3.1 - 3.4 Neoplasia Flashcards
What are the three basic features of a neoplasm?
- Unregulated
- Irreversible
- Monoclonal
What is the marker to determine if a growth is monoclonal? How does this work?
G6PD
If 1:1 ratio is disrupted, then monoclonal expansion, since one cell would have only one isotype
How is the clonality of B cell determined?
Via Kappa or lambda Ig light chain secretions– if 3:1, this is polyclonal if normal. If this ratio disrupted, then Monoclonal lymphoma.
Are benign tumor monoclonal? Malignant?
Both are monoclonal
What, generally, are papillomas?
Outpouching of epithelial tissue, with a central fibrovascular core
Are tumors that have the potential to metastasize called benign or malignant?
Malignant
Benign Tumors derived from glands = ?
Adenomas
Benign Tumors derived from epithelial tissues (not glands) = ?
Papilloma
Malignant Tumors derived from glands = ?
Adenocarcinoma
Malignant Tumors derived from epithelial tissues (not glands) = ?
Papillary carcinoma
Benign moles are called what? Malignant?
Nevus
Melanoma
What is the malignant form of lipomas?
Liposarcoma
When is the -sarcoma suffix added?
To describe malignant mesenchymal tissue
When is the -oma suffix added?
Benign epithelial tissue
What is the name for a benign growth of lymphocytes?
Does not exist–always lymphoma/leukemia, which are malignant
What is the second leading cause of death in both children and adults?
CA
What are the three most common forms of CA by incidence?
- Breast/prostate
- Lung
- Colorectal
What are the three most common forms of CA by mortality?
- Lung
- Breast/prostate
- Colorectal
Does lung CA have a screening test?
Not really
How many cell divisions occur before CA symptoms arise?
30 divisions
What happens to the number of mutation with each division of CA cells? What is the consequence of this?
Increased– more malignant
What is the difference between dysplasia and CA?
Dysplasia is reversible, whilst cancer is not.
Where in the prostate does CA grow?
Posterior, peripheral part
What is the PAP smear screening for?
HPV 16 and 18
What does PSA and DRE screen for?
Prostate CA
Where are aflatoxins found, and what CA are they associated with?
Aspergillus on grains
Hepatocellular CA
Where are alkylating agents used, and what is the CA associated with them?
Used for chemotherapy
Leukemia/lymphoma associated
What are the CAs associated with EtOH use? (3)
- Squamous cell carcinoma of the oropharynx
- Pancreatic carcinoma
- Hepatocellular carcinoma
Where is arsenic found, and what CA is it associated with? (3)
-Present in cigarette smoke
- Squamous cell carcinoma of the skin
- Lung CA
- Angiosarcoma of the liver
What CAs are associated with asbestos?
Squamous cell carcinoma and mesothelioma
What CAs are associated with cigarette smoke?
Carcinoma of oropharynx
- esophagus
- lung
- kidney
- bladder
What is the chemical found in cigarette smoke that is particularly carcinogenic?
Polycyclic hydrocarbons
Where are nitrosamines found, and what CA are they associated with?
- Smoked foods
- Intestinal type of stomach carcinoma
Where is naphthylamine found, and what CA are they associated with?
Derived from cigarette smoke
Urothelial carcinoma of the bladder
Where is vinyl chloride found, and what CA is it associated with?
- Making PVC
- Angiosarcoma of the liver
What are the two types of people who classically develop Nasopharyngeal carcinoma?
- African male
- Young chinese male
What are the CAs caused by EBV? (3)
- Nasopharyngeal carcinoma
- Burkitt’s lymphoma
- CNS lymphoma
What is the CA associated with HHV-8?
Kaposi sarcoma
What is the CA associated with HBV and HCV?
Hepatocellular carcinoma
What are the CAs associated with HTLV-1?
Adult T cell leukemia/lymphoma
What are the high risk HPV virus strains? What CAs do they cause?
16, 18, 31, 33
Squamous cell carcinoma of the vulva, vagina, anus, cervix
Ionizing radiation produces what carcinogenic agents? What CAs is this associated with (3)?
Hydroxyl free radical generation
- AML
- CML
- papillary carcinoma of the thyroid
Non-ionizing radiation produces what? What is the most common source of this? What CAs is this associated with?
