Neoplasia Flashcards
(125 cards)
1
Q
nitrosamines = carcinogen assoc with
A
gastric cancer
2
Q
polycyclic aromatic hydrocarbons = carcinogen assoc with
A
bronchogenic carcinoma
3
Q
asbestos = carcinogen assoc with
A
- bronchogenic carcinoma, mesothelioma
4
Q
chromium and nickel = carcinogen assoc with
A
bronchogenic carcinoma
5
Q
arsenic = carcinogen assoc with
A
- squamous cell carcinomas of skin and lung
- angiosarcoma of liver
6
Q
vinyl chloride = carcinogen assoc with
A
angiosarcoma of liver
7
Q
aromatic amines and as dyes = carcinogen assoc with
A
hepatocellular carcinoma
8
Q
alkylating agents = carcinogen assoc with
A
leukemia, lymphoma, etc
9
Q
benzene = carcinogen assoc with
A
AML
10
Q
naphthylamine = carcinogen assoc with
A
bladder cancer (transitional cell)
11
Q
how do we screen for potential carcinogens
A
Ames test
12
Q
Hep B virus is associated with
A
hepatocellular carcinoma
13
Q
EBV is associated with
A
- burkitt lymphoma
- B cell lymphomas in immunosuppressed patients
- nasopharyngeal carcinoma (China)
14
Q
HPV is associated with
A
- benign squamous papillomas (warts - condyloma acuminatum)
- a variety of carcinomas (cervical, vulvar, vaginal, penile, anal
15
Q
Ultraviolet B sunlight carcinogenesis
A
- produces pyrimidine dimers in DNA –> transcriptional errors and mutations of oncogenes and TSG –> increases risk of skin cancer
16
Q
xeroderma pigmentosum
A
- AR
- defect in DNA repair
- pyrimidine dimers formed with UVB can’t be repaired –> skin cancer
17
Q
when are cells most sensitive to radiation
A
during mitosis or G2
18
Q
protooncogenes
A
- normal cellular genes involved with growth and cellular differentiation
- when protooncogenes get mutated–> oncogenes
- oncogenes are derived from protooncogenes, either by a change in gene sequence –> new product (oncoprotein) or a loss of gene regulation resulting in overexertion of a normal gene product
- oncogenes only need one hit to express symptoms (vs TSG need 2 hits)
19
Q
hst-1 and int-2
- tumor
- gene product
- MOA
A
- oncogenes
- tumor: cancer of stomach, breast, bladder, melanoma
- gene product: growth factors: fibroblast growth factor
- MOA: overexpression
20
Q
sis
- tumor
- gene product
- MOA
A
- oncogene
- tumor: astrocytoma
- gene product: platelet derived growth factor
- MOA: overexpression
21
Q
erb-B1
- tumor
- gene product
- MOA
A
- oncogene
- tumor: squamous cell carcinoma (SCC) of lung
- gene product: growth factor receptors: epidermal growth factor receptor
- MOA: overexpression
22
Q
erb-B2
- normal function
- tumor
- gene product
- MOA
A
- oncogene
- receptor synthesis
- tumor: breast, ovary, lung
- gene product: epidermal growth factor receptor
- MOA: Amplification (have more than 2 copies)
23
Q
erb-B3
- tumor
- gene product
- MOA
A
- oncogene
- tumor: breast
- gene product: epidermal growth factor receptor
- MOA: overexpression
24
Q
ret
- tumor
- gene product
- MOA
A
- oncogene; tyrosine kinase
- tumor: MEN II and III, familial thyroid (medullary) cancer
- gene product: glial neurotrophic factor receptor (S100+)
- MOA: point mutation
25
abl
- tumor
- gene product
- MOA
- oncogene, tyrosine kinase activity; Chromosome 22 = philadelphia gene
- tumor: CML, ALL (5%)
- gene product: signal transduction proteins: bcr-abl fusion protein with tyrosine kinase activity (--> always on)
- aka p210kD fusion protein
- MOA: translocation t(9;22)
- tyrosine kinase are signal transduction proteins --> fusion protein causes cells to grow/proliferate
- DOC: imatinib --> blocks ATP binding site on tyrosine kinase
26
ki-ras
- normal function
- tumor
- gene product
- MOA
- MC oncogene to be overexpressed
- GTP signal transduction (gene product = GTPase)
- tumor: lung, pancreas, colon; neurofibromas
