Neoplasm Flashcards
How is neoplasia differentiated from hyperplasia and repair? How are benign tumors different from malignant? What are their different clinically features? How can you know if a tumor is benign or malignant?
Unregulated, irreversible, and monoclonal
Benign: remain localized and do not metastasize
Slow growing, well circumscribed, distinct, and mobile
Well differntiated: Organized growth, uniform nuclei, low N:C ratio, minimal mitotic activity, lack of invasion, no metastatic potential
Malignant: Invade locally and have the potential to metastasize.
Rapidly growing, poorly circumscribe, infiltrative, and fixed to surrounding tissues and local structures.
Poorly differentiated: Disorganized growth (loss of polarity) Nuclear polymorphism and hyperchromasia High N:C ratio High mitotic activity with atypical mitosis Invasion
Biopsy is required.
What does carcinoma imply? Sarcoma? Generally, how do CAs spread? Sarcomas? What is a hamartoma? Choristoma? What are benign epithelial tumors called? Malignant? Mesenchyme?
CA=epithelial origin
Sarcoma=mesenchyme
Hamartoma:Non-neoplastic, disorganized overgrowth of tissues in their own location
Choristoma: NOrmal tissue in a foreign location.
Benign: adenoma/papilloma
Malignant: adenocarcinoma, papillary CA
Benign:-oma
Malignant: -sarcoma
What are the most common cancers by incidence in adults? By mortality
breast/prostate
lung
colorectal
Lung
breast/prostate
colorectal
How is cancer formation initiated? What are some important categories of carcinogens? What are some key regulatory systems that allow for tumor promotion and progession?
Initiated by DNA damage of stem cells that overcome DNA repair mechanisms.
Carcinogens are agents that damage DNA (chemicals, oncogenic viruses, radiation)
Disrupted regulatory systems: proto-oncogenes, tumor suppressor genes, and regulators of apoptosis
What cancer do aflatoxins lead to? Alkylating agents? alcohol, arsenic, asbestos, cigarette smoke, nitrosamines, naphthylamine, vinyl chloride, nickel/chromium/beryllium/silica/radon? How do people become exposed to these things?
aflatoxins: HCC, aspergillus found in stored rice/grains
Alkylating agents: Leukemia/lymphoma, chemotherapy
alcohol: Squamous cell CA of oropharynx and upper esophagus, HCC
arsenic: Squam. cell CA of skin/lung cancer/angiosarcoma of the liver, Cigarette smoke
asbestos: Lung CA and mesothelioma,
cigarette smoke: CA of oropharynx, esophagus, lung, kidney, bladder, and pancreas, polycyclic hydrocarbons particularly bad
nitrosamines: stomach CA, smoked foods/Japan
naphthylamine: urothelial CA of bladder, cigarette smoke
vinyl chloride: angiosarcoma of liver, occupational exposure; used to make PVC.
nickel/chromium/beryllium/silica/radon: Lung cancer, occupational
What cancers are associated with EBV? HHV-8? HBV/HCV? HTLV-1? High risk HPV? H. pylori? Liver fluke? Schistosoma haematobium?
EBV: Nasopharyngeal CA, Burkitt lymphoma, and CNS lymphoma in AIDS
HHV-8: Kaposi sarcoma
HBV and HCV: HCC
HTLV-1: Adult T cell leukemia/lymphoma
High risk HPV: Squam cell CA of vulva, vagina, anus, and cervix; adenocarcinoma of the cervix.
H. pylori: Gastric AdenomCA and MALT lymphoma
Liver fluke: cholangioCA
Schistosoma haematobium: baldder cancer (squam. cell)
What cancers are associated with ionizing radiation (nuclear reactor accidents and radiotherapy)? What is the mechanism? Nonionizing radiation (UVB rays)? Mechanism?
Ionizing: AML, CML, and papillary CA of the thyroid, free radicals
Non: basal cell CA, Squamous cell CA, and melanoma of the skin, pyrimidine dimers (normally removed by restriction endonuclease)
What do protooncogenes do? What can happen if they’re mutated? What are five categories of protooncogenes and what do those categories do?
Essential for cell growth and differentiation
Mutation can lead to uncontrolled growth
Grwoth factors induce cellular growth
Growth Factor Receptors mediate signals from growth factors
Signal transducers relay activation to nucleus
Nuclear regulators
Cell cycle regulators mediate progression through the cell cycle (cyclin D/CDK4 complex phosphorylates proteins that drive the cell through the cell cycle)
Describe how the RAS gene family an lead to neoplasm.
