Cancer Flashcards
(110 cards)
0
Q
Squamous metaplastic cells? what kind of cancer does this lead to?
A
Endocervical, airway, urothelium
glandular/columnar –> squamous
Squamous cell carcinoma
1
Q
Glandular metaplastic cells? what kind of cancer does this lead to?
A
Barrett’s esophagitis (squamous –> columnar, goblet)
Adenocarcinoma
2
Q
Normal squamous epithelium?
A
skin, oral cavity, cervix
3
Q
Normal glandular epithlium?
A
Endocrine/exocrine, resp tract, GI tract/system, prostate/ovaries/uterus/breast
4
Q
How to characterize severity of dysplasia?
A
low–> high grade depending on thickness of epithelial invasion
5
Q
What is carcinoma in situ?
A
full thickness dysplasia (has not yet invaded BM)
6
Q
3 types of epithelial neoplasms
A
polyp- protrusion; sessile v pedunculated (mushroom)
papillary- fingers w fibrovascular core (ex. warts)
cystic- fluid filled; multilocular and unilocular
7
Q
Unique path features of squamous cell carcinoma
A
- intercelllular bridges
- keratinization (wholres, pearls, dyskeratotic; keratin antibody 5,6 will stain brown)
8
Q
Unique path features of adenocarcinoma?
A
Variable patterns depending on differentiation
Good differentiation- acinar, glandular
Poor differentiation- nests, sheets, trabecular, signet ring, cords
9
Q
What is a sarcoma?
A
mesenchymal tumor
10
Q
Cancer of smooth muscle tissue? histo?
A
leiomyeosarcoma
cells no longer spindle shaped
11
Q
Cancer of cartilage? histo?
A
chondrosarcoma
produces hyalin matrix; multiple cells per lacunae; pleomorphism
12
Q
Leukemia v lymphoma?
A
Leukemia: bone marrow cells
Lymphoma: cells of lymphoid tiissue (anywhere, B and T cells)
13
Q
Myeloma?
A
Type of lymphoma?
cancer of plasma B cells
14
Q
Path of lymphomas?
A
Loss of germinal centers (germinal center is hypocrhomatic cookie)
15
Q
Types of GOF mutation that –> cancer?
A
- point mutation
- copy number gain (amplification); detect via FISH
- chromosomal rearrangementf: regulatory region next to coding region for growth
16
Q
Examples of copy number gain –> cancer?
A
MYCN gene (TF): often amplified in neuroblastomas (common in kids) (requries more aggressive treatment)
HER2 amplification (EGF receptor 2) –> worse prognosis but herceptin is target
17
Q
MYCN gene mutation role in cancer?
A
MYCN codes for TF; often amplified in neuroblastomas
18
Q
Herceptin?
A
Targets EGF receptor 2 which is amplified in HER2 amplification mutations –> better prognosis
19
Q
Example of chromosomal rearrangement –> cancer?
A
Leukemias:
- Chronic myeloid leukemia (CML)- philly chromosome t9,22 (9 codes for ABL tyrosine kinase; 22 is regulatory) –> 3 different leukemias depending on length
- Burkitt’s lymphoma -cmyc related
20
Q
RET gene in cancer
A
GOF –> increase express receptor tyrosine kianse –> kinase signal cascade
–> multiple endocrine neoplasia type 2 (MEN2)
21
Q
MEN2 clinical features
A
MTC (medullary thyroid carcinoma)
pheochromocytoma- neuroendocrine tumor
hyperparathyroidism (HPT)
22
Q
MEN2A v MEN2B
A
MEN2A- GOF in extracellular domain (disulfiide bond) –> constitutive activation
MEN2B- GOF in intracellular domain –> consitiitutive activation; earlier onset with developmental abnormalities
23
Q
Familial MTC
A
medullary thyroid carcinoma
from GOF in RET gene
thyroid produces calcitonin which counteracts PTH which inhibits Ca2+ absorption to intestins and bones (secreted to urine)
24
What treatment for RET gene GOF?
early thyroidectomy to prevent MTC
25
Mode of inheritance for LOF in tumor suppressor gene?
Autosomal dominant, but two hit theory
26
Retinoblastoma genetics?
