Behaviour of tumours Flashcards
What are the different types of tumour behaviour?
Invasion, metastasis and angiogenesis
What is invasion?
- Invades adjacent normal tissue
- Destroys normal tissue
What is metastasis?
Spreads from site of origin to distant sites and forms new tumours in these new areas
What are the features of invasion?
- Increased motility
- Decreased adhesion
- Production of proteolytic enzymes
- Mechanical pressure
What are cadherins and what is their role in cancer?
Cell to cell adhesion molecules.
Mutation of E-cadherin leads to loss of cell-cell adhesion and contact inhibition
What are integrins and what is their role in cancer?
Cell to matrix adhesion molecules.
Changes in integrin expression lead to decreased cell-matrix adhesion
What is the difference between normal epithelial and mesenchymal cells.
- Epithelial cells are tightly connected, polarised and tethered
- Mesenchymal cells loosely connected, able to migrate
What is epithelial-mesenchymal transition?
In cancer epithelial cells gain mesenchymal properties and can invade and migrate.
Which proteolytic enzymes are active in cancer?
Matrix Metalloproteinases - degrade extracellular matrix.
Interstitial collagenases, gelatinases, stomolysins
What are the potential routes of metastasis?
Lymphatic
- Distant or local lymph nodes
Blood
- Liver, lungs, bone, brain etc
Transcoelomic
- Across peritoneal, pleural, pericardial cavities or in CSF
Implantation
- Spillage of tumour during biopsy/surgery
What are the stages of metastasis?
- Intravasation
- Detachment/invasion
- Survival against host defences
- Adherence and extravasation
- Angiogenesis
- Growth
By which route do carcinomas typically spread?
Lymphatic (first)
By which route do sarcomas typically spread?
Blood (first)
Which cancers are most commonly associated with bone mets?
Breast Prostate Lung Kidney Thyroid
Which cancer is most commonly associated with transcoelomic spread?
Ovarian
Which cancer is most commonly associated with brain and adrenal mets?
Lung
What is the mechanical hypothesis?
Dictated by anatomy eg, lymphatic drainage. Liver mets in GI cancer
What else is important in metastasis?
- Tissue environment is important – influences organ selectivity for metastases
- Metastatic cells can remain dormant for years
Why is angiogenesis essential?
If metastases are to grow larger than 1-2mm
Which growth factors are promoters of angiogenesis?
VEGF
PDGF
TGFβ
What factors are inhibitors of angiogenesis?
ECM proteins
Thrombospondin
Canstatin
Endostatin
What is stage?
How advanced is the tumour? Has the cancer spread and if so what is the extent of spread.
What is grade?
How aggressive is the tumour? How different does it look from tissue of origin.
How are tumours staged?
Tumours are staged using TMN
T = Size +/- extent of primary tumour M = Presence and extent of distant metastases N = Presence and number of lymph node metastases
Can be combined to give an overall stage for the tumour (I-IV)
Each organ has an individual TMN system
Stage can be clinical, pathological or radiological
What is the Dukes staging for colorectal cancer?
A = invades into, but not through bowel wall B = invades through the bowel wall but with no lymph node metastases C = Local lymph nodes involved D = Distant metastases
How is grading determined?
- Differentiation – how much does the tumour resemble tissue it originates from
- Nuclear pleomorphism and size
- Mitotic activity
- Necrosis