- gene product: GTP binding protein (signal transduction)
- MOA: point mutation
27
c-myc
- tumor
- gene product
- MOA
- oncogene on Ch 8; normally fx = nuclear transcription factor
- tumor: burkitt lymphoma (kids)
- gene product: nuclear regulatory protein
- MOA: translocation t(8;14) --> overexpression
- promotes cellular proliferation:
- when associated with p53, leads to apoptosis and
- when associated with bcl-2 inhibits apoptosis
28
L-myc
- tumor
- gene product
- MOA
- oncogene on Ch 1
- tumor: small cell lung carcinoma
- gene product: nuclear regulatory protein (transcription factor)
- MOA: amplification
29
N-myc
- tumor
- gene product
- MOA
- oncogene
- tumor: neuroblastoma (if <18mo = better prognosis; if >18mo worse prognosis, spread)
- gene product: nuclear regulatory protein (transcription factor)
- MOA: amplification (2 = normal, the more copies you have the worse the prognosis)
30
bcl-1
- tumor
- gene product
- MOA
- oncogene
- tumor: mantle cell lymphoma
- gene product: cell cycle regulatory proteins: cyclin D protein
- MOA: translocation t(11;14)
31
CDK4
- tumor
- gene product
- MOA
- oncogene
- tumor: melanoma, glioblastomamultiforma (GBM)
- gene product: cyclin dependent kinase
- MOA: amplification
32
bcl-2
- function
- tumor
- gene product
- MOA
- oncogene: overexpression --> fountain of youth
- if doesn't die, accumulates mutations until eventually develops cancer
- tumor: follicular non hodgkins lymphoma (arises from B lymphocytes in LN)
- MOA: translocation t(14;18) causes overexpression of Bcl-2 protein product--> prevents apoptosis of B lymphocytes (never die) --> follicular lymphoma = MC malignant lymphoma affecting adults in US
- tumor genesis related to changes in regulation of apoptosis: normally bcl-2 prevents apoptosis, but here the bcl-2 regulator of apoptosis is overexpressed bc the translocation connects the immunoglobulin heavy chain gene on Ch14 (which turns on easily in B lymphocytes) to the bcl-2 gene on Ch 18
- -> this leads to a situation where lymphocytes fail to die as expected and instead produce a tumor
33
tumor suppressor genes
- encode proteins that regulate and suppress cell proliferation by inhibiting progression of the cell through the cell cycle
- need 2 hits to express symptoms aka to knock out the TSG (vs oncogenes only need one hit)
- 1st hit could be gremlin, 2nd hit = acquired
- MOA of TSG varies. Ex)
- p53 prevents a cell with damaged DNA from entering S-phase.
- Rb prevents the cell from entering S-phase until the appropriate growth signals are present
34
VHL
- function
- chromosome
- tumor
- TSG, normal protein product inhibits hypoxia inducible factor 1a
- chromosome: 3p25
- function: regulates nuclear transcription
- tumor: von hippel-lindau disease (bilateral renal cell carcinoma, pheochromocytoma, hemangioblastomas), renal cell carcinoma
35
WT-1
- function
- chromosome
- tumor
- TSG, regulates nuclear transcription
- chromosome: 11p13
- tumor: wilms tumor
- WT-1 is by PAX-6 so they're knocked out together--> WAGR syndrome: kid has aniridia look for films tumor
36
WT-2
- function
- chromosome
- tumor
- TSG, regulates nuclear transcription
- chromosome: 11p15
- tumor: wilms tumor
37
Rb
- chromosome
- function
- tumor
- TSG
- chromosome: 13q14 (13 looks like B)
- function: Inhibits E2F; blocks G1 to S phase of cell cycle
- tumor: retinoblastoma, osteosarcoma (sunburst, codmans triangle)
- MOA: "policeman of checkpoints"
- if have familial Rb have 40% chance of other tumor developing
- if familial type of RB: develops early, both eyes. born with 1 germline mutation and acquire point mutation.
- if sporadic (non-familial) type: both alleles inactivated in somatic mutation in one of the retinoblasts --> occurs later in life; unilateral.