LOF gene
| --> bilateral, multifocal tumors with earlier onset; also higher risk for secondary tumors later in life
27
Synchronous v metachronous tumors?
Synchronous- simultaneous multiple tumors in same tissue
| Metachronous- tumors at different times in same tissue
28
FAP
- clinical features
- Risk
- Genetics
- 1000s of polyps in colon in adolescence
- 100% cancer by 39
- LOF in APC gene (normally antogonist of wnt pathway with binds beta catenin transcription activator)
29
Subtypes of FAP
- clinical features
- genetics
1. attenuated FAP: 10-100 polyps; 40% have monoallelic APC mutaiton (dominant pedigree)
2. MUTYH associated polypsis (MAP): 10-100polyps; not knudson (recessive); base excision repair
30
Lynch syndrome affected genes
```
HNPCC
MSH2 (50%)
MLH1 (20%)
MSH6 (15%)
PMS2 (15%)
```
31
Lynch syndrome proteins?
MSH2/MSH6, MLH1/PMS2
Mismatch repair
MMR gene test to diagnose (cheap)
32
Lynch syndrome clinical features
80% risk for colorectal cancer
~15 adenamatous polyps
early onset colorectal cancer
other common cancers
33
Lynch syndrome inheritance?
Autosomal dominant (heterodimer) (knudson?)
34
Li-Fraumeni
- clinical features
- genetics
-100% risk for breast CA, 90% of some cancer type by 70
4Bs: breast, bone, blood, brain
-germline TP53 LOF; knudson dominant
35
TP53 gene mutation: role in cancer
seen in 50% of cancers
environmental factors often --> point mutations here
(ex. aflatoxin B1 in mold --> sporadic liver CA)
Li-fraumeni
36
HBOC syndrome
| -genetics
germline LOF mutation in BRCA1/2
DNA break repair
Knudson dominant
37
Fanconi anemia
- genetics
- clinical features
- biallelic LOF in FANCD1 (FANCD1=BRCA2) (9 subunits, one must be in subunit A)
- short stature, malformation in radial arm, bone marrow failure by 15
38
Ataxia telangiesctasia:
- genetics
- clinical features
- bialllelic LOF in ATM protein (which signals BRCA1/2); detects ds breaks
- increased risk for blood cancers
39
3 steps of carcinogenesis
1. initiation
2. promotion
3. progression
40
Endogenous intiators of carcinogenesis?
Depurination (kick out A or G)
Damination (C--> U)
ROS
41
Exogenous initiators of carcinogenesis?
1. alkylating agents
2. UV radiation
3. Viral infection
42
Examples of alkylating agent initiators? (3)
polycyclic hydrocarbons, nitrosamines (in dyes), aflatoxin (--> TP53 mutation--> liver cancer)
43
2 types of UV radiation and mechanism of UV radiation for both
1. UVB--> DNA photoadducts (CC-->TT) --> apoptosis dysregulation (via inact p53, act EGFR/COX2)
2. UVA--> oxidative reaction
44
Xeroderma pigmentosa
disorder of DNA nT excision repair
| sensitivity to UVB
45
HPV virus types (3)
```
Benign (warts only)
Low risk (dysplasia): 6, 11
High risk (85% squamous carcinoma): 16, 18
```
46
Path features of HPV warts
- papillary
- hyperkeratinosis (keratin apical) with parakeratinosis (presence of nuclei in keratin)
- Acanthosis (thickened epithelium)
- Koilocytosis (nuclei in caves with thickened cytoplasmic ring)
47
Gradient from normal to invasive SqCCA in cervical cancer (histo)
LSIL (CN-1): koilocytes present, mostly mature squamous cells (requires colposcopy to confirm, differentiate between CN2/3)
HSIL (CN-2): polarity present; no koilocytes
HSIL (CN-3): no polarity, no koilocytes
iSqCCA: invasion through stroma
48
HPV screen (how frequently?)/diagnosis
- Pap test w cytology- high specificity, low sensitivity; every 3yrs (21-29), cytology + HPV testing every 5yrs (30-65)
- diagnosis with colposcopy
49
Describe HPV (virus), including proteins it codes for
```
non-envelop; dsDNA
spread by skin
40% of STDs
codes for E6 and E7 protein (E6 is lower risk)
(E6 inhibits p53; E7 inhibits p21)
```
50
Describe the HPV vaccine
capsid with virus like particles (VLPs)
Quadrivalent (6, 11, 16, 18) vs bivalent
recommended before sex
dose 1, wait 2 months, dose 2, wait 4 months
51
Epstein barr virus causes what cancer?
