratonin immunoreacticity?

Positive for kit - cutaneous, splenic, GI?

Heterogeneity of MCT based on location

A

20%, 18%, 53%

3 GI and 1 cutaneous MCT

69%, 35%, 33%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Sabbatini et al. 2013. Prognostic significance of kit receptor tyrosine kinase dysregulation in feline cutaneous MCT

24 cats with primary cutaneous MCT

Risk factors affecting survival?

Increased mitotic activity was associated with?

c-kit mutations were how frequent? Influence on prognosis?

67% had different mutatioon in different nodules

A

mitoses>5 per 10 hpf and cytoplasmic c-kit labeling

kit cytoplasmic expression

56% (exon 8 19%, exon 9 71%, exon 11 10%) - not related to protein expression and no influence on prognosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

Amagai et al. Production of stem cell factor in canine mast cell tumors

SCF contributes to proliferation of mast cells in autocrine/paracrine manner

High SCF expression was observed in how many of 7 MCT?

A

5/7

52
Q

Kry et al. Additional local therapy with primary re-excision or RT improves survival and local control after incomplete or close surgical excision of MCT in Dogs

MST for primary re-excision? RT?

Local recurrence in re-excision group, RT group, comparison group?

Chemotherapy and survival and local control?

A

2930 days (8 years), 2194 days (6 years)

13%, 8%, and 38%

Not associated with improved survival or local control

Recommend re-excision or RT with incomplete excision of MCT

53
Q

Elders et al. 2014. Recombinant canine IgE Fc and IgE Fc-TRAIL fusion protein bind to neoplastic canine mast cells

A
54
Q

Halsey et al. Development of an in vitro model of acquired resistance to toceranib phosphate in canine mast cell tumor

Chronic TOC exposure led to c-kit mRNA and protein overexpression

Minimal p-gp activity and no functional p-gp

A
55
Q

Fenger et al. Overexpression of miR-9 in mast cells is associated with invasive behaivour and spontaneous metastasis

miR-9 is increased in high grade canine MCT compared to low grade tumors and normal canine bone marrow derived mast cells

miR-9 overexpression enhanced invasion but no effect on cell proliferation or apoptosis

Causes upregulation of CMA1 - protease involved in activation of MMP and matrix remodeling

A
56
Q

Piviani et al. Significance of mastocytemia in cats

Incidence of mastocytemia in cats with visceral disease or cutaneous disease?

Most common in visceral MCT

A

67%

57
Q

DeWitt et al. A Novel imaging system distinguishes neoplastic from normal tissue during resection of soft tissue sarcomas and mast cell tumors in dogs

A florescent imaging agent that is activated by proteases in vivo was given to dogs 4-6 or 24-26 hr before tumor resection

Imaging system correctly distinguished cancer from normal tissue in?

Sensitivity and specificity?

Toxicity?

A

92%

92% and 92%

53% facial erythema - responded to IV benadryl

58
Q

Rich et al. p62/Sequestosome-I: Mapping Sites of Protein-Handling stress in canine cutaneous mast cell tumors

Significant association with tier-2 (Kiupel) with p62-nuclear immunoreactivity being associated with ____ grade, p62-cytoplasmic with ___ grade

A

low, high

59
Q

Burton et al. Pulse-administered toceranib phosphate plus lomustine for treatment of unresectable MCT in dogs

Toceranib given on day 1, 3, 5 of 21-day cycle (2.75 mg/kg) and on day 3 at 50 mg/m2

DLT?

ORR?

PFS?

Variable associated with improved PFS?

A

Neutropenia

46%

53 days

response to tx, absence of metastasis, no previous chemotherapy

60
Q

Pratschke et al. Evaluation of modified proportional margins approach for surgical resection of MCT in dogs: 40 cases (2008-2012)

Resected with lateral margins equivalent to the widest measured diameter of tumor and minimum depth of 1 fascial plane deep to the tumor

40 tumors were excised with clear margins and 7 with incomplete margins

Local recurrence was 2%

A
61
Q

Schwab et al. Clinical outcome for MCTs of canine pinnae treated with surgical excision (2004-2008)

Local recurrence in 1 dog with grade 2 MCT and 7/8 dogs with grade 3 MCT

MST for grade 1 and 2?

