tumour pathology week 6 Flashcards
what is aetiology
what causes disease
what is pathogenesis
how a disease develops and progresses
what is neoplasia
the uncontrolled, abnormal growth of cells or tissues in body
what is classification of tumours based on
- tissue of origin
- benign vs. malignant
nomenclature of epithelial tumours
glandular benign: adenoma malignant: adenocarcoma squamous benign: squamous papilloma malignant: squamous carcinoma
nomenclature of connective tissue tumours
bone benign = osteoma malignant = osteosarcoma fat benign = lipoma malignant - liposarcoma fibrous tissue benign = fibroma malignant = fibrosarcoma
nomenclature of tumours of blood cells
white blood cells
malignant = leukaemia
- no known benign tumours of WBC
- no known tumours of red blood cells
nomenclature of tumours of lymphoid tissue
malignant = lymphoma
- no known benign tumours of lymphoid tissue
nomenclature of tumours of melanocytes
benign = naevus malignant = melanoma
nomenclature of neural tissue
central nervous system = astrocytoma
peripheral nervous system = shwannoma
nomenclature of germ cells tumours
- germ cells (testes/ovaries)
- teratomas
- tumour can be composed of various tissue because they are stem cells
- ovarian teratomas usually benign
- testicular teratomas usually malignant
what are some features of benign tumours
- non-invasive growth pattern
- usually encapsulated
- no evidence of invasion
- no metastases
- cells similar to normal
- ‘well differentiated’
- function similar to normal tissue
- rarely cause death
what are some features of malignant tumours
- invasive growth pattern
- no capsule or capsule breached by tumour cells
- cells abnormal
- ‘poorly differentiated’
- loss of normal function
- often evidence of spread of cancer
- frequently cause death
what are some properties of cancer cells
- loss of tumour suppressor genes (BRCA1, Rb)
- gain of function of oncogenes (B-raf, cyclin D1)
- altered cellular function
- abnormal morphology
- cells capable of independent growth
what happens to cellular function in cancer
- loss of cell to cell adhesion
- altered cell to cell matrix adhesion
- production of tumour related proteins
what are tumour biomarkers
- any properties of cancer cells that can be exploited clinically
- Onco-foetal proteins (present in foetus, switched off post natal, switched on again in tumours), oncogenes, growth factors and receptors, immune checkpoint inhibitors
what are some examples of clinically useful predictive biomarkers
Kras = colorectal cancer Braf = melanoma EGFR = lung cancer PD-L1 = lung cancer Her2 = breast cancer, gastric cancer
what is morphology of cancer
- histology of cancer
- cellular and nuclear pleomorphism
- mitoses present and often abnormal
what is tumour growth a balance of
- cell growth and cell death
- angiogenesis and apoptosis
what is tumour angiogenesis
- new blood vessel formation by tumours
- required to sustain tumour growth
- provides route for release of tumour cells into circulation
- more blood vessels in a tumour = poorer prognosis
what is apoptosis
- mechanism of programmed single cell death
- active cell process
- regulates tumour growth
- involved in response to chemo and radio therapy
how does metastasis begin
- increased matrix degradation by proteolytic enzymes
- altered cell-to-cell and cell-to-matrix adhesion
what are the modes of spread of cancer
- local spread (spread into adjacent structures, invasion)
- lymphatic spread
- blood spread
- trans-coelomic spread (through body cavities)(lung, stomach, colon and ovary cancers)(e.g. pleural or peritoneal cavities)
what does site of metastasis depend on
- doesn’t depend on blood flow
- depends on both tumour and tissue related factors
- metastatic niche
what are some common sites of metastasis
- liver
- lung
- brain
- bone (axial skeleton)
- adrenal gland
- omentum(layer of adipose tissue in abdomen)/peritoneum(tissue that lines abdominal walls)
what are some uncommon sites of metastasis
- spleen
- kidney
- skeletal muscle
- heart
where do breast tumours normally metastasise to
bone
where does prostate cancer normally metastasise to
bone
where does colorectal cancer normally metastasise to
liver
where does ovarian cancer noramally metastasise to
omentum(layer of adipose tissue in abdomen)/peritoneum(tissue that lines abdomen)
what are the local effects of benign tumours
