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Onco boards 2024 > Principles of cancer part II AB > Flashcards

Principles of cancer part II AB Flashcards

1
Q

CD 45

A

All Leukocytes
- not expressed on erythroid leukemias
- CD45- INDOLENT LSA

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2
Q

CD1

A

MHC class 1 proteins A-E

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3
Q

CD3

A

T cell receptor complex
- T cell LSA
- epsilon, delta, gamme component
- epsilon is where Ab sticks
- positive in chickens with Maricks

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4
Q

CD4

A

T helper cells binds to MHC II
- T cell LSA

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5
Q

CD8

A

cytotoxic T cells bind MHC class I
- T cell LSA

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6
Q

CD11

A

one chain of a/b heterodimeric B2 integral that helps leukocytes binds to cells
- 4 types A-d

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7
Q

CD11d

A
  • T cell subset (splenic), Macs, histiocytes
    HS, LGL
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8
Q

CD14

A

Monocytes
- LPS macrophages
- monocytes leukemia

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9
Q

CD18

A

common beta chain on all leukocytes
- can distinguish HS from STS
- cannot distinguish HS from LSA

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10
Q

CD20

A

mature B cell
- NOT on plasma cells
- rituximab tagets

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11
Q

CD21

A

mature B cell
- NOT on plasma cells

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12
Q

CD25

A

alpha chain of IL-2 receptor on activated T cells and Tregs
- used for Tregs most commonly

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13
Q

CD31

A

platelet Endothelial cells adhesion molecule 1 (pecam1)
- HSA, pCam1

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14
Q

CD79a

A

B cell receptor
- ON PLASMA CELLS
- pro B cell through plasma cells

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15
Q

CD204

A

class A scavenger for Macs
- on 50% HS

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16
Q

CD34

A

hematopeotic stem cells

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17
Q

CD11b

A

granulocytes, monocytes
- myelomonocytic myeloid leukemias

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18
Q

CD11d+ and CD8+ cell

A

LGL morphology

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19
Q

myeloperoxidase

A

myeloid lineage leukemias

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20
Q

CD11c

A

dendritic cells

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21
Q

CD1a

A

dendritic cells, cortical thymocytes
- immature t cells

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22
Q

Mediastinal mass CD5+ CD4+ CD8+

A

thymoma = dog
LSA = cat

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23
Q

CD5

A

T cells and some B cells
- TZL

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24
Q

MHC II

A

mature B cell
- B cell LSA

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25
Q

CD 117

A

KIT immunolabeling
- MCT, T cell LSA, various

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26
Q

Surface IgM

A

immature B cell
- B cell LSA

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27
Q

Surface IgG

A

Mature B cell
- B cell LSA

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28
Q

Node CD45-, CD5+, CD21+

A

TZL

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29
Q

Increased JAK/STAT signaling associated with which tumors?

A

MCT, HSA, thyroid carcinoma, AGASCA
- pSTAT3 correlated with metastasis for MCT
- increased JAK1 survival for MCT and HSA

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30
Q

PD-1/PD-L1 expression found on what cells?

A
  • activated T cell and peripheral blood mononuclear cells in canine
  • production of IFN-y secreting T cells increased significantly with anti-PD-1 Ab alone in in vitro
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31
Q

Preconditioning of canine adipose tissue derived mesenchymal stem cells with deferoxamine can reprogram to which TAM phenotype?

A

M2 to aid in anit-inflammatory effects

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32
Q

PDL1 membranous labeling on which tumor types?

A

Melanoma 100%
Renal cell carcinoma 24%
SCC 18%
Pulmonary carcinoma 10%
Mammary carcinoma 3%

  • NONE on GI carcinoma
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33
Q

Which cancer have been found to have high infiltrates of tregs?

A

OMM, oSCC, pulmonary adenocarcinoma and mammary carcinoma

  • OST sig shorter for high tregs vs low tregs in OMM, oSCC, and PA
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34
Q

IBA1

A

pan macrophage maker
- ionized calcium binding adapter molecue

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35
Q

DOG1

A

interstitial cells of Cajal
- GIST

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36
Q

Actin

A

smooth/skeletal m

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37
Q

E-cadherin

A

adhering junction of epithelial cells (carcinomas)
- specific to Langerhans cells over other types of macs

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38
Q

Calponin

A

polypeptide that modulates atpase during smooth m contraction

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39
Q

CD10

A

renal promiximal tubular epithelium and lymphoid progenitor cells Ag
- renal carcinomas, ALL