MST for grade 3?

A

Not reached

10 months

62
Q

Baginski et al. The prognostic value of LN metastasis with grade 2 MCT in dogs: 55 cases (2001-2010)

Difference in survival time between dogs with or without LN mets?

MST?

What was prognostic for survival?

Which dogs had greater survival?

A

Not significant

Not reached at 65.9 mo

Tumor location

Greater for dogs that had removal of their metastatic LN

63
Q

Jackson et al. Evaluation of fixation time using Diff-Quik for staining canine mast cell tumor aspirates

Slides were stained in Diff-Quick at varying fixation times (5 sec, 30 sec, 1 min, 2 min)

No difference in staining quality

A
64
Q

Risselada et al. Surgically planned versus histologically measured lateral tumor margins for resection of cutaneous and SQ MCT in dogs: 46 cases (2010-2013)

Surgically mapped lateral margins differed significantly from histologically reported margins in 4 quadrants

Mean histologic margins were __ to ___ smaller than surgical margins

Did BCS contribute to decrease in lateral margins?

A

35% to 42%

No

65
Q

Shoop et al. Prevalence and risk factors for mast cell tumors in dogs in England

What was the prevelance?

Highest breed prevelance?

Which breed showed greater odds of diagnosis?

Which breeds had reduced odds?

Association with diagnosis and sex?

A

0.27%

Boxer 1.95%, GR 1.39%, Weimerainer 0.85%

Boxer, Pug, Staforshire bull terrier compared with crosbred dogs

GSD, Border Collie, WHWT, Springer spaniel, Cocker spaniel

None

66
Q

Grant et al. Clinical response of masitinib mesylate in the treatment of canine macroscopic MCT

39 dogs

Clinical response rate? CR and PR?

Median time to progression?

AEs?

MST?

A

82%, 38.5% and 43.6%

79 days

64% - Elevated ALT 23% and vomiting 15%

159 days

67
Q

London et al. KTN0158, a Humanized Anti-Kit mAb, demonstrates biologic activity against normal and malignant canine mast cells

Blocked mast cell degranulation in vitro

In dogs, well tolerated and reduced cutaneous mast cell number in dose-dependent manner

Clinical benefit in 12 dogs?

A

5 PR and 7 SD regardless of kit mutation status and decreased kit phosphorylation was observed

68
Q

O. Skor et al. Pretreatment leukocyte ratios and concentrations as predictors of outcome in dogs with cutaneous MCT

Relative eosinophil concentration (REC), NER, and LMR were prognostic in univariate analysis

REC and NER were independent predictors of survival in multiple analyses

A
69
Q

Lowe et al. The treatment of canine MCT with electrochemotherapy with or without surgical excision

ECT can be applied succesfully in smaller MCT as alternative to surgery

Can be combined with surgery either intra-op or post-op for larger lesions without significant toxicity

A
70
Q

Sanchez et al. Antihistiminic and cardiorespiratory effects of diphenhydramine hydrochloride in anesthesized dogs undergoing excision of mast cell tumors

Mean diastolic pressure was ___ in diphenhydramine vs. control group

Mean arterial BP was ___ in diphenhydramine vs. control group during surgical closure

IV administration of diphenhydramine prior to MCT excision had no clear clinical cardirespiratory benefits

A

Lower

Lower

71
Q

Bavcar et al. Combination toceranib and lomustine shows frequent high grade toxicities when used for treatment of non-resectable or recurrent MCT in dogs: A European multicenter study

Results?

Objective RR?

A

Severe AEs occured in all dogs

50%

3 dogs died….