- assoc with retinoblastoma, osteogenic sarcoma, breast cancer
38
p53
- function
- chromosome
- tumor
- TSG (TP53), MC knocked out in most cancers!!
- p53 activates p21, inhibits G1 to S phase, repairs DNA, activates BAX
- chromosome: 17p13.1
- tumor: Li fraumeni (Li looks like an upside down 17)
- lung, breast, colon, etc
- p53 tells Rb to stop cell and if no it lets cytochrome c out of mitochondria --> apoptosis
- p53 is often knocked out in malignant tumors
- p53 promotes apoptosis in mutated cells by stimulating bax synthesis.
39
BRCA-1
- chromosome
- function
- tumor
- TSG
- chromosome: 17q12-21
- function: regulates DNA repair
- tumor: hereditary breast, ovarian, pancreatic, colon and prostate cancers
- "there are 17 letters in angelina jolie-pitt"
40
BRCA-2
- chromosome
- function
- tumor
- TSG
- chromosome: 13q12-13
- function: regulates DNA repair
- tumor: hereditary breast cancer
41
APC
- chromosome
- function
- tumor
- TSG
- chromosome: 5q21 (5 letters in colon)
- function: prevents nuclear transcription
- negative regulator of β-catenin/WNT pathway
- tumor: Adenomatous Polyps and Colon cancer; FAP
42
DCC
- chromosome
- tumor
- TSG
- chromosome: 18q21
- tumor: colon cancer
43
NF-1
- chromosome
- tumor
- TSG; turns off ras
- chromosome: 17q11.2
- gene product: neurofibromin (Ras GTPase activating protein)
- tumor: neurofibromas, cafe au last spots, lisch nodules
44
NF-2
- chromosome
- tumor
- TSG
- chromosome: 22q12
- gene product: merlin (Schwannomin protein)
- tumor: schwannomas of acoustic nerve = acoustic neuromas, meningiomas
45
keratin
- normal tissue
- tumors
- intermediate filament
- normal tissue: all epithelial cells
- tumors: carcinomas
46
vimentin
- normal tissue
- tumors
- intermediate filament
- normal tissue: mesenchymal cells
- tumors: sarcomas
47
desmin
- normal tissue
- tumors
- intermediate filament
- normal tissue: muscle cells; actin also found in muscle
- tumors: uterine leiomyoma, rhabdomyosarcoma
48
neurofilament
- normal tissue
- tumors
- intermediate filament
- normal tissue: CNS and PNS neurons, neural crest derivatives
- tumors: pheochromocytoma, neuroblastoma
49
glial fibrillary acidic protein (GFAP)
- normal tissue
- tumors
- intermediate filament
- normal tissue: glial cells (i.e. astrocytes, oligodendrocytes, ependymal cells)
- tumors: astrocytomas, ependymomas
50
increased AFP in pregnant woman
neural tube defects
51
decreased AFP in pregnant woman
down syndrome
52
AFP: tumor marker for
hepatoma (HCC), nonseminomatous testicular germ cell tumors (yolk-sac --> fetal proteins)
53
β- hCG: tumor marker for
- trophoblastic tumors (mole), choriocarcinoma
| - from placental cells
54
calcitonin: tumor marker for
- used for medullary carcinoma of the thyroid
- c cells --> neural crest --> S100
- surrounded by amyloid
55
carcinoembryonic antigen (CEA) : tumor marker for
- Major associations: colorectal and pancreatic cancers
- minor associations: gastric, breast, medullary thyroid carcinomas
- CA15-3, CA-125, CA19-9
- Kaplan: carcinomas of the lung, pancreas, stomach, breast and colon (colorectal and pancreatic adenocarcinomas*)
56
CA-125: tumor marker for
malignant ovarian epithelial tumors (surface derived ovarian CA)
57
CA19-9: tumor marker for
malignant pancreatic adenocarcinoma
58
placental alkaline phosphatase: tumor marker for
seminoma
59
biopsy when PSA is >
- biopsy when PSA is >10
- normal: 0-4
- PSA increased in BPH and prostatitis
60
CA-15-3: tumor marker for
breast carcinoma
61
sarcoma
Sarcomas are tumors that arise from "mesenchymal" tissues such as bone, muscle, connective tissue, cartilage and fat.