- pressure
- obstruction
what are the local effects of malignant tumours
- pressure
- obstruction
- tissue destruction - ulceration/infection
- bleeding - anaemia, haemorrhage
- pain - pressure on nerves, perineurial infiltration (tumour infiltrates along nerves), bone pain from pathological fractures
- effects of treatment
what are the systemic effects of malignant tumours
- weight loss - cancer cachexia
- secretion of hormones - normal (e.g. tumour in gland secreting), abnormal/inappropropriate (tissue that doesn’t normally secrete is secreting)
- paraneoplastic syndroms
- effects of treatment
what is dysplasia
- pre-malignant change
- earliest change in the process of malignancy that can be visualised
- identified in epithelium
- no invasion
- can progress to cancer
what are some features of dysplasia
- disorganisation of cells - increased nuclear size, increased mitotic activity, abnormal mitoses
- grading of dysplasia - high/low (high = more risk in shorter time)
- no invasion
an adenoma is what type of tumour
benign tumour of glandular epithelium
an adenocarcinoma is what type of tumour
malignant tumour of glandular epithelium
what are the phases of the cell cycle
- G1
- S
- G2
- mitosis
what can result in G1 arrest
- inadequate nutrient supply
- external stimulus lacking
- abnormal cell size
- DNA damage detected
what can result in G2 arrest
- abnormal cell size
- DNA damage detected
what can result in S phase arrest
DNA not replicated
what can result in M phase arrest
chromosome misalignment
how are cyclin-dependent kinases activated
by cyclins to form CDK/cyclin complex
what do CDK/cyclin complexes do
- different CDK/cyclin complexes operate at sequential stages of the cycle
- active CDK/cyclin complexes phosphorylate target proteins
- phosphorylation results in the activation/inactivation of these proteins
- substrates of these proteins regulate events in the next cycle phase
what does INK4A do in cell cycle
- is it a CDK inhibitor
- binds to CDK
- includes p16, p14
- p16INK4A arrests the cell cycle in G1
- p14 prevents p53 degradation
what is CIP/KIP
- CDK inhibitor
- includes p21, p27 and p57
- halt cell cycle in G1
- deactivate CDK/cyclin by binding
what does the retinoblastoma gene do
enodes a 110 kDa phosphoprotein (pRb) expressed in almost every human cell
what does pRb do
in the hypo-(non)-phosphorylated (active) state, pRb is active and carries out its role as tumour suppressor by binding to E2F (a signal for cell cycle activation) and therefore this inhibits the cell cycle
- when pRb is phosphorylated it loses affinity to E2F
what does p53 do
- in G1 if there is DNA damage p53 arrests cell cycle and induces repair and if that doesn’t work then apoptosis
what does mutated p53 do
does not arrest G1 or repair damaged DNA
what is intra-epithelial neoplasia
A condition in which abnormal cells are found on the surface of or in the tissue that lines an organ, such as the prostate, breast, or cervix.
what environmental agents can cause carcinogenesis
- chemicals
- radiation
- oncogenic viruses
what are genotoxins and what do they do
- chemical agents such as alkylating or oxidising agents or non-chemical agents such as UV light and ionising radiation
- they cause irreversible genetic damage or mutations by binding to DNA
what are tumour suppressor genes (anti-oncogenes)
- genes that protect a cell from forming cancers
- mutation causes loss of function
- follows ‘two hit hypothesis’ = tumour suppressor alleles are usually recessive, loss of both normal allelic copies gives rise to cancer
what type of genes are affected by inherited cancer syndromes
- tumour suppressor genes
- proto-oncogenes (help cells grow but mutation can cause it to be permanately turned on)
- mismatch repair genes (correct mismatched nucleotides
what are oncogenes activated by
- alteration of port-oncogene structure
- can be due to point mutation or chromosome re-arrangements and translocations
what do chemical carcinogens do
- react with DNA forming covalently bound products (DNA adducts)
- adduct formation can lead to activation of oncogenes and loss of anti-oncogenes
what are oncoviruses and what do they do
- viruses known to cause cancer in humans e.g. HPV, hep B
Either: - virus genome inserts near port-oncogene causing over expression
- virus directly inserts an oncogene into host DNA causing cell division