72
Q

Dores et al. Comparison of histologic margin status in low-grade cutaneous and SQ canine MCT examined by radial and tangential sections

Low grade MCT, HFTM>0mm should not be considered completely excised particularly when HFTM <10.9 mm

A
73
Q

Shaw et al. Diagnostic accuracy of pre-treatment biopsy for grading cutaneous MCT in dogs

Determine concordane of tumor grade between various biopsy techniques (wedge, punch, needle core) when compared with excisional biopsy

Overall concordance with Patnaik? Kiupel?

Accuracy with wedge, punch, needle core compared to excisional with Patnaik?

Accuracy with wedge, punch, needle core compared to excisional with Kiupel?

A

96% and 92%

92%, 100% and 100%

90%, 95%, 100%

74
Q

Salvadori et al. Effects of electrochemotherapy with cisplatin and peritumoral IL-12 gene electrotranser on canine MCT: a histopathologic and immunohistochemical study

Induced a cellular response characterized by recruitement of T-lymphocytes and macrophages and fibrotic proliferation with reduction of microvessels

A
75
Q

Pizzoni et al. Features and prognostic impact of distant metastases in 45 dogs with de novo stage IV cutaneous MCT: A prospective study

PFI and ST were independent prognostic factors, including?

Negative prognostic factors in multivaraite analysis?

A

Anatomic site, histological grade, mutational status

Tumor diameter > 3cm, 2 metastatic sites, bone marrow infiltration, and lack of tumor control at primary site

76
Q

Milovancev et al. Shaved margin histopathology and imprint cytology for assessment of excision in canine MCT and STS

Positive margin detection for imprint cytology, radial section histopathology, shaved margin histopathology for MCT but not STS

Intermethod agreement was poor

A

21%, 9% and 3%

77
Q

Moore et al. Spinal MCT in dogs: Imaging features and clinical outcome of 4 cases

4 dogs presented for paraspinal hyperesthesia and subacute progressive or acute myelopathy

CT and MRI lesions were extradural

1 dog was nromal 4 years after lomustine

1 recurred within 2 months following surgery despite vinblastine

2 cases were euthanized

A
78
Q

Smith et al. Recurrence rates and clinical outcome for dogs with grade II MCT with low AgNOR count and Ki67 index treated with surgery alone

What % of dogs developed local or distant recurrence?

Of, these dogs, how many developed local recurrence?

Ancillary therapies may not be necessary for patients with incompletely excised grade II MCT with low proliferation activity

A

27%

7% - 1 had complete and 5 had incomplete margins - the difference was not significant

79
Q

Thompson et al. Receptor TK expression profiles in canine cutaneous and SQ MCT

What was predictive of decreased survival time, DFI, and increased metastatic rate?

Increased rate of local recurrence?

A

phosphorylated kit, VEGFR2, and Kit cellular localization

VEGFR2 and kit cytoplasmic labeling

80
Q

Vargas et al. IHC expression of the pluripotency factor OCT4 in canine MCT

OCT4 is not a prognostic indicator for canine MCT

A
81
Q

Foncesca-Alves et al. Ki67/KIT double IHC staining in cutaneous MCT from Boxer dogs

Double positivity was observed in?

Which animals had longer survival time?

A

29%

Ki67-/Kit+ than Ki67+/Kit+

82
Q

Amagai et al. A point mutation in the extracellular domain promotes tumorigenesis of mast cells via ligand-independent autodimerization

A
83
Q

Morimoto et al. Evaluation of the global DNA methylation in canine MCT samples by immunostaining of 5-methyl cytosine

Global DNA hypomethylation was predominant in?

A

Grade 3, high grade, less differentiated MCT

84
Q

Arendt et al. Genome wide association study of golden retrievers identifies germ line risk factors predisposing to MCT

SNP in GNAI2 gene - truncated protein

Hyaluronidase genes were identified as risk factors

A
85
Q

Bauer et al. IL-4 downregulates expression of the target receptor CD30 in neoplastic canine mast cells

CD30 is target in human mast cell neoplasms

A
86
Q

Pulz et al. Increased expression of tissue inhibitor of MP-1 correlated with improved outcome in canine cutaneous MCT

What was associated with post-surgical survival and disease-related mortality?