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40
Q

CD90

A

aka thy-1
- thyme t cell

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41
Q

Chromogranin A

A

neuroendocrine tumors

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42
Q

Claudin 7, CK7

A

hepatocellular vs biliary carcinoma in bile duct epithelial cells

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43
Q

CNPase

A

oligodendrogliomas

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44
Q

cytokeratin

A

skin

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45
Q

desmin

A

musle - leiomyomas/sarcomas, rhabdos

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46
Q

factor VIII related Ag

A

vWF, endothelial differentiation
- HSA, lymphangiosaercomas
- diff HSA from telangiectatic OSA

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47
Q

Glucagon

A

pancreatic islet alpha cells - glucagonomas

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48
Q

Glypican 3

A

HCC
- not in chloangio, cirrhotic, or normal liver
- more sn than heppar1

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49
Q

hepatocyte parafin 1

A

specific for HCC

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50
Q

inhibin alpha

A

gonadal sex cord stromal tumors, adenrocortical tumors

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51
Q

Insulin

A

pancreatic beta cells - insulinoma

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52
Q

Melan A

A

specific for melnoma
also on Sertoli and leydig tumors

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53
Q

mesothelin

A

mesothelial and epithelial cells

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54
Q

mullerian inhibiting substance

A

Sertoli cells NOT leydig

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55
Q

MUM1

A

plasma cells

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56
Q

MyoD1

A

rhabdos

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57
Q

myoglobin

A

skeletal muscles

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58
Q

napsinA

A

pulmonary adenocarcinoma not SCC or mesothelioma

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59
Q

NXK 3..1

A

may be able to distinguish prostatic from UC

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60
Q

olig-2

A

oligodendrocyte

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61
Q

p63

A

myoepithelial cells of ductular-lobular epithelial
- distinguishes invasive vs non invasive carcinomas

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62
Q

PAX 5

A

pre B cell marker
- B cell LSA
- positive for avian leukosis

63
Q

pax 8

A

renal and thyroid epithelium

64
Q

periaxin

A

Schwann cells, transmissible facial tumors in devils

65
Q

PNL2

A

monoclonal AB for melanoma
- more specific than melan A in dogs
- 100% + in horse melanoma where melan A is not

66
Q

synaptophysin

A

neural tissue, neuroendocrine cells

67
Q

BLA 35

A

Hodgkins LSA in cats

68
Q

Ki67

A
  • all phases of M phase, absent in non cell cycling
  • melanoma and MCT primarily
69
Q

AgNOR

A
  • expressed during high transcription activity
  • MCT
70
Q

Intratumoral micro vessel desnsity

A

angiogenesis, MCT

71
Q

cyclins CDK

A

cell check points

72
Q

Prox-1

A

lymphatic epithelium

73
Q

RACK1

74
Q

S-100

A

neuronal tissue
- distinguish schwannomas from neurofibromas and fibro

75
Q

somatostatin

A

pancreatic endocrine cells

76
Q

surfactant protein A SP-A

A

alveolar type II cells and Clara cells
- pulm carcinomas with TTF1 or napsin

77
Q

Thyroglobulin

A

follicular carcinomas with TTF1

78
Q

Uroplakin III

A

transitional epithelium
- UC
- fibroblast activation marker of CAFS

79
Q

Villin

A

colorectal and pulmonary caricnoms

80
Q

Vimetin

A

intermediate filament
- distinguish between epithelial and mesenchymal tumors
- can use with cyokeratin for mesothelioma (cytokeratin +, vimentin
+)

81
Q

a-SMA

A

fibroblast activation marker of CAFS

82
Q

What do cancer associated fibroblasts (CAFs) arise from? How they activated?

A
  • bone marrow-derived cells or transdifferentiation from epithelial/endothelial cells
  • TGFb
83
Q

How do CAFs contribute to cancer?

A
  • GF signaling: HGF, FGF
  • survival: IGF
  • ECM remodeling: intigrens, MMP and ADAM proteinase expression
  • chemokines: SDF-1, CXCL12, IL2, CXCL8
  • angiogenesis: VEGF
  • mice deficient in CAFs have reduced metastasis/tumor growth –> CAFs = poor prognosis
84
Q

Markers of CAFs

A

a-SMA, FSP-1. FAP, neuron-glial antigen2, PDGFGb

85
Q

What is meant by intraturmoral vs intertumoral heterogeneity?

A

cancer cells within an individual are as diverse as the same cancer amongst various individuals

86
Q

What are the coexisting theories of tumor heterogeneity?

