Lecture 40 - Behaviour of tumours Flashcards
How many new cases of cancers occur every year in the UK?
350,000
True or false: Cancer causes more than 1 in 4 deaths in the UK
True
How do malignant tumours behave?
- Invasion
- Metastasis
- Angiogenesis
What is invasion of malignant tissue?
Invades adjacent normal tissue
Destroys normal tissue
What is metastasis of malignant tissue?
Spreads from site of origin to a distant site establishes a new tumour there
What is the name of the mechanisms used my cancerous cells allowing them to become more mobile and free moving?
epithelial-mesenchymal transition
what is require for a tumour to metastasise?
Invasion
Describe the typical arrangement of epithelial cells:
tightly connected, polarised and tethered to one another
Describe the typical arrangement of mesenchymal cells:
loosely connected (meaning they are able to migrate)
What are the two stages of the epithelial-mesenchymal transition?
1) reducing adhesion
2) producing proteolytic enzymes
3) Increased motility
4) Mechanical pressure
How does cancer spread using epithelial - mesenchymal transition?
In cancer, epithelial cells gain mesenchymal properties and can invade and migrate
Give an example of a cell-to-cell adhesion molecule:
cadherins
A mutation in E-cadherin in the tumour reduced cell-cell adhesion.
Give an example of a cell to matrix adhesion molecule:
integrin
Changes in integrin expression leads to decreased cell-matrix adhesion
What is the most important proteolytic enzyme in neoplastic invasion?
Matrix metalloproteinases
What cells secrete matrix metalloproteinases?
malignant neoplastic cells
Give three examples of matrix metalloproteinases:
1) interstitial collagenases
2) gelatinases
3) stromelysins
What proteins does interstitial collagenase break down?
type I, II and III collagen
What proteins does gelatinase break down?
type IV collagen and gelatine
What proteins does stromelysin break down?
type IV collagen and proteoglycans
Describe the balance between matrix metalloproteinases and tissue inhibitors of metalloproteinases in cancer?
the tissue favours extracellular matrix breakdown
What path do malignant neoplasms invade along?
the path of least resistance
Give two examples of ‘paths of least resistance’ used my malignant neoplasms when invading?
1) blood vessels
2) nerves
What is metastasis?
where a tumour spreads from the site of origin (primary) to a distant site to establish a tumour there (secondary)
True or false: the tumour mass of the secondary tumour exceeds that of the primary lesion
true
What two things are extremely resistance to neoplastic invasion?
1) Cartilage
2) Bone
Give three easily identifiable clinical presentations of metastasis:
1) palpable lymph nodes
2) ascites
3) bone lesions
What is the first step in the metastatic sequence?
detachment invasion
What is detatchement invasion?
where cells of a primary tumour break away
What is the name given to the process of malignant tumour cells entering blood vessels?
intravasation
Give an example of a method used by tumour cells to evade the host immune system when travelling in the blood:
tumour cells remove their MHC I expression to reduce detection
What is the name of the process whereby tumour cells anchor to the wall of the endothelium and exit blood vessels?
adherence extravasation
Give the four main routes of metastasis:
1) lymphatics
2) haematogenous
3) transcoelomic
4) implantation
Where do secondary tumours from when cancers spread through lymphatics?
lymph nodes
What is the most common route of metastasis used by carcinomas?
lymphatic route
What is the most common route of metastasis used by sarcomas?
haematogenous route
What organs are common sites of secondary tumours when cancers spread through the blood? (4)
1) liver
2) lungs
3) bone
4) brain
Where do bone metastases most frequently come from?
1) Lung
2) Breast
3) Kidney
4) Thyroid
5) Prostate
What is the transcoelomic route of metastasis?
spread across the peritoneum or pleural cavity leading to an effusion containing neoplastic cells
What is the implantation route of metastasis?
the spillage of tumour cells in surgery
Fill in the gap: tumours cannot grow more than _-_mm without a blood supply
2-3mm
What is angiogenesis?
Growth of blood vessels on existing vasculature
Normal part of growth and healing
What molecule do tumour cells express to promote the sprouting of new vessels?
vascular endothelial growth factor (VEGF)
What is meant by ‘stage’ in relation to cancer?
the extent of tumour spread/ how far along the tumour is (has it metastasised?)
What is meant by ‘grade’ in relation to cancer?
the extent of aggressiveness of a tumour/ how quickly it is progressing
What system is used to assess the stage of a cancer?
The TNM staging system
What does TNM stand for?
tumor-node-metastasis
What does the TNM scale assess?
the extent of tumour and nodal spread and metastasis
What staging system is used for colorectal cancer?
Dukes staging system
What is meant by the A-D scale used in Dukes staging system for colorectal cancer?
A- no invasion through the bowel wall
D- distant metastasis
What staging system is used for lymphomas?
Ann Arbor system
What is stage 1 Lymphoma?
Lymphoma in one group of lymph nodes
What is stage 2 Lymphoma?
Lymphoma in 2 or more groups of lymph nodes
What is stage 3 Lymphoma?
Lymphoma both sides of diaphragm
What is stage 4 Lymphoma?
Lymphoma in organ not part of lymphatics / lymphoma in bone marrow, liver or lung
What are the two grades of cancer?
low and high grade
What things do we consider when we are determine the grade of the cancer?
- How much do the cancer cells resemble the normal tissue = differentiation
- The variation in size and shape of the cancer cells = pleomorphism
- How many cells are actively dividing, can count mitotic figures = proliferation
How does well differentiated tumours present?
Cells closely resemble those of normal tissue = low grade
How does a poorly differentiated tumour differentiated?
Cells hardly resemble those of normal tissue = high grade
Does mitoses only indicated malignancy?
mitoses can be seen in normal tissue do not indicate malignancy
What type of mitotic figures are seen during malignancy?
Tripolar
Quadripolar
Multipolar spindles