Dogs with ___ TIMP-1 positivity were more prone to die?

A

TIMP-1

<22.9%

87
Q

Giantin et al. Transcriptomic analysis identified up-regulation of a solute carrier and UDP glucoronyltransferases in dogs with aggressive cutaneous MCT

375 differentialy expressed genes (DEG)

Associated with drug metabolism and cell cycle pathways

Members of solute carrier protein (SCP) and UDP glucoronyltransferases (UGT) genes were dysregulated

A
88
Q

Barra et al. Apoptotic intrinsic pathway proteins predict survival in canine cutaneous MCT

IHC of BAX, BCL-2, APAF-1 and caspace 9 and 3 were performed

High __ expression was associated with higher mortality rate and shorter survival

BCL2 and APAF offered additional prognostic information

A

BAX

89
Q

Halsey et al. Expression of phosphorylated KIT in canine MCT

Expression of __ was significantly correlated with 2-tier grading scheme and c-kit mutation

MCT from 4 of 7 patients had PR to TOC - pKIT expression was assessed by IHC, ____ expression was noted after TOC

A

pKIT

Reduced pKIT expression

90
Q

Guiliano et al. Expression of fibroblast activating protein and correlation with histological grade, MI, and ki67 expression in canine MCT

FAP is serine protease expressed by activated fibroblasts, particularly tumor related fibroblasts (TAF)

What % of MCT expressed FAP

FAP was correlated with Patnaik and Kiupel, MI, and Ki67 expression

High FAP could be a negative prognostic factor in canine MCT

A

90%

91
Q

Jark et al. Genomic copy number variation associated with clinical outcome in canine cutaneous MCT

Regions of loss in PTEN and FAS and regions of gain in MAPK3, WNT5B, FGF, FOXM1, and RAD51 were detected in MCT with short survival times

A
92
Q

Mochizuki et al. Genomic profiling canine MCT identifies DNA copy number aberrations associated with KIT mutations and high histological grade

KIT mutations were less frequent in Pugs tumors and strongly associated with high histological grade

Tumors with kit mutations showed CNA in p53 and RB pathways

A
93
Q

Romanucci et al. HSP32 and HSP90 Immunoexpression in relation ot Kit pattern, grading, and mitotic count in canine cutaneous MCT

All cases had cytoplasmic staining of Hsp90

Relationship between Hsp90 or Hsp32 with KIT pattern, mitotic count and tumor grade?

Reduced Hsp32 in grade III/high grade suggest?

A

Not observed

Poorly differentiated MCs

94
Q

Krick et al. Investigating associations between proliferation indices, c-kit, and LN stage in canine MCT

What were significantly associated with stage?

Sensitivity and specificity of AgNOR?

Recurrent tumors and high AgNORs are associated with?

A

AgNORs/nucleus and recurrent tumors

93% and 27%

Stage II and grade II MCT - AgNOR cutoff value does not predict LN metastasis

95
Q

Keller et al. The JAK2/STAT5 signaling pathway as potential therapeutic target in canine mastocytoma

Inhibitos of JAK2 and STAT5

Results with inhibitors?

Potential target in canine mastocytoma

A

inhibited proliferation and survival in these cells

96
Q

Tamlin et al. Prevelance of exon 11 internal tandem duplication in c-kit protooncogene in Australian canine MCT

Prevalence?

Prevelance in Patnaick grade 3? Kiupel high grade?

Presence of ITD was not associayed with signalment, tumor anatomical location or tumor size

A

18%

55.6% and 50%

97
Q

Stefanello et al. Comparison of 2- and 3-category histologic grading systems for predicting the presence of metastasis at the time of initial evaluation in dogs with cutaneous MCT: 386 cases (2009-2014)

A
98
Q

Sabattini et al. Histologic grading of canine MCT: Is 2 better than 3?