A
  • EMT: cells transdifferentiate to more motile mesenchymal phenotype via TGFb, Wnt, PDGF
  • CSCs: a minority of cancer cells have the potential to self renew, proliferate, and differentiate (variations in types, long vs short term).
  • role in chemo/RT resistance, responsible for recurrence when control appears complete
  • Phenotypic plasticity: cell populations are in dynamic equilibrium controlled by epigenetics, cells can switch btw diff. phenotypes in response to microenvironmental stimuli.
  • Cells are the periphery are different than cells in the core
87
Q

CSC markers?

A
  • High ALDH and ABCB1
  • high CD44, low CD24
  • CD133 = brain/colon
  • CD34 = myeloid
  • ESA = colon
88
Q

How does tumor heterogeneity impact clinical practice?

A

precision medicine:
- tumor genome sequencing for individual draggable targets
- liquid biopsy for mutation (V600E used in humans ctDNA) for diagnosis/monitoring
- CTCs act as a surrogate for presence/absence of some tumors

89
Q

What is a barrier to precision medicine (sequencing individual tumor)?

A
  • intratumoral heterogeneity - resistant sub clones outcompete tumor clones
  • may be able to overcome with combinations therapy e.g. MEK and BRAF targeting
90
Q

What is differentiation therapy? Example?

A

strategy to overcome tumor heterogeneity by using agents that cause EMT/CSC differentiation to make them more susceptible to therapy

  • check point inhibitors
91
Q

What is the concept of adaptive therapy?

A

use of patient specific tumor dynamics to make decisions about when to treat and not to treat with the same effective tx in the individual

goal: suppress proliferation of treatment resistant cell while extending the duration of therapy while lowering drug exposure

92
Q

How do CSC contribute to tumor resistance?

A
  • remain quiescent making them less responsive to therapy –> activity later in disease –> prog/mets
  • high levels of ABC transporters
  • multiple DNA repair mechanisms
  • interact w/ TME (CAFs, Tregs) to make a more favorable environment for survival
  • CSCs can give rise to non-CSC progeny that may be more sensitive to therapy, but the presence of CSCs ensures the continued survival and regeneration
  • interaction with signaling pathways: HH, wnt, NOTCH, tgfb
93
Q

How can you reverse CTX resistance in stem cells?

A

PARP inhibitor

94
Q

How do stem cells contribute to RT AE?

A

Help repair acutely damaged tissues = high a/b

95
Q

Increased SHH signaling causes?

A

Proliferation, invasion, mets

  • embryogenesis, angiogenesis, and activation of CSC
96
Q

Result of CSC upregulation of B-catenin?

A

longer telomeres

97
Q

CSCs and radiation

A
  • CSCs can regenerate tumors after tx
  • their radio sensitivity is crucial to control - knowing the radiation sensitivity and # of CSC would allow prediction of survival following in RT tx
  • dose of RT to control a tumor depends on # of CSC
  • difficult to predict due to various phenotypes, TME, etc
98
Q

CD133 and Oct-4 expressing cells are radio resistant vs adherent?

A

radio resistant

  • these are CSCs sphere forming cells
  • CSC resistance may depend on reaction of DNA dsbreak after RT
99
Q

Lymphoma cells resistant to CHOP have upregualation of?

A

CD133, ALDH, and readily formed spheres = CSC

100
Q

Carcinogenesis: initiation, promotion, & progression

A

initiation: process by which carcinogenic event interacts with DNA to prove damage that cannot be repaired –> error prone DNA replication –> fixed mutation in genome

promotion: clinical expansion of an initiated cell as a result of altered gene expression

progression: lesions acquire the ability for further growth, invade adjacent tissues, and met (may occur slowly and/or never manifest in life)

101
Q

Which stage of carcinogenesis is reversible?

102
Q

Are most carcinogens direct acting or do they require activation?

A

most require activation to electrophilic state to induce DNA damage

103
Q

Define/explain how the promotion step of carcinogenesis manifests clinically?

A

Promotion = expand cell proliferation results in survival and proliferation of cells and clinically many pre-neoplastic lesions (e.g. polyps, nodules, papillomas)

104
Q

How do chemicals contribute to the carcinogenic process?

A

DNA damage producing somatic mutations

105
Q

Shared characteristics of genotoxic chemicals

A

directly elecrtrophilic (e- seeking), capable of conversion to electrophiles typically via P450 to electrophilic metabolic –> interact with neucleophilic (electron rich) groups on intracellular molecules (DNA, proteins) to form covalent adducts or oxidative damage

106
Q

Chemical factors associated with carcinogenesis

A
  • tobacco smoke
  • Pest, herb, insecticides (specifically 2,4,-dichlorophenoxyacetic acid [2,4-D])
  • cyclophosphamide - UC in people and dogs via acrolein
  • pollutants
107
Q

Physical factors associated with carcinogenesis

A
  • UV exposure (SCC)
  • trauma/chronic inflammation
  • magnetic fields
  • RT
  • SX implants
  • asbestos
108
Q

Which tumors have an increased risk of development following castration?

