Neoplasia III Flashcards
What are the 6 ways that neoplastic cells may behave badly?
- expansion
- tissue injury
- pain
- Invasion
- metastatis
- secretion (paraneoplastic syndromes)
What is the behaviour of hyper plastic cells? Cellular differentiation: Mitotic activity: Rate of growth: Necrosis: Tissue demarcation: Heterogeneity: Aneuploidy: Paraneoplastic syndromes: Propensity to progress if not removed: Recurrence after removal:
Cellular differentiation: Normal gradient, cells look normal. Mitotic activity: Variable, usually low Rate of growth: Reversible Necrosis: None Tissue demarcation: Blended into normal Heterogeneity: None Aneuploidy: None Paraneoplastic syndromes: None Propensity to progress if not removed: None Recurrence after removal: None
What is the behaviour of benign cells? Cellular differentiation: Mitotic activity: Rate of growth: Necrosis: Tissue demarcation: Heterogeneity: Aneuploidy: Paraneoplastic syndromes: Propensity to progress if not removed: Recurrence after removal:
Cellular differentiation: Usually well differentiated
Mitotic activity: Usually low
Rate of growth: Slow, irreversible
Necrosis: Usually minimal
Tissue demarcation: Expansive, discrete (encapsulated, exophytic, etc) - push around tissue
Heterogeneity: Minimal
Aneuploidy: Low
Paraneoplastic syndromes: Variable
Propensity to progress if not removed: Low
Recurrence after removal: Rare, depends on resectability
What is the behaviour of malignant cells? Cellular differentiation: Mitotic activity: Rate of growth: Necrosis: Tissue demarcation: Heterogeneity: Aneuploidy: Paraneoplastic syndromes: Propensity to progress if not removed: Recurrence after removal:
Cellular differentiation: Poorly differentiated, anaplastic, etc (hard to tell original cell type)
Mitotic activity: Often high
Rate of growth: Rapid, irreversible
Necrosis: Often high
Tissue demarcation: Poorly demarcated - locally infiltrative or invasive (hard to tell where neoplasm ends, cell begins)
Heterogeneity: More
Aneuploidy: More
Paraneoplastic syndromes: Variable
Propensity to progress if not removed: High
Recurrence after removal: Frequent
Define aneuploidy
Abnormal constituent of chromosomes
What is an example of expansive growth with neoplastic cells?
Benign tissue grows and damages tissue.
Brain compression by pituitary adenoma, airway obstruction by nasal tumour.
What is an example of how a neoplastic mass can cause local injury and pain?
Bone lysis/fracture. Osteosarcoma in distal femur of dog.
What is an example of how a neoplastic mass can cause local injury?
Ulceration, infection, hemorrhages, nerve damage, restricted motion. Sarcoid in horse, soft tissue sarcoma in dog.
What is an example of how a neoplastic mass can cause invasion and local spread?
Oral squamous cell carcinoma. Starts somewhere and invades somewhere else.
What is the phenotype of epithelial cells?
Cell adhesion to tight junctions and basement membrane. Cells transition back to epithelial after they have moved and invaded.
What is the phenotype of mesenchymal cells?
Less cell-cell tight junctions, less contact inhibition (grow in pile), more extracellular matrix adhesion, protease expression (how invade, destroy).
What is an example of metastasis?
Malignant mammary carcinoma in cat, secondary in lymphatics (carcinoma cells destroying lymphoid structures).
What is the difference between primary and secondary tumours?
The primary site is the site of origin and the secondary site is that of metastasis. With prostate carcinoma in the bone, the tumour has metastasized to the bone from the prostate so the bone is secondary and the prostate is primary.
What is hematogenous spread?
Spread of cancer through blood vessels. Eg metastatic carcinoma from gut to liver via portal vein. Hematogenous metastases in lung.
What is lymphatic spread?
Spread of cancer via lymph nodes. Eg mammary tumour in axillary lymph node.
What is the seed and soil/fertile soil concept of tumour metastases?
While many cells enter the lymphatics or blood, very few are able to succeed in growing in the places they reach.
Cells need:
-ability to detach from primary mass
-ability to invade local storm/parenchyma
-ability to enter a blood vessel (intravasate)
-ability to survive in circulation
-arrest in vessel or ability to adhere to endothelium
-ability to exit vessel (extravasate)
-ability to survive in new location by adapting to new environment
-ability to proliferate in new environment, angiogenesis
What is the problem with scar tissue in neoplasms?
Some tumour cells secrete growth factors like TGF B that induce fibrosis - tumours are hard and scarred/scirrhous.
What are paraneoplastic syndromes?
Some tumours produce excess amounts of functional products in an unregulated manner.
