behaviour of tumours Flashcards
what is neoplasia?
an autonomous proliferation of cells with the loss of normal growth control
what is a tumour?
it is any swelling that can be benign or malignant
what is benign?
when there is no local invasion and no metastasis
what is malignant?
when there is local invasion and metastasis
what is hypertrophy and hyperplasia?
hypertrophy is an increase in individual cell size and hyperplasia is an increase in the number of cells
what is metaplasia?
it is the replacement of mature tissue types
what is dysplasia?
commonly it is an abnormality that indicative of the precursor change of malignancy
what is anaplasia?
failure to differentiate in malignancy
what is the AAA, BCSP, BSP and the CSP programmes?
the abdominal aortic aneurysm, bowel cancer, breast screening and cervical screening programme
what are the DES, FASP, IDPS, and NIPE programmes?
the diabetic eye, fetal abnormality, infectious diseases in pregnancy and newborn and infant physical examination programmes
what are the NBS, NHSP, SCT?
the newborn blood spot, newborn hearing screening and the sickle cell and thalassaemia programmes
what is the name for all programmes and how are they assessed?
the screening and quality assurance programmes
what are three characteristics imperative in tumour behaviour?
invasion, metastasis and angiogenesis
what is the difference between invasion and metastasis?
invasion is invading the adjacent normal tissue and destroying normal tissue whereas metastasis is when it spreads from the site of origin to distant sites and forms secondary tumours here
what is the result of metastasis and invasion?
can result in local disease forming a systemic disease
how do clinicians characterise the tumours?
using staging and grading
which cancer is unlikely to metastasise?
basal cell carcinoma
which cancer is very likely to metastasise?
lung cancer and 1/3 of breast
how do paediatric patients present?
majority will already have metastasised
what happens with metastasis in adults?
around half of all adult patients will metastasise
how does invasion occur?
there is increased motility, decreased adhesion, production of proteolytic enzymes and mechanical pressure
how to cells adhere to one another?
cell to cell adhesion molecules called cadherins
what happens if there is a mutation in E-cadherin?
there is the loss of cell to cell adhesion and contact inhibition
where else can cells adhere to?
the matrix through cell-matrix adhesion molecules
what are cell-matrix adhesion molecules and how can changes in these lead to motility changes?
integrins
changes in integrin expression can result in the decreased cell-matrix adhesion
what changes happen in epithelial cells in cancer?
epithelial cells are usually tightly connected, polarised and tethered
mesenchymal cells are loosely connected and able to migrate
in cancer epithelial cells with gain mesenchymal cell properties making them able to migrate and invade
what changes occur in ECM during caner?
in the ECM there are matrix metalloproteinases and in normal tissue regulation there is a balance between the matrix and the metalloproteins, with tissue inhibitors of metalloproteins. In cancer the balance tips as the inhibitors become more dense and therefore favours ECM breakdown meaning that there is local invasion
what role does mechanical pressure play in tumour formation?
the uncontrolled proliferation forms a mass, this puts pressure on vessels and results in occlusion and pressure atrophy. The tumour will spread along the lines of least resistance
what are examples of proteolytic enzymes in the ECM?
interstitial collagenases, gelatinases and stomolysins
what do stomolysins break down?
collagen type IV and proteoglycans
what do gelatinases break down?
collagen IV and gelatin
what do interstitial collagenases break down?
collagen types I, II and III
what is the issue with metastasis?
there is an unknown primary site and this metastasis is often the presenting tumour. The secondary tumour burden is often greater than that of the first
why does metastasis make it difficult to grade?
they occur at different stages of the natural history in different tumours - may occur early, or be a late relapse commonly
what are the main routes of metastasis?
canalicular
haematogenous
lymphatic
transcoelomic
what is meant by canalicular?
some tumours especially carcinomas will metastasise along anatomical canalicular spaces such as the urinary tract or the bile duct, the airways or the subarachnoid space
what is meant by lymphatic?
