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Onco Board Review 2 > Melanoma > Flashcards

Melanoma Flashcards

1
Q

What are the four IHC markers in the melanoma cocktail? What else can be used?

A

PNL2, melan-A, TRP-1, TRP-2

Also S-100

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2
Q

What is the sensitivity and specificity of the melanoma cocktail?

A

Sn >90%, Sp 100%

Smedley Vet Path 2011

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3
Q

T/F: BRAF mutations are common in canine melanoma.

A

False

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4
Q

Name two pathways that are constitutively activated in melanoma and can be effectively targeted in vitro?

A

MAPK and PI3K/AKT
(Fowles 2013)
- rapamycin inhibits PI3K/AKT

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5
Q

In canine oral melanoma, which proliferation index (IHC) predicts behavior and what is the significant level?

A

Ki67 value of >19.5
Sn 87.1%/Sp 85.4% at predicting death/euthanasia by 1yr post-dx
(Bergin Vet Path 2011)

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6
Q

For oral and cutaneous melanoma in dogs, what are the MI cut-offs?

A

Oral >/= 4/10 hpf

Cutaneous >/= 3/10 hpf

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7
Q

What is the approximate MST for stage 1 oral melanoma tx with surgery?

A

Withrow - 17-18mo
Boston - 20mo
Tuohy - 24mo

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8
Q

What is the approximate MST for stage 2 or 3 melanoma tx with surgery alone?

A

Withrow - stage 2 = 5-6mo, stage 3 = 3mo

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9
Q

What is the approx. recurrence rate for melanoma tx with matxillectomy and mandibulectomy?

A

Maxillectomy - 48%

Mandibulectomy - 22%

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10
Q

What is the likelihood of dying from disease with incomplete margins?

A

3.6x more likely to die

caudal tumor 4.3x more likely

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11
Q

What is the RR of melanoma to RT? PFS?

A

82-94%
PFS 5-8 mo
(for feline - 3/5 cats (60% RR) in Farrelly paper)

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12
Q

What is MST for oral melanoma tx with RT alone?

A

7-10mo depending on study

2015 Kawabe JAVMA:

  • stage 1: 2yrs
  • stage 2: 9mo
  • stage 3: 5mo
  • stage 4: 2.7mo
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13
Q

What is the likelihood of tumor progression/recurrence after RT for oral melanoma? (adjuvant vs. RT alone)

A

microscopic - 26%

macroscopic - 45%

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14
Q

What is the RR to platinum chemo for canine melanoma?

A

18-28%

Boria/cisplatin = 18%, Rassnick/carbo = 28%

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15
Q

What proportion of dogs develop humoral immune response to xenogeneic tyrosinase vaccination? Horses?

A

Dogs - 1/3 (3 out of 9)

Horses - 100% (5/5 in Lembcke Equine Vet Sci 2012)

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16
Q

How does PDGFR impact prognosis in canine melanoma? (Lussich VCO 2016)

A

PDGFRa and B receptor co-expression and Ki67 values >19.5 were both associated with worse prognosis

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17
Q

What adjuvant therapy may improve time to progression in dogs with oral melanoma after RT? (Cancedda VCO 2014)

A

temozolomide

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18
Q

What % of dogs have AE to melanoma vaccine? (Sarbu 2015)

A

11% - grade 1-2 pain, muscle fasciculation, nausea/inappetence, pigmentation at injection site

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19
Q

Two prognostic factors for feline non-ocular melanoma? (Luna 2000, Chamel 2016)

A

Amelanotic vs. pigmented

surgical vs. nonsurgical tx

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20
Q

Describe stage 3 oral melanoma.

A

Tumor >4cm and/or RLN involvement, no distant metastasis (that would be stage 4).

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21
Q

Stage 1 melanoma treated appropriately has reported MST of?

A

12-19 months

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22
Q

What % of dogs with OMM have LN mets with normal palpation?

A

40%

70% when nodes are big

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23
Q

Why are hypofractionated RT protocols more effective in OMM?

A

Low alpha:beta ratio

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24
Q

What is the %CR of OMM to RT?

A

51-69%

PR 25-31%

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25
Q

What is the significance of c-kit expression in melanoma? (Newman Vet Path 2012)

A

Loss of c-kit common in neoplastic tumors; potential for prognostic indicators
c-kit was strong and diffuse in all dermal melanomas

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26
Q

What was the incidence of BM and GI toxicity in dogs with various tumors treated with dRT and concurrent carbo?