-Pyrimidine dimers
-UVB sunlight
-Basal cell carcinoma
Squamous cell carcinoma
Melanoma of the skin
What are the three systems (gene types) that can be disrupted by carcinogenic agents to cause a tumor?
- Protooncogenes
- Tumor suppressor genes
- Regulator of apoptosis
What are proto oncogenes?
genes that are essential for cell growth and differentiation, but can be mutated into oncogenes
What are the four categories of oncogenes?
- Growth factors
- Growth factor receptors
- Signal transducers
- Cell cycle regulators
What is the MOA of growth factors (i.e. what happens when it binds to a receptor)?
Binds to receptor, stimulates signal transducer, to start Cell cycle
What is the protein that drives the formation of an astrocytoma? How?
Overexpression of PDGFB by cell causes an (via an autocrine-like mechanism) increase in cell growth
ERBB2[HER2/Neu] is what? what happens to cause CA, and what specific CA does it cause?
- Epidermal GF receptor
- Amplification causes breast CA by increasing the receptor density and thus the response to normal amounts of GF
RET is what? What happens to cause CA, and what specific CA does it cause?
- Neural GF inhibitor
- Point mutation causes MEN2A/B receptor upregulation
specifically medullary carcinoma of the thyroid
KIT is what? what happens to cause CA, and what specific CA does it cause?
- Stem cell GF receptor
- Point mutation causes GI stromal tumor
Ras family gene is what? What happens to cause CA, and what specific CAs does it cause (3)?
- GTP binding protein (cell signalling molecule)
- Point mutation increases expression of nuclear proteins, to cause:
- carcinoma
- melanomas
- lymphomas
ABL is what? what happens to cause CA, and what specific CA does it cause?
- Y kinase signal transducers
- t(9:22) with BCR causes CML (and some ALL)
c-Myc is what? What translocation happens to cause CA, and what specific CA does it cause?
- transcription factor (nuclear regulator)
- t(8,14) causes Burkitt’s lymphoma
N-Myc is what? what happens to cause CA, and what specific CA does it cause?
Transcription factor
Amplification causes neuroblastoma
L-Myc is what? what happens to cause CA, and what specific CA does it cause?
Transcription factor
Amplification causes lung carcinoma
CCND1 (cyclin D1) is what? What translocation happens to cause CA, and what specific CA does it cause?
- Cyclin D1
- t(11;14) involving IgH causes mantle cell lymphoma
CDK4 is what? what happens to cause CA, and what specific CA does it cause?
- Cyclin dependent kinase
- Amplification causes Melanoma
What is the Philadelphia chromosome? What CA is it associated with?
t(9;22) with BCR.
CML and some types of ALL
What is the MOA behind burkitt’s lymphoma?
t(8;14) causes change of IgH gene with Myc gene in B cells, causing the overproduction of c-Myc
What is the MOA behind Mantle cell lymphoma?
Cyclin D1 (CCND1) gene on chr 8 is translated to chr 14 (IgH chain) in B cells, causing overexpression of CCND1
What is the function of Cyclin D1?
Allows cells to go from G1 to S phase
What are the two major tumor suppressor genes?
p53 and Rb
What is the function of p53?
“traffic cop” for cell between G1 and S phase–checks to make sure DNA is in order
What is the molecule that p53 calls in if there is DNA damage? What does this do?
BAX, which destroys BCL2 (this causes apoptosis)
p53 follows what model of DNA damage?
Two hit model
What is Li-Fraumeni syndrome
Germline mutation in one of the p53 genes, causing an increased propensity for developing carcinomas and sarcomas
What is the function of E2F? What is this protein bound to usually?
Allows for progression from G1 to S phase
usually bound and inhibited by Rb
What is the function of Rb?
Inhibits E2F protein, thereby inhibiting transition from G1 to S phase
Bilateral Rb is more likely caused by what (germline mutation or sporadic)? Unilateral?
Bilateral = Germline Unilateral = Sporadic
What is the function of Bcl2?
Stabilizes the mito membrane, so that cyt-c cannot be released
Bcl2 is overexpressed in what cancer? What translocations allows for this?