Burkitt's lymphoma (proteins that upregulate c-myc) (predisppose to rearrangement)
52
HepB causes what cancer? mechanism?
hepatocellular carcinoma
| binds p53 and causes liver damage that promotes hyperpplasia
53
HHV8 virus --> what cancer?
Kaposi's sarcoma and lymphomas, HIV patients
54
HTLV-1 virus --> what cancer?
leukemia
common in japan and carribbean
targets CD4 T cells
55
Lab model of promoter?
TPA (phorbol ester)
56
Promoters in breast and prostate cancer?
estrogen, testosterone
57
What is progression?
second irreversile gene mutation that --> malignancy
58
Describe steps of morphogenesis via inflammation
Initiation - ROS (will alter G so that it pairs with A or C)
| Promotion- GFs, cytokines, PGE2
59
3 ways of metastasis
1. lymphatics- carcinomas
2. blood vessels- sarcomas (will --> liver and lungs)
3. Mesothelial surfaces- ovarian and GI carcinomas (inoperable)
60
Prognosis for tumor contained in capsule?
probably benign
61
Prognosis for expansile/pushing tumor?
benign ("balloon-llike")
62
Prognosis for infiltrative tumor?
Malignant
63
Histo indicators of proliferation?
mitotic spindles
Ki67 stain shows proliferatin cells
more apoptotic cells with frgamented nuclei
64
Tumor specific v tumor associated antigen?
specific- only expressed on cancer cells
| associated- higher expression on cancer cells
65
Cancer cells are usually killed by what immune cells? how?
NK cells via MIC
66
Ways that cancer evades immune response (4)
1. Downregulate MHC-1 (evades CD8 T cells)
2. Downregulate tumor antigen (evade CD8 T cells)
3. No costimulatory moleccule expression (B7) (no costim for APC activation)
4. produce anti-inflammatoyr cytokines (ex. TGF beta: normally inhibits proliferation and lytic CD8 granules, activates Treg)
67
Uses for monoclonal antibodies in cancer?
1. recognize size and location of metastases
2. Toxin conjugate (ex. Gemtuzumab- antiCD33 expressed on myeloid leukemia)
3. Radionuclide conjugate (ex. Ibritumomab/tositumomab- targets CD20 for non-hodgkins lymphoma)
68
Types of chemotherapy
CCS (cell cycle specific) and CCNS (cell cycle nonspecific)
69
Antimetabolites?
CCS chemotherapy
| targets enzymes of S phase
70
MTX
Methotrexate
CCS chemotherapy
anti-metabolite:targets enzymes of S phase
reduces folic acid to folate --> shut down DNA/RNA synthesis (cant make purine or thymidine)
71
5-fluoruracil
CCS chemotherapy
anti-metabolite:targets enzymes of S phase
pyrimidine analogue
72
Cytosine arabinoside
CCS chemotherapy
anti-metabolite:targets enzymes of S phase
cytidine analogue
73
Mercaptopurine, thioguanine
CCS chemotherapy
anti-metabolite:targets enzymes of S phase
purine analogue
74
Vinca alkaloids
```
CCS chemotherapy
destabilizes microtubules (M phase)
```
75
Vincristine
CCS chemotherapy
Vinca alkaloid: destabilizes microtubules (M phase)
binds free tubulin (aggregates) --> depolym of microtubules
effective for childhood leukemia
madagascar flower
76
What chemotherapy option is effective for childhood leukemia?