A

21% grade 3-4 neutropenia; 20% grade 3-4 thrombocytopenia

10% grade 3-5 GI tox

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27
Q

T/F: Carbo reduces the proportion of dogs with OMM that die of metastasis?

A

False

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28
Q

T/F: Dogs with higher plasma VEGF treated with RT have shorter time to tx failure and shorter MST.

A

True (Taylor VCO 2007)

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29
Q

What 4 criteria must be met to diagnose a radiation-induced tumor?

A
  1. develops in previously irradiated site
  2. adequate time has passed (> 1 year)
  3. Pre-irradiation revealed normal bone
  4. Histologic dx of a second, different malignant tumor confirmed
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30
Q

What are the most common RT-induced tumors?

A

sarcomas

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31
Q

What two negative prognostic factors were identified in dogs with digital melanoma tx with the vaccine?

A
  1. advanced stage dz

2. increased time from digit amp to starting vaccine

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32
Q

Is the Wnt B-catenin pathway activated in oral melanoma?

A

No

33
Q

Is the Wnt B-catenin pathway activated in cutaneous melanoma?

A

Yes

34
Q

What is the biologic activity of Palladia against canine melanoma? (London 2003)

A

54%

35
Q

What was the 1 year survival rate for dogs with digital melanoma treated with a murine tyrosinase DNA vaccine?

A

63%

MST = 476d

36
Q

What were the effects of an anti-PD-L1 antibody in vitro? What were effects in 7 dogs with OMM and 2 with undifferentiated sarcoma? (Maekawa 2017)

A

in vitro - increased cytokine production and proliferation of dog mononuclear cells
OMM - objective response in 1 dog
Sarc - objective response in 1 dog

37
Q

What is prognostic in non-ocular melanoma in cats? (Chamel 2016)

A

amelanotic associated with worse prognosis

38
Q

What is IQGAP1? Is it expressed in human and/or canine melanoma? (Lee PLoS One 2017)

A

It is a signaling scaffold that regulates oncogenic ERK1/2 MAPK signaling in human Ras and Raf driven cancers
Yes, expressed in both human and canine melanoma.

39
Q

What is bosutinib? How did it affect melanoma cells?

A

SRC inhibitor

Caspase-independent apoptosis

40
Q

In a study by Grimes et al in 2017, what was the conclusion regarding agreement between cyto and histo for LN metastasis and association with survival?

A

Poor agreement, no association with survival.

41
Q

What was PFS and MST in dogs with malignant anal sac melanoma, regardless of tx? (Vinayak 2017)

A 
PFS 92.5d (3mo)
MST 107d (3.6mo)
42
Q

What is Oncept vaccine licensed for?

A

Stage II-III OMM with adequate local control

43
Q

How does Pgp expression differ between oral and cutaneous melanoma? (Finotello 2016)

A

100% expressed in OMM, 66.6% expressed in cutaneous

Could be a reason for chemo resistance

44
Q

What does binding of PD-L1 to PD-1 cause?

A

When PD-L1 binds PD-1 on T cells –> negatively regulates activation signals from T cell receptor –> results in inhibition of effector function of cytotoxic T cells

45
Q

What cancers express PD-L1? (Maekawa PLoS One 2016)

A

melanoma, OSA, cHSA, MCT, mammary ACA, prostate ACA

46
Q

In a study by Skinner et al (2016), what % of dogs with malignancies of the head had LN mets?

A

45%

47
Q

In a study by Skinner et al (2016), what % of the dogs with metastasis had mets to the contralateral node?

A

62% (92% had ipsilateral mets)

48
Q

In a study by Skinner et al (2016), what % of the dogs OMM had mets to all four lymph centers?

A

4 of the 13 (30%)

Based on this study, recommend extirpation of all four LN with head/neck tumors, especially OMM.

49
Q

How did 2 year survival of OMM with CSPG4-antigen electrovaccination compare to surgery alone?

A

30.4% vs. 5.3%

50
Q

What % of dogs with stage II-III melanoma die within 1 year of surgery?

A

70-75%

51
Q

What pattern of PDGFR expression is associated with worse prognosis?

A

PDGFR-alpha and beta co-expression.

52
Q

What % of cats had AE to melanoma vaccine?

A

29%; all were mild

53
Q

Is IL-12 pro-inflammatory or anti-inflammatory? How does it work?

