Cancer Genomics An introduction - Week 10

Question 1

Statistics

Answer 1

Cancer is the second leading cause of death in the world
Testicular cancer – 98% of patients survive 10 years or more
Pancreatic cancer – only 1% of patients survive 10 years or more

Question 2

What is Cancer

Answer 2

Uncontrollable cell division where the abnormally dividing cells eventually spread to or invade other tissues – metastasis which could lead to the death of a patient

Question 3

Cell division - mitosis

Answer 3

Cell reproduce by cell division (mitosis)

1 cell becomes 2, 2 cells become 4, 4 cells become 8 etc
• Mechanism for making new body cell and is distinct from meiosis (making egg and sperm cells – not covered in this module)
• The cell cycle is the whole series of changes the cell goes through from the time it is first formed until it divides into two daughter cells starting and ending with mitosis

Question 4

In normal healthy tissue the progression through cell division/ cell cycle is

Answer 4

tightly regulated and only occurs when needed stimulated by cell signalling pathways

Question 5

Cancer Terminology

Answer 5

Cancer or neoplasia (neo – new, plasia – tissue/cell) or malignant tumour

Question 6

Tumour

Answer 6

swelling or mass

Question 7

tumour in the context of cancer

Answer 7

referring to a mass of non structured new cells with no known purpose in the physiological function of the body

Question 8

Benign - differentiation

Answer 8

Well differentiated, structure similar to tissue of origin (more likely to retain some of the function of their cell of origin

Question 9

Benign - rate of growth

Answer 9

Slow growing and may halt or regress

Question 10

Benign - local invasion

Answer 10

Usually cohesive and well defined (capsular), does not invade or infiltrate into other tissues (relatively innocent)

Question 11

Benign - metastasis

Answer 11

Absent (do not spread to other sites in the body

Question 12

Malignant - differentiation

Answer 12

Poorly differentiated (or completely undifferentiated or anaplastic)

Question 13

Malignant - rate of growth

Answer 13

Erratic but can be fast (faster than benign)

Question 14

Malignant - local invasion

Answer 14

Locally invasive and infiltrates surrounding tissue (invade and destroy adjacent structures and spread/metastasise to different sites in the body)

Question 15

Malignant - metastasis

Answer 15

Frequent but more likely with large undifferentiated tumours

Question 16

• Benign tumours

Answer 16

In general have the suffix OMA attached to the name of the cell type the tumour originates
 Fibroma (fibrous tissue benign neoplasm)
 Adenoma (Epithelial benign neoplasm)

Question 17

Malignant tumours

Answer 17

Similar nomenclature as benign tumours (with additions)
 Fibrosarcoma
 Adenocarcinoma

Question 18

Liver =

Answer 18

Hepatic adenoma (benign) or hepatocellular carcinoma (malignant)

Question 19

Metastasis

Answer 19

(characteristic that differentiates benign and malignant tumours)
• Spread of a tumour to sites that are physically discontinuous from the primary tumour. Metastatic spread of a tumour decreases the possibility of a cure so understanding metastatic spread is critical especially when approximately 30% of newly diagnosed solid tumours present with metastases.

Question 20

Depending on how lymph and blood travel through the body Primary tumours often have a preferred site of metastasis

Answer 20

in addition to the lymph nodes i.e. tumours of bladder, breast, colon and ovary
From these examples you can see that bone, liver and lung are common sites of metastasis

Question 21

Three main pathways that a tumour can spread to distant sites

Answer 21

Seeding of body cavities and surfaces (can occur when a malignant tumour penetrates into an open field such as the peritoneal cavity in ovarian cancer, spread through

Lymphatic spread of cancer cells (spread through the lymphatic system is the most common pathway for the initial dissemination of carcinomas while tumours do not contain functional lymphatic vessels, it appears that the vessels at the edges of tumours are sufficient for lymphatic spread.)

Hematogenous spread (blood vessels) (tumours can also spread through nearby blood vessels either through veins (more common) and arteries (less common as arteries are thicker, more muscular and harder for tumour cells to penetrate)

Question 22

Metastasis are a multiple step process and involve

Answer 22

growing into or invading nearby tissue, moving through the walls of nearby lymph or blood vessels, travelling through the lymphatic/blood stream to other parts of the body. Stopping in small blood vessels at a distant location then managing to invade these blood vessels and moving into surrounding tissue, ultimately growing into a tiny tumour which develops blood vessels which will allow it to keep growing to a larger size.

Question 23

To undergo these metastatic step processes,

Answer 23

tumour cells have to acquire a number of different characteristics. Similarly normal cell to become a tumour cell initially the normal cell needs to acquire a number of different characteristics

Question 24

Collectively these characteristics are defined as the

Answer 24

“hallmarks of cancer” and were first defined by Hanahan and Weinberg in 2000

Question 25

To help inform treatment decisions and inform patients of their prognosis, cancers are examined to determine

Answer 25

stage and grade:

Question 26

grade

Answer 26

histological assessment of state of differentiation

Question 27

differentiation of low grade tumours

Answer 27

generally well differentiated

Question 28

differentiation of high grade tumours

Answer 28

poorly differentiated or completely undifferentiated

Question 29

Grade X

Answer 29

Grade isn’t known

Question 30

Grade 1

Answer 30

Well differentiated, low grade

Question 31

Grade 2

Answer 31

Moderately differentiated, intermediate grade

Question 32

Grade 3:

Answer 32

Poorly differentiated, high grade

Question 33

Grade 4:

Answer 33

Undifferentiated, high grade

Question 34

Grading used for most tumours except for some exceptions i.e.

Answer 34

o Gleason score for prostate cancer

o Nottingham score for prostate cancer

Question 35

Stage

Answer 35

looking at the size and spread of the tumour

Question 36

Solid tumours TNM system (most common system)

Answer 36

 T = Primary tumour (size, invasive depth and infiltration)
 N = Involvement of the lymph nodes (number of lymph nodes)
 M = Distant metastases (have distant metastases been observed)

Question 37

Each tumour type has its own and often complex staging system based on these principles but there are 2 main systems :

Answer 37

 Union of Internal Cancer Control (UICC)
• Aims to be more succinct, meets the needs of the worldwide community and used in the UK
 American Joint Committee on Cancer (AJCC)
• Aims to be comprehensive and meet the needs of US academics
 Both systems are very similar