Pathogenesis of head and neck cancer (1) Flashcards
What isn’t included in the umbrella term head and neck cancer
thyroid and upper oesophagus
describe head and neck cancer
- cancer is not a single disease
- different types of head and neck cancer-vast majority are squamous cell carcinomas (SCC), arising from lining mucosa
- other carcinomas can also arise - salivary glands e.g. polymorphous adenocarcinoma, odontogenic epithelium e.g. ameloblastic carcinoma
- aetiology of most salivary gland tumours is unknown
- different tumours types behave in different ways
- not all malignant tumours are equally malignant
describe neoplasia
- genetic disease
- tumour cells breed true: ie. the progeny of tumour cells are tumour cells indicating inheritance of properties
- nearly all carcinogens are mutagens
- tumour cells usually show nuclear abnormalities
- altered DNA content (aneuploidy) is common in tumour cells
describe the multistep theory of carinogenesis evolved from animal studies of carcinogens
1) Inititation - DNA damage and mutation
2) Promotion - clonal expansion of abnormal cells leading to cancer
What are the components of a neoplasm?
- neoplastic cells
- blood vessels
- inflammatory cells
- macrophages
- lymphocytes
- polymorphs
- fibroblasts
- stroma
What are key elements in cancer development?
- Tumour growth
replication
escape from senescence
evasion of apoptosis
limitless replicative potential - Invasive growth
- Angiogenesis
- Metastasis
Describe tumour growth
Most tumours are monoclonal ie all the cells in a tumour appear to arise from one parent cell which has undergone a genetic change.
This is then passed on to all the progeny.
Tumour cells lack the normal control mechanisms thus the clone expands due to uncontrolled proliferation
describe invasive growth
- reduction in cell-cell adhesion
e.g. reduced/loss of E-cadherin - Invasion of basement membrane and stroma
tumour cell attaches to BM via integrins and matrix proteins tumour cells produce proteolytic enzymes e.g. collagenase, matrix metalloproteases which break up the matrix - Tumour cells need to be motile - extrude pseudopodia which attach to stromal proteins. Actin cytoskeleton enables movement
describe invasive growth (detailed)
- requires cell-cell adhesion and communication
- predominates in well differentiated carcinomas
- inner cells protected from immunological assault
- high levels of autocrine pro-migratory factors and of proteolytic enzymes
- heterogeneous sets of cells invade together
describe angiogenesis
- formation of new blood vessels
- usually under tight physiological control however control is lost in tumours - the angiogenic switch - development of rich blood supply around tumour
- vessels formed are abnormal
- new blood vessels formed by outgrowth of endothelial cells from post capillary venules into tumour mass
- critical step in progression of small localised tumour to a bigger one with metastatic potential
- stimulus is increased production of factors by tumour cells (VEGF, angiogenin)
inhibition of angiogenesis anticancer therapy area (anti-angiogenic drugs) - often a pre-requisite for tumour progression
- tumours vascularised to different extent
- tumours require less oxygen and metabolites than normal cells
- density of tumour microvasculature needs not correlate with prognosis
What are common sites of metastatic disease?
- regional lymph nodes
- liver
- lung
- bone
- brain
- skin
- unusual sites - think of renal cancer, thyroid cancer, melanoma
What are routes of metastasis ?
- Lymphatic - carcinoma
- Haematogenous - sarcoma
- across body cavities
- serous cavities
- meninges/ventricles/spinal canal
- direct implantation
describe metastasis
- tumour cells breach the basement membrane of vessel and enter vessel lumen
- tumour cells carried to site of metastasis
- bind to endothelial cells, penetrate BM, move out of vessel
- establishment of metastasis, cell proliferation, angiogenesis
- complex molecular interactions involved in these stages
