T5: Behaviour of Tumours Flashcards
How do malignant epithelial cells cause systemic disease?
- Increased motility
- Decreased adhesion
- Production of proteolytic enzymes
- Mechanical pressure
What is the most important proteolytic enzyme in neoplastic invasion?
Matrix metalloproteinases
What are the clinical effects of invasion?
Uncontrolled proliferation and invasion leading to a mass.
- The formation of a mass can occlude vessels and put pressure on tissues leading to clinical effects.
Malignant neoplasms invade along the “path of least resistance” - this is commonly blood vessels or nerve as cartilage and bone are extremely resistant to neoplastic invasion.
What is the sequence of events that lead to metastases?
Metastasis occurs by invasion, intravasation and survival against host cells (usually due to reduced expression to hide form the immune system). They then bind and adhere to the blood vessel at the site. They then have to proliferate in a new environment, in order to do this they require angiogenesis. Angiogenesis is required for a a tumour to grow more than 2cm.
- Detachment Invasion
- Intravasation
- Survival against host defences
- Adherence Extravasation
- Growth
- Angiogenesis
What is the most common route of metastasis for carcinomas?
Lymphatics
What is the most common route of metastasis for sarcomas?
Haematogenous - Organs most involved include the liver, lungs, bone and brain.
Where do bone metastases frequently come from?
Lung, Prostate, Breast, Kidney and thyroid
Other than lymphatics and haematogenous routes, what are other routes of metastases?
- Transcoelomic - spread via the perineum. This will lead rot an effusion contains neoplastic cells and so they may present with ascites e.g. ovarian cancer
- Implantations - such as spillage of tumour cells in surgery
How do tumour cells promote angiogenesis?
Tumours cells express vascular endothelial growth factor (VEGF) to promote new vessels sprouting and angiogenesis.
What does tumour staging tell us?
The extent at which the tumour has spread
What does tumour grading tell us?
How aggressive the tumour is.
Based on:
- How quick does it grow - How different does the tumour cells look form the tissue of origin
How do we use TNM staging?
This is the general staging system:
T- extent of tumour spread
T0: No evidence of primary tumour
T1-T4: Increasing size/invasion of tumour
N - Extent of nodal spread N0: No evidence of regional nodal spread N1-N3: Increasing involvement of nodes M - presence or absence of distant metastases M0: No distant metastases M1: distant metastases present
What staging system is also used in colorectal cancer?
Dukes Staging System - From A-D
A - Invades into but not through the bowel wall
B- Invades through the muscle layer of the bowel layer but there is no LN metastases
C - Local lymph nodes involved
D- Distant Metastases
It is often used alongside TNM
What staging system is also used in lymphoma?
Ann Arbour - Stage I - IV.
Stage I - Lymphoma is one group of lymph nodes
Stage II - Lymphoma in 2 or more groups of lymph nodes
Stage III - Lymphoma both sides of the diaphragm
Stage IV - Lymphoma in organ not part of lymphatics/lymphoma in the bone marrow, liver to lung
Further classification depending on presence or absence of systemic symptoms such as fever and weight loss. A - symptoms are absent; B - symptoms are present.
What do we consider when grading a tumour?
- Generally split into low and high - sometimes medium
- Determined by pathologist - it is subjective
Look at:
a. How much of the cancer cells resemble the normal tissue - differentiation
b. The variation in size and shape of the cancer cells - pleomorphism
c. How many cells are actively dividing, can count mitotic figure - proliferation
Graded into well differentiated (closely resampled the cells of the normal tissue and are low grade), moderately differentiated and poorly differentiated (hardly resemble those of normal tissue and so are high grade).
What is pleomorphism?
The cancer is called pleomorphic because the cells grow in multiple shapes and sizes.
How does grade correlate with outcome?
As a grade gets worse, the survival gets worse.
What is epithelial-mesenchymal transition?
Normally epithelial cells are tightly connected, polarised and tethered to each other. In contrast mesenchymal cells loosely connected and are able to migrate. In cancer epithelial cells gain mesenchymal properties and can invade and migrate - this is termed the epithelial-mesenchymal transition.
What are the 3 types of metalloproteinases?
Interstitial Collagenases - digests collagen I, II and III
Gelatinases - degrades collagen type IV and gelatine
Stromelysins - degrades collagen type IV and proteoglycans
What is the role of cadherins and integreins in carcinogenesis?
Epithelial cells are joined to each other between cell-to-cell molecules e.g. cadherins. A mutation in E-cadherin in the tumour leads to reduced cell-to-cell adhesion. There are also adhesins that adhere the cell to the matrix e.g. integrin. Changes in integrin expression leads to decreased cell-matrix adhesion.
How is proliferation different in normal cells compared to tumour cells?
In particular mitoses which are an indication of proliferation. Generally high grade tumours have lost of mitoses. Mitoses can be seen in normal tissue and so in itself do not indicate malignancy. Atypical, bizarre mitotic figures however are seen in malignancy. These include include:
- Tripolar
- Quadripolar
Multipolar spindles
What staging system is used in prostate cancer?
Gleason