Vincristine
77
Taxanes
```
CCS chemotherapy
hyperstabilizes microtubules (M phase)
```
78
Paclitazel
CCS chemotherapy
Taxane: destabilizes microtubules (M phase)
from tree bark
79
Epipodyphylotoxins
CCS chemotherapy
inhibits topoisomerase II (G2)
forms complex between DNA/isomerase/drug --> inactivation
80
Etoposide (VP150)
CCS chemotherapy
Epipodophylotoxin- inhibits topoisomerase II (G2)
forms complex between DNA/isomerase/drug --> inactivation
81
Teniposide
CCS chemotherapy
Epipodophylotoxin-inhibits topoisomerase II (G2)
forms complex between DNA/isomerase/drug --> inactivation
82
Campothecin
inhibits topoisomerase I (G1? or 2?)
| normallly TOPOI reversibly breaks ss DNA to relieve strain
83
Types of CCNS agents? (3)
Antibiotics
Alkylating agents
Platinum coordination complexes
84
Anthracyclins
- mechanism
- risks
CCNS
antibiotic
inserts to DNA --> ss/ds breaks
can only take lifetime max b/c cardiomyopathy risk
85
Bleomycins
- mechanism
- risks
CCNS
antibiotic
glycopeptide that induces DNA fragmentation--> accum in G2
not immunosuppresive (often paired with other drugs)
86
Nitrogen mustards
| example and mechanism
CCNS
Alkylating agent
ex. is mechlorethamine: covalent bind guanine
crosslinking
87
Nitrosureas
| -mechanism
CCNS
alkylating agent
covalent binding to DNA
88
Platinum coordination complex mechanism
reacts with DNA --> inter/intrastrand crosslinking
89
Nuclear hormone receptor therapy:
| -examples and mechanisms
Molecularly targeted therapy
Acts at receptor --> TF in nucleus
SERM- (selective estrogen receptor modulator)- breast cancer, ER antagonist (ex. Tamoxifen)
SARM- (androgen) (ex. bicalutamide)
90
Kinase targeting
| -example? problem with the drug?
Molecularly targeted therapy
- Gleevac: inhibits ABL kinase of philly chromosome rearrangmenet --> cell apoptosis
- relapse due to cancer mutation
91
Bicalutamide?
SARM- androgen receptor modulator
| nuclear homrone receptor therapy
92
Molecularly targeted therapy: targets?
hormone receptor
kinase
angiogenesis
proteasome blocking
93
Targeting angiogeneis for cancer:
| Pathway to target?
Molecularly targeted therapy
hypoxia --> HIF release (TF) --> express VEGF and FGF
-target VEGF or VEGFR
94
Bevacizumab (Avastin)
Molecularly targeted therapy
Angiogenesis target
VEGF antibody
95
Sunitinib (Sutent)
Molecularly targeted therapy
Angiogenesis inhibitor
VEGFR kinase inhibitor (small molecule)
96
Sorafinib (Nexavar)
Molecularly targeted therapy
Angiogenesis inhibitor
VEGFR/Raf kinase inhibitor (smalll molecule)
97
drugs "-mab"?
antibody
98
drugs "-nib"?
kinase inhibitor
99
3 ways vaccines can work against cancer?
Preventative (HPV)
Therapeutic
Activate immune system
100
Provenge
therapeutic use of vaccines
prostate CA
harvest APC, load prostate specific antigen, reinfuse into APC
101
Ipilimumab (Yervoy)
Antibody that activates immune system against cancer
targets CTLA-4 with antibodies, potentiates T cell activity
used for melanoma
102
Uses of biomarkers? (6)
risk assess, screen, diagnose, prognose, predict, monitor
103
Requirements for functional biomarker?
benefit > risk
reproducible
valid (specific and sensitive)
104
ER/PR biomarker?
immunohistochemistry
breast CA
predicts homrone therapy efficacy
105
HER2/NEU biomarker
immunohistochemistry or FISH
breast CA
predicts resonsee to perceptin (blocks EGF binding)
106
Gefitinib
blocks EGFR
| presence of EGFR predicts response drug; lung cancer
107
KRAS biomarker?
predict KRAS blocker response.
| mutation in KRAS (sometimes in colorectal CA) --> no response to EGFR inhibiting
108
High grade cancer histo?
higher grade - mitotic figures, nucleoli, pleomorphism
109
Staging criteria?
TNM- tumor extent, nodal metastasis, metastasis distant
| M1 = stage 4