- all sarcomas are vimentin +
62
carcinoma
- epithelial cell tumors that become malignant
- Most cancers (>90%) arise from "epithelial" tissues, such as the inside lining of the colon, breast, lung or prostate.
- usually affect older people.
- all carcinomas are keratin +
63
S100 + seen in
melanoma and neural tumors
64
ionizing radiation (ie hiroshima) puts you at risk for developing
- AML
| - papillary carcinoma of thyroid
65
familial Rb
- every cell in body has 1 Rb gene knocked out at birth
| - if get 2nd mutation --> bilateral Rb and osteogenicsarcoma
66
Li fraumeni syndrome
- every cell missing 1 p53 (has p53 mutation) at birth
- if get 2nd p53 mutation --> cancer all over body
- colon, prostate, breast, sarcoma, lymphoma, etc
67
S-100
- melanoma and cells that come from neural crest
68
these cancers spread via hematogenous spread
- most sarcomas
- renal cell carcinoma (bc of proximity to large renal vein)
- hepatocellular carcinoma (bc of the presence of the hepatic sinusoids)
- follicular carcinoma of thyroid
- choriocarcinoma (bc of its propensity to seek vessels
69
seeding of body cavities occurs commonly in
ovarian carcinoma
70
familial melanoma mutation
p16 (TSG) mutation on chromosome 9
71
dysplastic nevus syndrome
- multiple dysplastic nevi
- micro: cytological and architectural atypia
- AD
- CMM1 gene on Ch 1
- increased risk of developing malignant melanoma
72
TGF-β
- function
- cancers
- Function: inhibits G1 to S phase
| - associated cancer: pancreatic and colorectal cancers
73
LN:
- B cells are located in the
- T cells are located in the
- B cells are located in the Follicles of LN
| - T cells are located in the paracortex (around LN)
74
t(8;14)
burkitt's lymphoma
75
t(9;22)
CML (Chronic myelogenous leukemia)
76
t(14;18)
B cell follicular lymphoma
77
Lesch Nyhan Syndrome
- genetic mutation
- effect
- clinical symptoms
- X-linked Recessive
- enzyme deficiency: hypoxanthine - guanine phosphoribosyltransferase (HGPRT)
- normally involved in in salvaging the purines hypoxanthine and guanine
- clinical: MR, hyperuricemia (gout), self mutilation
78
Vit D resistant rickets
- genetic mutation
- effect
- clinical symptoms
- X-linked recessive
| - defects in renal and GI reabsorption of phosphates --> defective bone mineralization (i.e. osteomalacia)
79
Alport's Syndrome
- genetic mutation
- effect
- clinical symptoms
- X-linked recessive
| - hereditary glomerulonephritis w/ nerve deafness (see kidney)
80
hyperhomocystinemia
- inborn error of metabolism
- homocysteine levels: >100 micromol/L
- due to low folate and Vit B12 intake --> increased incidence of vascular disease
81
bence jones protein = tumor marker for
multiple myeloma, waldenstrom's macroglobulinemia
82
tonofilaments
- important EM finding in epithelial tumors
83
weibel palade bodies
important EM finding in angiosarcomas
84
neurosecretory granules
important EM finding in neuroendocrine tumors
85
birbeck granules
- important EM finding in histolytic tumor (i.e. histiocytosis X = CD-1 positive)
- looks like tennis racket
86
CD45
leukocyte malignancies (common leukocyte antigen)
87
neuroendocrine tumors are + for
S100 and neuron specific enolase (NSE)
88
cytokeratin is found in
carcinomas
89
EMA is found in
carcinomas (EMA= epiehtlial membrane antigen)
90
vimentin is found in
tumors of mesenchymal tissue
91
desmin is found in
muscle derived sarcomas
92
trousseau's is associated with
- pancreatic adenocarcinoma (bc excess mucin production)
| - aka superficial migratory thrombophlebitis
93
NBTE (nonbacterial thrombotic endocarditis) associated with
mucous secreting colon and pancreatic adenocarcinomas
94
hypertrophic osteoarthropathy
- clubbing of the nails with an underlying periosteal reaction of bone of distal phalanx that's associated with primary lung cancer (bronchogenic carcinoma)
95
eaton lambert syndrome
