Behaviour of tumours

Question 1

What are the different types of tumour behaviour?

Answer 1

Invasion, metastasis and angiogenesis

Question 2

What is invasion?

Answer 2

• Invades adjacent normal tissue

- Destroys normal tissue

Question 3

What is metastasis?

Answer 3

Spreads from site of origin to distant sites and forms new tumours in these new areas

Question 4

What are the features of invasion?

Answer 4

• Increased motility
• Decreased adhesion
• Production of proteolytic enzymes
• Mechanical pressure

Question 5

What are cadherins and what is their role in cancer?

Answer 5

Cell to cell adhesion molecules.

Mutation of E-cadherin leads to loss of cell-cell adhesion and contact inhibition

Question 6

What are integrins and what is their role in cancer?

Answer 6

Cell to matrix adhesion molecules.

Changes in integrin expression lead to decreased cell-matrix adhesion

Question 7

What is the difference between normal epithelial and mesenchymal cells.

Answer 7

• Epithelial cells are tightly connected, polarised and tethered
• Mesenchymal cells loosely connected, able to migrate

Question 8

What is epithelial-mesenchymal transition?

Answer 8

In cancer epithelial cells gain mesenchymal properties and can invade and migrate.

Question 9

Which proteolytic enzymes are active in cancer?

Answer 9

Matrix Metalloproteinases - degrade extracellular matrix.

Interstitial collagenases, gelatinases, stomolysins

Question 10

What are the potential routes of metastasis?

Answer 10

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

Question 11

What are the stages of metastasis?

Answer 11

1. Intravasation
2. Detachment/invasion
3. Survival against host defences
4. Adherence and extravasation
5. Angiogenesis
6. Growth

Question 12

By which route do carcinomas typically spread?

Answer 12

Lymphatic (first)

Question 13

By which route do sarcomas typically spread?

Answer 13

Blood (first)

Question 14

Which cancers are most commonly associated with bone mets?

Answer 14

Breast
Prostate
Lung
Kidney
Thyroid

Question 15

Which cancer is most commonly associated with transcoelomic spread?

Answer 15

Ovarian

Question 16

Which cancer is most commonly associated with brain and adrenal mets?

Answer 16

Lung

Question 17

What is the mechanical hypothesis?

Answer 17

Dictated by anatomy eg, lymphatic drainage. Liver mets in GI cancer

Question 18

What else is important in metastasis?

Answer 18

• Tissue environment is important – influences organ selectivity for metastases
• Metastatic cells can remain dormant for years

Question 19

Why is angiogenesis essential?

Answer 19

If metastases are to grow larger than 1-2mm

Question 20

Which growth factors are promoters of angiogenesis?

Answer 20

VEGF
PDGF
TGFβ

Question 21

What factors are inhibitors of angiogenesis?

Answer 21

ECM proteins
Thrombospondin
Canstatin
Endostatin

Question 22

What is stage?

Answer 22

How advanced is the tumour? Has the cancer spread and if so what is the extent of spread.

Question 23

What is grade?

Answer 23

How aggressive is the tumour? How different does it look from tissue of origin.

Question 24

How are tumours staged?

Answer 24

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

Question 25

What is the Dukes staging for colorectal cancer?

Answer 25

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

Question 26

How is grading determined?

Answer 26

• Differentiation – how much does the tumour resemble tissue it originates from
• Nuclear pleomorphism and size
• Mitotic activity
• Necrosis