Ras is associated with growth factor receptors inactive (GDP bound state)
Receptor binding causes GDP to be replaced by GTP which activates Ras
Ras sends growth signals to nucleus
Ras inactivates itself by converting GTP to GDP (GTPase activating protein)
Mutated ras inhibits activity of GTPase activ. protein, leading to more growth signals
What is PDGFB? What tumor does it lead to and how? Same question for ERBB2 (HER2/neu), RET, KIT, RAS, ABL, c-MYC, N-MYC, L-MYC, CCND1 (cyclin D1), and CDK4.
GROWTH FACTOR
PDGFB: platelet derived growth factor, overexpression leads to astrocytoma
GF RECEPTOR
ERBB2 (HER2/neu): epidermal growth factor, amplification leads to subset of breast CAs
RET: Neural growth factor receptor, MEN2A, MEN2B, and sporadic medullary CA of thyroid
KIT:Stem cell GFR, GIST
SIGNAL TRANSDUCERS
RAS: GTP-binding protein, CAs, melanomas, and lymphoma
ABL: Tyrosine kinase, (9;22) with BCR, CML and some types of ALL
NUCLEAR REGULATORS
c-MYC: transcription factor, (8;14) involving IgH, Burkitt
N-MYC: TF, amplification leads to neuroblastoma
L-MYC: TF, amplification leads to Lung CA (small cell)
CELL CYCLE REGULATORS
CCND1 (cyclin D1): cyclin, t(11;14) involving IgH, mantle cell lymphoma
CDK4: cyclin dependent kinase, melanoma
What are tumor suppressor genes? What does p53 do? What does it do when DNA is damaged? How? What must happen to the p53 gene for tumors to be formed? What is the germline mutation of p53, and what is the result? What does Rb do generally? How does it do it? How does its mutation lead to cancer? What must happen to the gene for tumor formation to occur? What is the clinical result of a sporadic mutation? germline? What are some other tumor suppressor genes (APC, BRCA1/2, DCC, DPC/SMAD4, TSC1/2, VHL, WT1/WT2) and what cancers are they associated with?
Tumor suppressor genes regulate cell growth and thus decrease the risk of tumor formation
p53 regulates progression of cell cycle form G1 to S phase
When DNA is damage, it slows the cell cycle and attempts repair. If repair isn’t possible, it induces apoptosis (upreg. BAX, which disrupts Bcl2 lead to cytochrome C leak)
Both copies of must be knocked out
Li-Fraumeni-germline mutation-multiple CAs and sarcomas
Rb also regulates progression from G1 to S
It holds E2F transcription factor which allows transition to S phase. When Rb is phosphorylated by Cyclin D1/CDK4 complex, it releases E2F
A mutation in Rb doesn’t allow it to hold E2F making growth uncontrolled
Both copies of genes must be knocked out.
Sporadic=unilateral retinoblastoma
germline=bilateral retinoblast and osteosarcoma
OTHERS
APC-CRC (FAP)
BRCA1/BRCA2-breast and ovarian cancer (DNA repair protein)
DCC-colon cancer
DPC4/SMAD4-pancreatic cancer
TSC1, TSC2-tuberous sclerosis
VHL-von hipple lindau disease and renal cell CA (hypoxia inducible factor 1a)
WT1/WT2-wilms tumor (nephroblastoma)
What do regulators of apoptosis do? What is an example? Explain how mutations of this gene lead to follicular lymphoma.
They normally prevent apoptosis unless a cell is damage in which case they promote it. (Bcl2)
In follicular lymphoma, Bcl2 is overexpressed making the mitochondrial membrane extra stable and preventing apoptosis.
B cells that would normally undergo apoptosis during somatic hypermutaiton in LN germinal center accumulate, leading to lymphoma.
How do tumors avoid cellular senescence? How do tumors achieve angiogenesis? How do they avoid immune surveillance?
NOrmally, telomeres shorten with serial cell divisions, resulting tin cellular senescence.
Tumor cells have increased telomerase, which is necessary for cell immortality.
They produce FGF and VEGF
Down regulate expression of MHC class I (abnormal proteins in tumor cells not detected) Immunodeficiency increases risk for cancer.
Explain the steps of tumor invason and spread.
Normally, epithelial tumor cells are attached by E-cadherin
E-cadherin is downregulated leading to dissociation of attached cells
Cells attach to laminin and destroy BM via collagenase
They attach to fibronectin in ECM and spread locally
They can metastasize by entering vascular/lymph spaces
What neoplasms spread via lymph? Where to? Which by Hematogenous spread? Which neoplasm seeds body cavities?
Carcinomas by lymph, spread to regional draining LNs
Hematogenously-sarcomas and some CAs Renal cell CA (renal vein) HCC (hepatic vein) Follicular CA of thyroid Choriocarcinoma
Ovarian CA (seeding), omental caking