A
99
Q

Camus et al. 2016. Cytology criteria for mast cell tumor grading in dgos with evaluation of clinical outcome

The cytologic grading scheme that best correlated with histology classified as tumor as high grade?

Sensitivity and specificty?

Dogs with histologic and cytologic high grade MCTs were 39x and 25x more likely to die 2-year follow up period

A

Poor granulated or had 2 of the 4 features - mitotic figures, multinucleated cells, nuclear polymorphism, >50% anisokaryosis

88% and 94%

100
Q

Hergt et al. Use of a 2-tier histologic grading system for canine cutaneous mast cell tumors on cytology specimens

Agreement between histologic and cytologic grading was achived in 133 cases - sensitivity and specificity

5 high grade tumor on histology were classified as low grade on cytology

A

87% and 97%

101
Q

Weisharr et al. 2018. c-kit mutation and localization status as response predictors in MCT in dogs treated with Prednisone and toceranib or vinblastine

Dogs treated with TOC 2.75 mg/kg EOD or VBL 2.5 mg/m2 weekly x 4 then EOW

20% of TOC had kit mutations and 30% receiving VBL

RR to TOC and VBL?

Median PFS for TOC and VBL?

MST for for TOC and VBL?

A

46% and 30%

95.5 days and 78 days

159 (5 mo) and 241.5 days (8 mo)

102
Q

Case et al. 2018. Safety and efficacy of intralesional triamcinolone administration for treatment of MCT in dogs: 23 cases (2005-2011)

RR?

Median time to progression?

A

67%

63 days

103
Q

Griffin et al. 2018. Pilot study utilizing flourine-18 fluorodexoyglucose-positron emission tomography/CT for glycolytic phenotyping of canine MCT

Hypothesized enhanced glucose uptake would correlate with grade

Correlation between grade of MCT and SUVmax - unable to show that this is a better staging tool

A
104
Q

Horta et al. 2018. Assessement of canine MCT mortality risk based on clinical, histologic, IHC, and molecular features

A
105
Q

Joselevitch et al. 2018. Nanog expression and proliferation indices in canine cutaneous MCT

NANOG is a pluropotency factor expressed by normal and cancer stem cells

All samples were positive for NANOG but expression not correlated with Ki67 but no significant difference between grade, disease related mortality, or survival

Not reliable prognostic factor

A
106
Q

Gregorio et al. 2017. High COX2 expression in canine MCT is associated with proliferation, angiogenesis, and decreased OS

COX-2 intensity but not COX-2 extension is associated with decreased OS and higher grade of malignancy

Cox-2 intesnity associated with higher ki67, higher MI, higher microvascularization density

No association was observed for COX-2 intensity and CD3 T-lymphocyte and macrophage infiltration by MAC-387 immunolabelling

A
107
Q

Upchurch et al. 2018. Amount of skin affecting tumor versus gross normal marginal skin of dogs for cutaneous MCT excised with curative intent

Overall shrinkage?

Amount of shrinkage with gross visible tumor (4.45%) was less than within the surrounding normal skin (24%)

Most shrinkage occured when?

A

18%

Right after excision

108
Q

Russell et al. 2017. Characterizing microcopial invasion patterns in canine MCT and STS

Invasion in both circumferential and deep directions was greated in?

In MCT group, ___ invasion was greater than ___ invasion

2 variables associated with incomplete MCT excision?