it spreads through local or distant lymph nodes
what cancers often spread haematogenously?
liver, brain, lung and bone
what is transcoelomic?
it is when there is metastasis across the peritoneal, pleural or pericardial cavities or the CSF
what is another way of tumour metastasis?
implantation - spillage of tumour during biopsy or surgery
how do carcinomas and sarcomas initially spread?
carcinoma through lymphatic and sarcoma through the blood
which cancers often result in bone metastasis?
breast, prostate (sclerotic), lung (lytic), kidney and thyroid
what cancer spreads through the transcoelomic route?
ovarian
where does lung cancer often spread to?
the adrenal and the brain
what is the mechanical hypothesis?
that metastasis is dictated by anatomy - liver metastasising to the GIT
what is the seed and soil hypothesis?
the spread can go anywhere but can only grow if the conditions are right - tissue environment is important as it influences the organ selectivity for metastases
what is the issue with metastatic cells?
they can remain dormant for years
what are the stages of metastasis?
detachment, invasion, adherence loss and extravasation, intravasation,, survival against the host defences, growth and angiogenesis
what is angiogenesis?
new vessel formation that is derived from existing vessels
which cells are we unsure about the role of but know that they are involved?
the bone marrow derived endothelial stem cells
what is the function of angiogenesis?
it has a role in healing and development and is essential if a metastases are to grow larger than 1-2cm
what are the inhibitors of angiogenesis?
thrombospondin, endostatin, canstatin, and ECM proteins
what promotes angiogenesis?
inflammatory cells producing TGFbeta, stromal cells producing PDGF and tumour cells producing promoters such as VEGF
what is staging and graded needed for?
research for comparison of therapies, prognosis - survival time and QoL, treatment
what is the stage?
how far along the tumour is = how advanced it is, i.e has it metastasised and to what extent
what is the grade?
how quickly to tumour is progressing and how aggressive it is - how differentiated is it and how different to the cells of origin is it
what do stage and grade allow us to determine?
if the cancer is the primary site or if it is a secondary tumour resulting from metastasis
how are tumours graded?
G1-4 which is near normal to undifferentiated
how is staging determined?
pre-invasive, early tumour, locally advanced, metastases - I-IV
TMN system
what is the TMN system?
it is tumour, metastasis and nodes - each can be clinical, radiological or pathological
what is T?
it is the size and or the extent of the tumour
what is M?
it is the presence and extent of distant metastases
what is N?
it is the presence and number of lymph node metastases
in breast cancer screening what does Ti-T4 mean?
Ti - in situ stage T1 - less than 2cm T2 - 2-5cm T3 >5cm T4 - involving the chest wall or skin
in breast cancer screening what is the N section?
N0 - no nodes
N1 - ipsilateral nodes
N2 - more than ipsilateral nodes
in breast cancer screening what is the M part?
M0 - no distant metastases
M1 - distant metastases
all parts of the TMN system are combined to make an overall stage. Describe the stages? List the treatments.
stage 0 - Tis - surgery only
stage 1 - T1, N0, M0 - RT, surgery
stage 2 - T1-2, N1 OR T3 - RT and surgery
stage 3 - T(any), N2 or T4 - chemo and surgery
stage 4 - T(any), N(any), M1 - chemo
where is there correlation is staging?
between staging and outcome
what system is used to stage CRC?
Duke’s ABCD
what is A and the survival rate for Duke’s?
invades into, but not through the bowel wall - >90% survival chance for 5 years
what is B and the survival rate for Duke’s?
B - invades through the bowel wall but with no lymph node involvement - 70% 5 year
what is C and the survival rate for Duke’s?
local lymph nodes are involved - 30% 5 year survival
what is D and the survival rate for Duke’s?
distant metastases - 5-10% 5 year survival
what is the differentiation level?
it is the grade - how much the tumour resembles it’s original form
who performs grading?
histopathologists and therefore it is subjective
what else is involved in grading?
nuclear pleomorphism and size, mitotic activity and necrosis