Eg pituitary adenoma in a horse with cushings. Benign but make dysfunctional products.
What is paraneoplastic hypercalcemia?
Some tumour cells release parathyroid hormone or another functionally related cytokine that also mobilizes calcium from the bone (eg anal sac adenocarcinomas). Leads to increased blood calcium and bone resorption.
What are the mechanisms of harmful neoplastic behaviour?
- activated oncogenes increase cell proliferation or inhibit cell death
- Increased secretion of functional molecules can adversely affect other cells (eg paraneoplastic syndromes)
- Increased secretion of matrix proteinases enables local tissue invasion
- Increased expression of growth factors enables neovascularization (angiogenesis), extracellular matrix and fibrotic (scirrhous) storm
- Increased expression of cell adhesion molecules enables metastatic adhesion
- Increased resistance to drugs or immune factors increases ability of cells to survive
- activation of telomerase expression prevents replicative senescence (cells become immortalized)
What is involved in the molecular basis of cancer treatment?
- signal pathway inhibition
- early detection markers
- targeting to inhibit adhesion
- Inhibition of angiogenesis
- antiproteases to inhibit invasion
- neutralize secretion
- Induce apoptosis to prevent survival
- block oncogenes to prevent proliferation
What is angiogenesis? Give an example
New blood vessels, required for neoplasms to increase in size. Without these, there will be zones of necrosis in the middle surrounded by fleshy healthy zone of tumour.
What do angiogenic growth factors do?
Recruit new blood vessels into the neoplasm to help grow, provide oxygen, get rid of waste. Basic fibroblast growth factor (bFGF) binds to heparin. VEGFs (vascular endothelial growth factor) are released from parenchymal cells.
What does the target appearance mean in a cell re: angiogenesis?
No good blood supply in middle, necrotic
What does sutent (sunitinib) do?
Inhibits angiogenesis by limiting the vessel growth to a certain size. Inhibits VEGF and VEGFR.
What are the 6 hallmarks of cancer?
- sustaining proliferative signalling
- evading growth suppressors
- activating invasion and metastasis
- enabling replicative immortality
- Inducing angiogenesis
- resisting cell death
What are the 2 emerging hallmarks of cancer?
- deregulating cellular energetics (altered metabolism, dealing with hypoxia)
- avoiding immune destruction
What are the 2 enabling characteristics of cancer?
- genome instability and mutation
- tumour promoting inflammation
What are the names of the 2 molecular defects in neoplasms?
Oncogenes and tumour suppressor genes
What is the role of oncogenes in cancer?
They are activated in cancer.
- mutated genes that produce proteins with increased growth stimulatory or cell survival functions (eg divide when they shouldn’t)
- mutations increase cell proliferation or survival
What is the role of tumour suppressor genes in cancer?
These are inactivated in cancers.
-normal genes that produce proteins involved in genomic stability and apoptosis, or that counteract effects of oncogenes
Tumour suppressor gene defects increase genomic instability
What role do receptors have in cancer?
Receptor control of gene expression is altered in cancer. Eg, c-kit (stem cell growth factor receptor)
-making too much membrane receptor -> downstream activity -> cells divide when they shouldn’t
What is the normal sequence of receptors and growth factors binding?
Growth factors bind to membrane receptors bind to signal transducers transduce transcription factors bind to response elements lead to gene expression.
What are the functions of tumour suppressor genes normally?
- cell cycle checkpoints (p53, p21, p16)
- Initiation of apoptosis after DNA damage (p53)
- DNA repair (mismatch, BRCA1, BRCA2)
- neutralize receptor kinase signalling (PTEN)
- regulation of cell to cell contact (cadherins)
Give some examples of genes that are defective in many cancers
p53, p21 and other checkpoint, DNA repair and apoptosis genes
What are DNA mismatch repair defects?
Inherited susceptibility to colon polyps and cancers in people with loss of function of DNA repair factors.
What is loss of heterozygosity?
In varied inherited susceptibilities, individuals are born heterozygous for one suppressor gene allele (eg one defective p53, one normal)
-cells that lose the remaining good copy are more prone to mutate and progress to malignancy
What is PTEN?
A tumour suppressor that when active, stops cells from dividing as much. Involved in neutralizing the effects of receptor kinases. PTEN positive is longer survival.
What are some oncogene examples that are mutated or increase?
NRAs, Ckit, MET, EGFR
What are some examples of tumour suppressor genes?
p53, p16, PTEN
True or false: it is important to detect cancer cells/masses early and resect them
True, find them early with imaging, biomarkers and remove them before they progress.
What are the steps involved in carcinogenesis in the colon?
Normal -> Focal hyperplasia -> benign -> malignant