A

MCT vs. STS

circumferential than deep invsion

intraoperative grossly normal circumferantial margin size and assymetry invasion index

109
Q

Marconato et al. Therapeutic impact of regional lymphadenectomy in canine stage II cutaneous MCT

The risk of developing local, nodal, distant relapse was higher in ___ group

Risk of tumor progression and tumor related death were 5.47 and 3.6x higher in ___ group

Regional lymphadenectomy may have therapeutic value and improve prognosis in dogs with stage II MCT

A

LNS - LN sampling

LNS vs. LND (LN dissection)

110
Q

Berlato et al. 2018. Comparison of minichromosome maintenance protein 7, Ki67 and MI in the prognosis of intermediate Patnaik grade cutaneous MCT in dogs

A
111
Q

Sabarrini et al. 2018. Comparison between May-Grunwald-Giemsa and rapid cytological stains in FNA of canine MCT

How many of primary MCT were hypogranular with aqeous rapid stain (RS)

Accuracy in cytological grading assessment (85%) did not differ between RS and MGG

How many metastatic LNs were hypogranular with RS?

Use of RS is discouraged for search of nodal metastases

A

18%

46%

112
Q

Ferrari et al. 2018. The impact of extirpation of non-palpable/normal sized regional LN on staging of canine cutaneous MCT

33 (35%) were HN0, 14 (15%) were HN1, 26 (28%) were HN2 and 20 (21%) were HN3

The presence of positive (HN>0) RLN was associated with cMCT larger than 3 cm

A
113
Q

Blackwood et al. 2017. Acute RT toxicity in 57 dogs with gross and microscopic MCT

57 dogs - 28 gross disease and 29 microscopic disease

No difference in toxicity between gross and microscopic disease

Variable associated with increased toxicity?

A

Use of prednisolone prior to radiotherapy

114
Q

Scarpa et al. 2012. Use of histologic margin evaluation to predict recurrence of cutaneous malignant tumors in dogs and cats after surgical excision

60 surgically excised tumors - 20 STS, 20 MCT, 20 carcinomas

Surgical margins clean 48%, close in 18%, and infiltrated in 33%

Recurrence rates for animals that had infiltrated tumors or close margins were higher than with clean margins

Margin classification was predictor of RFI (recurrence free interval)

Accuracy of method to predict recurrence was 95% carcinomas, 87% STS, 76% MCT

A
115
Q

Evan et al. 2018. Treatment outcomes and prognostic factors of feline splenic mast cell tumors: A multi-institutional retrospective study of 64 cases

Splenectomy (A n=20), splenectomy and chemotherapy (B, n=20), chemotherapy alone (C, n=15), or supportive care (D, n=9)

Median tumor specific survival (MTSS) for A, B, C, D

Splenectomy prolongs survival in cats with MCT. Role of chemotherapy is unknown.

A

A = 856 (2.3 y)

B = 853 (2.3 y)

C = 244 (8 mo)

D = 365 (1 y)

116
Q

Ho et al. 2018. Retrospective study of more than 9000 feline cutaneous tumors in UK: 2006-2013

Prevelence of masses on the skin?

Prevalence of non-malignant and malignant?

4 most common tumors?

A
  1. 4%
  2. 6% and 52.7%

Basal cell tumors, FSA, SCC, MCT

117
Q

Dobromylskyj et al. Evaluation of minichromosome maintenance protein 7 and c-kit as prognostic markers in feline cutaneous MCT

71 feline cutaneous MCT

What factors were associated with survival times?

A

MI and kit labeling pattern, while MCM-7 (proliferation marker) and KIT reactivity score were not

118
Q

Melville et al. 2015. Feline cutaneous mast cell tumors: a UK based study comparing signalment and histological features with long term outcomes

Second most common skin tumors in cats

How many died from MCT?

Median age?

Sex or neuter predilection?

Breeds predisposed?

Common location in older and younger cats?

What was associated with survival time?

A

17.4%

11 years

None

Pedigree breeds - Siamese, Burmese, Russian Blue, Ragdoll

Trunk in older and head in younger

Mitotic index but not histological type

119
Q

Kraus et al. Outcome and Prognostic Indicators in Cats undergoing splenectomy for splenic mast cell tumors

36 cats with splenic MCT undergoing splenectomy

MST?

