Pathogenesis of head and neck cancer (1) Flashcards

1
Q

What isn’t included in the umbrella term head and neck cancer

A

thyroid and upper oesophagus

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2
Q

describe head and neck cancer

A
  • 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
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3
Q

describe neoplasia

A
  • 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
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4
Q

describe the multistep theory of carinogenesis evolved from animal studies of carcinogens

A

1) Inititation - DNA damage and mutation
2) Promotion - clonal expansion of abnormal cells leading to cancer

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5
Q

What are the components of a neoplasm?

A
  • neoplastic cells
  • blood vessels
  • inflammatory cells
  • macrophages
  • lymphocytes
  • polymorphs
  • fibroblasts
  • stroma
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6
Q

What are key elements in cancer development?

A
  • Tumour growth
    replication
    escape from senescence
    evasion of apoptosis
    limitless replicative potential
  • Invasive growth
  • Angiogenesis
  • Metastasis
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7
Q

Describe tumour growth

A

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

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8
Q

describe invasive growth

A
  • 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
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9
Q

describe invasive growth (detailed)

A
  • 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
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10
Q

describe angiogenesis

A
  • 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
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11
Q

What are common sites of metastatic disease?

A
  • regional lymph nodes
  • liver
  • lung
  • bone
  • brain
  • skin
  • unusual sites - think of renal cancer, thyroid cancer, melanoma
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12
Q

What are routes of metastasis ?

A
  • Lymphatic - carcinoma
  • Haematogenous - sarcoma
  • across body cavities
  • serous cavities
  • meninges/ventricles/spinal canal
  • direct implantation
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13
Q

describe metastasis

A
  • 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
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