- myasthenia gravis like symptoms (i.e. muscle weakness)
- antibodies directed against calcium channel
- associated with small cell CA of lung
96
Cushing's syndrome
- increased cortisol --> cushing's syndrome (lemon on a stick appearance)
- ectopic ACTH release --> increased cortisol
- associated cancers = small cell cancer of lung, medullary carcinoma of thyroid
97
hyponatremia
- endocrinopathy
- associated cancer
- ectopic ADH release
| - associated with small cell cancer of lung
98
hypocalcemia
- endocrinopathy
- associated cancer
- calcitonin
| - associated with medullary carcinoma of thyroid
99
gynecomastia
- endocrinopathy
- associated cancer
- β-hCG
| - choriocarcinoma of testes
100
hypercalcinoma
- endocrinopathy (cause)
- associated cancer
- MC paraneoplastic syndrome
- malignancy accounts for 40% of all cases. Causes:
1. release of PTH related peptide (PTHrP) - metastasis to bone not necessary)
- in squamous cell carcinoma of lung and renal cell carcinoma
- labs: hypercalcemia and decreased serum PTH
2. osteolytic bony metastasis** (release of osteolytic factors PGE2, IL-1)
- seen in breast cancer
101
acanthiosis nigricans
associated with stomach carcinoma
102
prolactinoma
- secretes excess prolactin --> amenorrhea, infertitility and calactorrhea
- pituitary tumosr
103
somatotropic adenoma
- tumor secreting excess growth hormone --> gigantism in children and acromegaly in adults
104
adrenal adenoma
- increased cortisol --> Cushing's syndrome
- incrased mineralocorticoids --> Conn's syndrome
- increased sex hormone --> adrenogenital syndrome
105
granulosa theca cell tumor causes
hyperestrinism
106
sertoli/leydid cell tumor causes
excess androgen
107
cachexia is caused by
- TNF-α (aka cachectin)
| - suppresses appetite center in hypothalamus and increases mobilization of FA from adipocytes (increased catabolism)
108
right sided colorectal carcinoma causes what hematological association?
iron deficiency anemia
109
macrocytic anemia due to folate deficiency from rapid tumor growth is seen in
leukemias and lymphomas
110
chronic lymphocytic leukemia has what hematological association?
autoimmune hemolytic anemia
111
myelophthisic anemia =
anemia related to metastasis to BM
112
CDKN2A
- TSG
- p16, blocks G1 --> S phase
- seen in melanoma and pancreatic cancer
113
DPC4
- TSG Deleted in Pancreatic Cancer
| - aka SMAD4
114
ALK
- oncogene
- gene product: receptor tyrosine kinase
- associated neoplasm: lung adenocarcinoma
115
BRAF
- oncogene
- gene product: serine/threonine kinase
- assoc w: melanoma, non-hodgkin lymphoma, papillary thyroid carcinoma
116
c-kit
- oncogene
- gene product: cytokine receptor
- assoc w: GI stromal tumor (GIST)
117
α-fetoprotein
- associated cancers: hepatocellular carcinoma, hepatoblastoma, yolk sac tumor, mixed germ cell tumor
- normally made by fetus; transiently high in pregnancy
- high levels assoc with near tube and abdominal wall defects
- low levels assoc with Downs
118
β-HCG
- associated cancers: Hydatidiform moles, Choriocarcinomas, Gestational trophoblastic disease
- produced by synctiotrophoblasts of placenta
119
CA15-3
associated with breast cancer
120
calcitonin
associated with medullary thyroid carcinoma (alone and in MEN2A and MEN2B)
121
P-glycoprotein
- AKA multi drug resistance protein 1 (MDR1)
- pumps out toxins (including chemo)
- classically seen in adrenocortical carcinoma but also expressed by other cancer cells (colon, liver)
122
CA27-27
associated with breast cancer
123
polycythemia associated with
- increased EPO
| - RCC, HCC, hemangioblastoma, pheochromocytoma, leiomyoma
124
myasthenia gravis is associated with what cancer (as a paraneoplastic syndrome)
- thymoma
| - ab against postsynaptic ACh receptors at NMJ
125
lambert-eaton is associated with what cancer (as a paraneoplastic syndrome)
- small cell lung cancer
| - ab against presynaptic (P/Q type) calcium channels at NMJ