A

Pro-inflammatory cytokine. Mediates Th1 response and cytotoxic T-cell activation.

54
Q

What is NHS-IL12? (Paoloni PLoS One 2015)

A

antibody that targets necrotic tumor regions linked to IL-12

55
Q

What two markers in the serum increased after NH-IL12 administration? Did any of the dogs respond? (Paoloni PLoS One 2015)

A 
IL-10 and CD8+ increased in serum.
2 dogs (out of 18) responded (was not primary endpoint for the study)
56
Q

What are the prognostic factors for survival post curative-intent surgery for OMM? (Tuohy 2014)

A

administration of adjuvant therapy; presence of mets at dx; higher stage (III or IV); tumor size >3cm; intact female dogs
(note that admin of adjuvant therapy associated with 130% risk of dz progression - prob gave adjuvant therapy to worse cases)

57
Q

What was the median PFI and MST for curative-intent surgery for canine OMM? (Tuohy 2014)

A 
PFI 508d (1.4y)
MST 723d (2y)
58
Q

What is the role of miR-203 in human and canine melanoma? (Noguchi 2016)

A

tumor-suppressive miRNA

59
Q

What are cancer stem cell markers (used to identify CSCs in OMM in Guth 2014)?

A

CD133, CD34, CD44, CD24, Oct3/4

This study found that CSCs were rare in cancer cell lines in comparison to tumor samples

60
Q

What were poor prognostic indicators in Boston et al 2014 (evaluating adjuvant therapy in 151 OMM cases)?

A

tumor size, patient age, intralesional excision (vs. marginal, wide, or radical)

61
Q

Did Boston et al 2014 identify survival benefit for adjuvant therapy with canine OMM?

A

No – no post op-tx MST was 335d, with post-op tx MST was 352d
(small sample sizes)

62
Q

Does maropitant have anti-tumor effect in melanoma xenograft models? (Borrego 2016, Vail)

A

No; did have effect in cell lines but likely off-target

Study failed to ID cell line or xenograft that has NK-1R mRNA or protein (neurokinin-1 receptor)

63
Q

Four genes with increased expression in metastasizing uveal melanoma (Malho 2013)

A

HTR2B, FXR1, LTA4H, CDH1

64
Q

What proteasome inhibitor inhibits growth of canine melanoma cells in vitro and in vivo? (Ito K 2013)

A

bortezomib

growth inhibition may be secondary to suppression of NFkB pathway

65
Q

Levels of ___ and ___ were decreased in K9 OMM xenograft models when treated with CTX + piroxicam. (Choisunirachon VCO 2015)

A

MVD and VEGF

66
Q

Is the Wnt/B-catenin pathway activated in canine OMM? (Chon 2013)

A

No (rare)

67
Q

Does expression of tyrosinase correlate with pigmentation in dogs? Horses? (Phillips 2012)

A

No for both

68
Q

Is c-kit expression a positive or negative prognostic indicator in canine mucosal melanoma? (Newman 2012)

A

positive (loss of expression correlated with decreased survival)

69
Q

What is p21/Waf-1?

A

Universal CDK inhibitor - loss of function permits cell growth. May have a role in melanoma cells (TLM-1).

70
Q

What tumor suppressors May play a role in malignant melanoma?

A

p53, p21/waf-1, p16/ink-4a

71
Q

What does the Oncept vaccine encode for?

A

The Oncept vaccine uses xenogeneic DNA plasmids that contain the gene encoding human tyrosinase (huTyr)

72
Q

What is the MST after enucleation for feline uveal melanoma that has invaded into the ciliary body and sclera?

A

1.5 yrs

73
Q

T/F: Enucleation improves MST in cats with malignant uveal melanoma?

A

False

74
Q

What is the metastatic rate of feline malignant melanoma of the anterior uveal?

A

55-66%

75
Q

What % of canine intraocular melanomas are benign?

A

78%

76
Q

What is the most common malignant tumor of the canine conjunctiva?

A

melanoma

77
Q

T/F: Most feline eyelid tumors are malignant?

A

True

78
Q

What were results with L-MTP-PE and melanoma? (Withrow)

A

stage I oral melanoma that received L-MTP-PE had increased survival over placebo dogs

79
Q

What is the 1 year survival rate for dogs with digital melanoma?

A

42-57%

Onco Board Review 2 (20 decks)

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