Neoplasia I h/o Flashcards
What’s a neoplasm?
“tumor”
benign or malignant cell proliferation
How can you look at a tumor and decide it’s benign vs. malignant?
Benign tumors generally have non-invasive margins and have a fibrous capsule of some sort
Malignant tumors have progressively infiltrative growth accompanied by destruction of surrounding tissue
What’s a carcinoma refer to?
Malignant neoplasm of epithelial cells
Common examples are lymph nodes, breast
What’s a Sarcoma?
Malignant neoplasm of mesenchyme-derived tissue
Hematogenous (lung or liver), bone, fat, muscle
What’s a Taratoma?
Mixed germ cell tumor
-has more than one germ cell layer. Can even have a combination of all 3 (endo, meso, ectoderm)
Pretty gross, can make hair and sebum and smell terrible
What’s a Hamartoma?
Mass of mature but disorganized tissue indigenous to its site
-not a neoplasm, just a developmental anomaly
What’s a Choristoma?
mass of normal tissue present outside it’s normal site
-not a neoplasm, just a developmental anomaly
What’s a Polyp?
Macroscopic projection above a mucosal surface
can be a bump or a nodule on top of a stalk
What’s the word that refers to a polyp on a stalk?
A pedunculated polyp
opposite would be sessile, or flat
What’s anaplasia?
Lack of visible differentiation of malignant tumors
-look like primitive unspecialized cells
What’s the difference between an anaplastic cell and a primitive unspecialized cell?
- Larger
- Higher nuclear/cytoplasm ratio
- varying in size and shape
- nuclear abnormalities (clumped chromatin, etc)
What’s desmoplasia?
formation of fibrous tissue as a result of injury
-Carcinomas commonly have dense fibrosis around them
What’s a “Carcinoma in situ?”
A tissue with the features of a malignant cell mass, but without visible invasion.
Looks like it’s capable of metastasizing, but not 100% certain
What are the most common causes of cancer death?
- Lung
- Breast (women), Prostate (men)
- Colon
What are the six hallmarks of cancer?
- Self sufficiency in growth signals
- Insensitivity to anti-growth signals
- Tissue invasion and metastasis
- Limitless replicative potential
- Sustained angiogenesis
- Evading apoptosis
What do tumor suppressor genes do?
Control cell proliferation
- One functional copy of a tumor suppressor gene is all that is needed to control cell proliferation
- Both copies of a tumor suppressor gene must be knocked out for neoplasm to occur
What’s an oncogene?
Genes that drive cell growth in cancer cells
What are common examples of tumor suppressor genes?
RB gene (retinoblastoma) p53 gene (many tumor types) APC/beta-catenin pathway (colon) NF-1 and NF-2 (neurofibromatosis) VHL gene
How does the tumor suppressor RB protein work?
- Binds up Transcription factor E2F and prevents it from being utilized
- If RB protein is phosphorylated by cyclins, it releases the E2F. E2F then drives proliferation
Where in the cell cycle does RB protein inhibit?
G1 phase
What’s the difference between a familial formation of retinoblastoma and a sporadic formation of a retinoblastoma?
One hit vs. two hits
- Familial mutation: child is born with one defective copy of tumor suppressor gene. Only takes one mutation to completely knock out the tumor suppressing gene capacity, resulting in tumor formation
- Sporadic formation: Child is born with two normal copies of tumor suppressor gene. Both copies must be knocked out for cancer to develop (two hit)
How does the APC tumor suppressor gene control intestinal stem cell proliferation?
WNT signalling pathway:
APC protein normally binds and degrades beta catenin (a TF factor that drives cell proliferation)
WNT protein binds cell receptor, creating a signaling pathway which breaks down APC protein. This releases beta catenin and cell proliferates
What kinds of cancers involve APC mutation?
All familial adenomatous polyposis cancers
~70% of sporadic colon cancers
How does p53 work?
“Guardian of the Genome”
p53 prevents the propagation of genetically damaged cells
-binds DNA and arrests cell cycle for repair
-If repair isn’t possible, p53 initiates apoptosis
Is the half life of p53 long or short?
Short ~20 min
Degraded by proteolysis
Is a non-functional p53 gene common in tumors?
70% of tumors have bi-allelic loss of p53 gene
What’s an example of how tumors can grow resistance to p53? (HPV example)
- Increase in MDM2
- E6 protein of HPV
- both degrade p53
T/F p53 is utilized in chemotherapy and radiation therapy
True
p53 mediates chemotherapy and radiation therapy
What would be the cause if a tumor did not respond to p53 mediated chemotherapy?
The tumor cells would probably have bi-allelic deletion of p53 gene
What’s the primary apoptosis gene?
BAX
What does the NF-1 protein do in tumor suppression?
NF-1 is another tumor suppressor gene
Neurofibromin (NF-1 gene product) activates GTPase, creating GDP.
GDP binds RAS on cell membranes, inactivating it (RAS longer transduces growth factor signals for proliferation)
What happens if there is an inherited mutation in NF-1?
Neurofibromatosis type I
-numerous benign neurofibromas due to second hit mutations
What does the VHL gene product do?
VHL=Von Hippel Lindau
VHL protein causes ubiquitination and degradation of hypoxia inducible transcription factor 1
Hypoxia inducible TF1 normally causes an increase in PDGF and VEGF tumor angiogenesis
What is the result of a germline mutation in the VHL gene?
Leads to kidney cancer, retinal angioma, other cancer types due to second hit mutations
What are some common Oncogenes?
HER2 (20% of lung cancers)
K-RAS (colon, lung, pancreas)
L-MYC (small cell lung cancer)
C-MYC (Burkitt lymphoma)
What is HER2 and how does it function as an oncogene?
HER2 is an Epidermal Growth Factor Receptor (EGFR) which is overexpressed in many breast cancers.
If HER2 gene is overexpressed, the tumor cell will take up much more EGF, which stimulates cell growth and proliferation
What are three agents used in treating HER2 -positive breast cancers?
Trastuzumab, lapatinib, pertuzumab
How does K-RAS function as an oncogene?
K-RAS codes for a GTPase bound to EGFR on the cytoplasmic side of the cell membrane.
When EGFR is bound by EGFs, KRAS-GTPase cleaves GTP into GDP which stimulates transcription factors to drive cell proliferation
tumors cause K-RAS to be constitutively on
T/F tumors with K-RAS mutation will respond to EGFR blocker therapy
False
Mutated K-RAS is always on, even if EGFR is inhibited