A
  • cardiac tumors
  • OSA (purebred, Rottweilers <1 yr of age at castration)
  • Prostatic epithelial tumors (including UC)
  • UC
  • LSA (Goldens <1 yr at castration)
109
Q

Which tumors have a decreased risk after castration?

A

testicular

110
Q

Which tumors have an increased risk of development after spay?

A
  • cardiac (esp HSA)
  • OSA (purebred, rotties <1yr at spay)
  • splenic HSA (esp viszlas, godens <1 yr spay)
  • MCT (esp viszlas, goldens)
  • LSA
111
Q

Which tumors have a decreased risk after spay?

A
  • Ovarian
  • Uterin
  • mammary (spay b4 3rd estrus; feline and canine)
112
Q

Mareck virus type/class, animal, tumor?

A
  • DNA/herpes
  • Chickens
  • lymphoid with bursa
113
Q

Papilloma virus type/class, animal, tumor?

A

-non enveloped DNA
- dogs, cats, cattle, horses
- papillomas, Bowen’s dz in cats, sarcoids in horses

114
Q

Woodchuck virus type/class, animal, tumor?

A
  • dsDNA/orthohepadnavir
  • Woodchuck
  • HCC
115
Q

Feline sarcoma virus, virus type/class, animal, tumor?

A
  • RNA/acute trans
  • Cat
  • fibrosarcoma
116
Q

Reticuloendotheliosis virus type/class, animal, tumor?

A
  • RNA/ acute = chicken, lymphoid without bursa
  • RNA/chronic = Fowl, B or T cell LSA
117
Q

Avian leukosis virus type/class, animal, tumor?

A
  • RNA/chronic
  • chicken
  • B cell LSA
118
Q

Rous sarcoma virus type/class, animal, tumor?

A
  • RNA/chrnoic
  • chicken
  • sarcoma
119
Q

lymphoproliferative dz virus type/class, animal, tumor?

A

-RNA/chronic
- turkey
- marbled spleen

120
Q

FIV virus type/class, animal, tumor?

A
  • RNA/ chronic/ lenti
  • cats
  • lymphoid, SCC, myeloproliferative dz
121
Q

FeLV virus type/class, animal, tumor?

A
  • RNA/chrnoic/oncovirinae
  • cat
  • lymphoid
122
Q

Bovine leukemia virus virus type/class, animal, tumor?

A
  • RNA/chronic
  • cow
  • LSA
123
Q

Which are DNA viruses?

A
  • hepatitis B = HCC
  • adenovirus
  • papilloma virus
  • polyomavirus
  • Epstein Barr - Burkitts LSA
  • HHV8 = capos sarcoma, endothelial tumors, NHL
124
Q

Which are retroviruses?

A

Human T lymphocytic virus type 1, hepatitis C, HIV

125
Q

RNA viruses associated with cancer?

A

Hep C, human T lymphocytic virus type1, FeLV, Feline sarcoma, FIV

126
Q

Which is true about FeLV?

A

type c: <1% of cats, early erythroid precursors affected die within 1-2 mo

127
Q

FeLV vaccines protect against ?

A

1 variant of subgroup A

  • FeLV A occurs in all infected cats and causes immunosuppression, associated with natural transmission
  • FeLV B occurs in 50% of all infected cats and causes neoplasia more than A alone
  • Subgroups A and B – recombine w proto-oncogenes MYC or TCR
  • FeLV C causes severe anemia in <1% of ctas
128
Q

What is the function of the E6 and E7 HPV proteins?

A

E6- targets p53 for degradation via ubiquitin pathways
E7- binds/inhibits Rb

129
Q

Risk of developing LSA in FeLV + cats?

A

6.2x higher

130
Q

Tumor types associated with obesity?

A
  • UC in Scottish Terries
  • OSA
  • mammary
131
Q

Tumor types associated with diet?

A
  • mammary - red meat intake, fat, and table food
  • vegetable intake reduces risk of UC
132
Q

Tumor types associated with environmental pollutants?

A
  • anthracosis - pulmonary cancer
  • urban area - LSA
  • kerosene/coal exposure - nasal carcinoma
133
Q

Tumor types associated with pesticide exposure?

