L22 - Behaviour of tumours Flashcards
what is neoplasia?
● An autonomous proliferation of cells
● Loss of normal growth control
● Tumour: literally any swelling
what does benign mean?
No local invasion; no metastasis
what does malignant mean?
Local invasion and metastasis
what is hypertrophy?
enlargement in individual cell size
what is hyperplasia?
increase in number of cells
what is metaplasia?
replacement of mature tissue types/change from one type to another
what is dysplasia?
abnormality indicating precursor change of malignancy
cell types not where they’re supposed to be
what is anaplasia?
failure to differentiate
how do malignant tumours behave?
- invasion
- metastasis
- angiogenesis
what is invasion?
- invades adjacent structures
- destroys normal tissue
what is metastasis?
spread to distant sites/forms new tumours in new areas
what can cause a tumour to undergo invasion?
➢ Increased motility [from solid tissue to a mesenchymal]
➢ Decreased adhesion [lose tissue component]
➢ Production of proteolytic enzymes [to lose the fixed components keeping them in place]
➢ Mechanical pressure [can also cause local invasion]
what are the adhesion molecules that attach cell to cell?
cadherins
what are the adhesion molecules that attach cell to extracellular matrix?
integrins
what would happen if a mutation of e-cadherins was to occur?
loss of cell-cell adhesion and contact inhibition
what would happen if changes in integrin expression was to occur?
lead to decreased cell-matrix adhesion (cell would be mobile)
In cancer epithelial cells gain mesenchymal properties, what does this mean?
they can become loosely connected, able to migrate
which enzyme degrades collagen type I, II, III?
interstitial collagenases
which enzyme degrades collagen type IV and gelatin?
gelatinases
which enzyme degrades collagen type IV and proteoglycans?
stomolysins
collagen type I is the main component of what?
skin
collagen type II is the main component of what?
hyaline and cartilage
collagen type III is the main component of what?
bone
collagen type IV is the main component of what?
basement membrane
what are Proteolytic Enzymes?
Matrix Metalloproteinases
degrade extracellular matrix (allows local invasion)
how can benign tumours cause damage?
mechanical pressure
- Pressure occludes vessels
- Pressure atrophy
[Even though not malignant, surrounding tissues can be destroyed due to
compression of feeding vessels causing atrophy]
in metastasis which is often the most damaging tumour - the primary or secondary site?
Secondary tumour burden is often greater than that of the primary site
list routes of metastasis
- lymphatic
- blood
- transcoelomic
- implantation
what is meant by the transcoelomic route of metastasis?
Across peritoneal, pleural, pericardial cavities or in CSF
what is meant by the implantation route of metastasis?
Spillage of tumour during biopsy/surgery [tumour can spread along the
needle tract]
what are the stages of metastasis?
➢ Detachment invasion ➢ Intravasation ➢ Survival against host defences ➢ Adherence extravasation ➢ Growth ➢ Angiogenesis
in the stages of metastasis, what is meant by intravasation?
[go into the blood stream]
in the stages of metastasis, what is meant by adherence extravasation?
[gain pathway outside the blood vessel into a new host tissue]
what route of metastasis do carcinomas usually take?
lymphatic spread first
what route of metastasis do sarcomas usually take?
blood spread first
where do bone mets often come from?
breast prostate lung kidney thyroid
which type of cancer commonly performs transcoelomic metastasis?
ovarian
brain and adrenal secondary sites are usually a result of which primary site?
lung
what are the two types of bone mets?
lytic (lung)
or
sclerotic (prostate)
what is the mechanical hypothesis?
idea that cancer metastasis is dictated by anatomy
e.g. lymphatic drainage. Liver mets in GI cancer
what is the seed and soil?
organ-preference patterns of tumor metastasis are the product of favorable interactions between metastatic tumor cells (the “seed”) and their organ microenvironment (the “soil”)
what is angiogenesis?
New vessel formation
- roles in development and healing
what factors promote angiogenesis?
VEGF
PDGF
TGFβ
what factors inhibit angiogenesis?
ECM proteins
Thrombospondin
Canstatin
Endostatin
why do we stage and grade cancer?
- determine prognosis (survival time, quality of life)
- decide how to treat tumour
- research
what is meant by the stage of a cancer?
the extent of
spread
Stage = How far along the arrow the tumour is
what is meant by the grade of a cancer?
how aggressive is the tumour?
Grade = How quickly the tumour progresses along the arrow
what system is used to stage tumours?
TNM system
● T = TUMOUR
● M = METASTASES
● N = NODES
with reference to TNM staging, what would you measure for T stage?
T = Size +/- extent of primary tumour
with reference to TNM staging, what would you measure for M stage?
M0 - no distant mets
M1 - distant mets.
with reference to TNM staging, what would M1 mean?
distant mets
with reference to TNM staging, what would M0 mean?
no distant mets
with reference to TNM staging, what would T4 mean?
tumour involves skin or chest wall
with reference to TNM staging, what would T3 mean?
tumour is >5cm in size
with reference to TNM staging, what would T2 mean?
tumour is 2-5cm in size
with reference to TNM staging, what would T1 mean?
tumour is < 2cm in size
with reference to TNM staging, what would Tis mean?
in situ disease (hasn’t spread yet)
with reference to TNM staging, what would you measure for N stage?
N0 - no nodes
N1 - Ipsilateral nodes
N2 - >node involvement
describe stage 0 breast cancer with reference to the TNM system?
Tis
treatment: surgery
describe stage I breast cancer with reference to the TNM system?
T1, N0, M0
treatment: surgery and RT
describe stage II breast cancer with reference to the TNM system?
T1-2, N1 or T3
treatment: surgery and chemo
describe stage III breast cancer with reference to the TNM system?
T(any)
N2 or T4
treatment: chemo
describe stage IV breast cancer with reference to the TNM system?
T(any)
N(any)
M1
treatment: chemo
what is the treatment for stage 0 breast cancer?
surgery only.
what is the treatment for stage I breast cancer?
surgery and RT
what is the treatment for stage II breast cancer?
surgery and chemo
what is the treatment for stage III and onwards breast cancer?
chemo.
with reference to dukes staging for colorectal cancer, what does A mean?
A = invades into, but not through bowel wall
A = >90% 5 year survival
with reference to dukes staging for colorectal cancer, what does B mean?
B = invades through the bowel wall but with no lymph node metastases
B = 70% 5 year survival
with reference to dukes staging for colorectal cancer, what does C mean?
C = Local lymph nodes involved
C = 30% 5 year survival
with reference to dukes staging for colorectal cancer, what does D mean?
D = Distant metastases
D = 5-10% 5 year survival
what factors is grading a tumour based on?
➢ Differentiation – how much does the tumour resemble tissue it originates from
➢ Nuclear pleomorphism and size
➢ Mitotic activity
➢ Necrosis [a sign of aggressive tumour i.e. tumour is outgrowing its own vascular supply]
NB: Grading performed by histopathologists - it is subjective