What factors were negatively associayed with survival?

What was associated with improved survival time?

A

390 days

Blood products, metastasis to regional LN, evidence of concurrent or historical neoplasia

Response to chemotherapy

120
Q

Sabattini et al. 2016. Feline intestinal MCT: clinicopathologic characterisation and KIT mutation analysis

10 tumors in SI, 2 in ileocaecocolic junction, 5 large intestine

Survival times 5-538 days

6 well differentiated, 6 moderately differentiated, 3 poorly differentiated

Poorly differentiated - deposition of collagen, higher mitotic and ki67 index compared to more differentiated tumors

On survival analysis, tumor degree of differentiation and mitotic index >2 were associated with decreased survival time

Kit pattern - membranous (33%), focal paranuclear (33%), diffuse cytoplasmic (13%)

Cytoplasmic kit was associated with lesser differentiation

A
121
Q

Harper et al. 2017. Toxicity and response in cats with neoplasia treated with toceranib phosphate

MCT or malignant epithelial tumors - 14 cats

Toxicity?

Overall biological response rate?

Response in MCT?

Duration of response?

A

10/14 - mild myelosuppression or GI effects, 2 had severe hepatoxicity, 1 died from CHF - unknown if related to palladia

57%

Partial or complete response

3 months

None of the SCC achieved a response

122
Q

Barrett et al. Outcome following treatment of feline GI MCT (FGIMCT)

31 cats with FGIMCT

Mean age?

Metastatic sites?

Therapies: chemo alone (15), surgery and chemo (7), steroids alone (6), surgery and steroids (3)

Most commonly used chemo drugs?

MST?

Treatments associated with prolonged survival?

Treatment other than prednisolone may not be necessary in some cats.

A

12.9 y

Abdominal LNs (10), abdominal viscera (4), both (2)

Lomustine (15) and chlorambucil (12)

531 days (1.5 y)

Surgery and medial treatments (including prednisolone)

123
Q

Berger et al. 2018. Restrospective evaluation of toceranib phosphate use in cats with mast cell neoplasia

50 cats with cutaneous (n=22), splenic/hepatic (visceral) (n=10), GI (n=17), or other (n=1) mast cell neoplasia

Clinical benefit? - cutaneous, visceral, GI

Majority of cats received glucocorticoids during toceranib treatment

Median duration of CB for cutaneous, visceral, GI?

Dosage: 2.5 mg/kg 3x/week

AEs?

A

80% - 86% cutaneous, 80% visceral, 76% GI

36 weeks, 48 weeks, 23 weeks

60% - grade 1 or 2 GI or hematological events

124
Q

Sakuri et al. 2018. Expression of stem cell factor in feline MCT

23 samples of feline MCT

SCF expression?

Location of SCF-positive tumor cells in cutaneous MCT?

Expression of kit in the SCF positive tumors?

Ki67-positive tumor cells?

A

10 cutaneous MCT and a case of splenic mastocytosis

Located at the margins

8/10 cutaneous - kit-positive cells were located near the SCF-positive cells

Not found near the SCF-positive cells

SCF-autocrine/paracrine mechanism are involved in the expansion of cutaneous MCT, but not in tumor proliferation

125
Q

Sabattini et al. 2018. Grading Cutaneous MCT in Cats

Group 1 - cats alive with no MCT-related disease 1000 days from surgery

Group 2 - cats developing histologically confirmed metastatic or cutaneous disseminated disease

High grade - >5 mitotic figures abd atleast 2 criteria - tumor diameter >1.5 cm, irregular nuclear shape, and nucleolar prominence/chromatin clusters

24% of high grade MCT had reduced survival time (349 days) compared to low grade tumor - MST not reached

Further studies are warranted

A
126
Q

Elbahi et al. Histiocytic-like atypical mast cell tumors in Horses

1-2cm in diameter and localized to the eyes (one eyelid, 2 conjunctiva)

A