Follicular lymphoma t(14;18) moves Bcl2 to Ig heavy chain (14), resulting in increased Bcl2
What is the function of telomerase?
Preserves telomeres in CA cells
What are the two angiogenic factors that are upregulated in tumors to promote angiogenesis?
FGF
VEGF
Tumors create a lot of antigenic proteins. How do they avoid detection by the immune system?
Downregulate MHC I
True or false: immunodeficiency has no effect on the probability of getting CA
False–increases the risk
What is the function of E-cadherin? What is its role in CA?
Protein that attaches cells together.
Downregulation of this allows cell to metastasize
What are the two major proteins that comprise the basement membrane?
Collagen IV and laminin
What is the function of laminin in CA?
Allows tumors to attach to BM and destroy it via collagenases
Once in the ECM, tumors attach to what protein to migrate locally?
Fibronectin
What type of CA tends to spread via lymphatics?
Carcinomas
Hematogenous spread is characteristic of what type of CA?
Sarcomas
What are the four carcinomas that spread via hematogenous route?
- RCC
- Hepatocellular carcinoma
- Follicular carcinoma
- Choriocarcinoma
Seeding of body cavities is characteristic of what particular CA?
Ovarian CA (omental caking)
What is “omental caking”?
Local spread of ovarian CA into the omentum
What are the top three causes of death in adults?
- CV disease
- CA
- Cerebrovascular disease
What are the top three causes of death in children?
- Accidents
- Cancer
- Congenital defects
Who is classically affected with HHV-8 Kaposi’s sarcoma?
- Older eastern european males (skin)
- AIDS pts
- Transplant patients
What is the MOA and use of trastuzumab?
Antibody against the ERB2/Neu receptor on breast cancer
How does Ras become activated? Deactivated?
Binds to GTP
GAP cleaves the phosphate off of GTP
What is the treatment for CML?
Imatinib
What is the classic histological characteristics of Burkitt’s lymphomas?
starry sky with tingible body macrophages
What are the two regions that surround a follicle of a lymph node?
Mantle
Margin
Rb mutations increase the risk for what cancers?
Retinoblastomas, and osteosarcomas
Malignant or benign feature: slow growing
Benign
Malignant or benign feature: rapid growth
Malignant
Malignant or benign feature: poorly circumscribed
Malignant
Malignant or benign feature: infiltrative
Malignant
Malignant or benign feature: well circumscribed
Benign
Malignant or benign feature: mobile
Benign
Malignant or benign feature: fixed to surrounding tissues
Malignant
What is the only way to determine if a mass is cancer?
Bx
Malignant or benign feature: organized growth
Benign
Malignant or benign feature: uniform nuclei
Benign
Malignant or benign feature: minimal mitotic activity
Benign
Malignant or benign feature: nuclear pleomorphism
Malignant
How does the nuclear: cytoplasmic ratio compare between malignant and benign tumors?
Malignant has high nuclear: cytoplasmic ratio, whereas the reverse is true for benign
What is the hyperchromasia that is characteristic of malignant cells?
Dark staining nuclei
What is the absolute distinguishing feature between malignant and benign tumors?
Metastatic potential
Keratin is found in what type of tissue?
Epithelium
Vimentin is found in what type of tissue?
Mesenchyme
Desmin is found in what type of tissue?
Muscle
GFAP is found in what type of tissue?
Neuroglial cells
Neurofilament is found in what type of tissue?
Neurons
PSA is found in what type of tissue?
Prostate
Estrogen receptors are found in what type of tissue?
Breasts
Thyroglobulin is found in what type of tissue?
Thyroid follicular cells
S100 is found in what type of tissue?
Melanoma
Chromogranin is found in what type of tissue?
Neuroendocrine cells
What are the three general uses of serum tumors markers?
- screening
- monitoring response to treatment
- Monitoring recurrence
What is involved in grading a tumor?
Looking at architectural and nuclear features to determine if well or poorly differentiated
What, generally, is staging?
Size and spread of the cancer
Which is more important: cancer grade, or stage
Stage
What are the components of the TNM staging? Which of these is the most important?
- Tumor size or depth of invasion
- N = nodes
- M = mets