A
  • LSA
  • UC - flea tick products too
134
Q

Tumor types associated with tobacco smoke?

A
  • nasal carcinoma in dolichocephalic breeds
  • LSA
  • SCC
135
Q

Carcinoma: molecular markers & localization/expression?

A
  • cytokeratin+, vimentin -
  • both cytoplasmic
  • coexpression can occur in mesotheliomas and may reflect EMT in carcinomas
136
Q

GIST: molecular markers & localization/expression?

A
  • *KIT (CD117)+/- = PM and cyto
  • SMA+/- = cyto
  • Desmin- = cyto
  • s100- = N & cyto
  • *dog1+ = PM and cyto
137
Q

HSA/lymphangiosarcoma: molecular markers & localization/expression?

A
  • Factor VIII-RAg/vWF+ = cyto
  • CD31/PECAM1+ = PM & cyto
138
Q

HS: molecular markers & localization/expression?

A
  • CD18+ = PM
  • CD3- = PM
  • CD79a- = PM
  • Pax5- = N
  • IBA1+ = cyto
  • lysozyme +/- = cyto
139
Q

Leiomyosarcoma: molecular markers & localization/expression?

A
  • KIT/CD117- = PM & cyto
  • SMA+ = cyto
  • Desmin +/- = cyto
  • s100- = N and cyto
  • Dog1- = PM & cyto

desmin confirms myosin origin but does not differentiate between smooth, striated, or cardiac m

140
Q

B cell LSA: molecular markers & localization/expression?

A
  • CD18 +/- = PM
  • CD3- = PM
  • CD79a+ =PM
  • PAx5+ = N
  • CD20+ = PM
141
Q

T cell LSA: molecular markers & localization/expression?

A
  • CD18+/- =PM
  • CD3+ = PM
  • CD79a- = PM
  • PAX5- = N
142
Q

Null cell LSA: molecular markers & localization/expression?

A
  • CD18-
  • CD3-
  • CD79a-
  • PAX5-

all PM except PAX5 N

143
Q

MCT: molecular markers & localization/expression?

A
  • Tryptase+ = cyto
  • KIT/CD117+ = PM and/or cyto (type I-III expression pattern)
144
Q

Melanocytic: molecular markers & localization/expression?

A
  • Melan-A +/- = cyto
  • PNL2 +/- = cyto
  • Tyrosinase +/- = cyto
  • TRP1 or 2 +/- = cyto
  • Vimentin + = cyto
  • s100+ = N & cyto
145
Q

Mesothelioma: molecular markers & localization/expression?

A
  • cytokeratin +/-
  • vimentin +/-
  • both cyto
  • coexpression for most mesotheliomas
146
Q

Neural astrocytic tumor

A
  • GFAP+ = cyto
  • s100+/- = N & cyto
  • Olig2+/- = N
147
Q

Neuroendocrine: molecular markers & localization/expression?

A
  • Chromogranin A +/- = cyto
  • Synaptophysin +/- = cyto
  • NSE+ = cyto
148
Q

Plasma cell tumor: molecular markers & localization/expression?

A
  • MUM1/IRF4+ = N
  • CD18 +/- = PM
  • CD3- = PM
  • CD79a +/- = PM
  • PAX5- = N
149
Q

Rhabdo: molecular markers & localization/expression?

A
  • Vimentin + cyto
  • Desmin + = cyto
  • Myoglobulin +/- = cyto
  • SMA- (MyoD1 +/-, myogenein +/-) = N
  • myoglobulin typically late stage marker which may be negative in poorly differentiated tumors
  • MyoD1 and myogenin can be useful if undifferentiated
  • PTAH may highlight cross striations in skeletal m
150
Q

Sarcoma: molecular markers & localization/expression?

A
  • Vimentin +
  • Cytokeratin -
  • both cyto
151
Q

Synovial cell sarcoma: molecular markers & localization/expression?

A
  • Vimentin + = cyto
  • cytokeratin +/- = cyto
  • CD18- = PM
152
Q

Thyroid tumors (follicular epithelial origin): molecular markers & localization/expression?

A
  • Thyroglobulin + = cyto
  • TTF1+ = N
  • Calcitonin- = cyto
  • Chromagranin A-
  • Synaptophysin _
  • NSE -
153
Q

Thyroid tumors (C-cell/parafollicular cell origin - medullary): molecular markers & localization/expression?

A
  • Thyroglobulin - = cyto
  • TTF1+ = N
  • Calcitonin+
  • ChromograninA+
  • Syntaptophysin+
  • NSE+

Onco boards 2024 (17 decks)

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