Revision

Question 1

reversible change in which one adult cell type is replaced by another adult cell type

Answer 1

metaplasia

Question 2

examples of metaplasia

Answer 2

• Barret’s Oesophagus from squamous epithelium to columnar

- In the cervix from columnar to squamous epithelium

Question 3

abnormal pattern of growth with some morphological features of malignancy present

Answer 3

dysplasia

Question 4

what are the features of dysplasia?

Answer 4

• pre-invasive stage
• basement membrane still intact
• Loss of orientation
• Loss of uniformity
• Hyperchromatic and enlarged nuclei
• Mitotic figures in abundance but in abnormal places

these determine whether the dysplasia is high or low grade

Question 5

what are some common causes of dysplasia?

Answer 5

• HPV infection in the cervix
• Smoking in the bronchus
• Ulcerative colitis in the colon
• Pernicious anaemia in the stomach
• Acid reflux in the oesophagus –> Barrett’s

Question 6

A new abnormal proliferation of cells that are unresponsive to normal growth mechanisms

Answer 6

Neoplasia

Question 7

what is malignancy?

Answer 7

An abnormal autonomous proliferation of cells unresponsive to normal growth control mechanisms

Question 8

what is metastasis?

Answer 8

Discontinuous growing colony of tumour cells at a distance from the primary cancer site

Question 9

what types of draining are important to determine the metastasis risk?

Answer 9

lymph and vascular drainage

Question 10

benign epithelial tumour types

Answer 10

surface

glandular

Question 11

surface epithelium

Answer 11

papilloma

skin, bladder

Question 12

glandular epithelium

Answer 12

adenoma

stomach, thyroid, kidney, pancreas

Question 13

malignant epithelial tumour types

Answer 13

Squamous cell
Adenocarcinoma
Transitional Cell
Basal Cell

Question 14

where do sarcomas arises from

Answer 14

connective tissue types
(soft tissue/ mesenchymal tissue)

e.g.osteosarcoma, chondrosarcoma

Question 15

what is leukaemia?

Answer 15

Malignant tumour of bone marrow derived cells that circulate in the blood

Myeloid or lymphoid lineage

myeloid: RBCs, platelets, granulocytes
lymphoid: B and T lymphocytes, NK cells

Question 16

what is lymphoma?

Answer 16

Malignant tumour of lymphocytes usually within the lymph nodes (otherwise just the lymphatic system)

Question 17

what is a teratoma?

Answer 17

Tumour derived from germ cells

• from 1 to all 3 layers (ectoderm, mesoderm, endoderm)
• found ectopically

Question 18

how do male gonadal teratomas differ to female gonadal teratomas differ?

Answer 18

Male gonadal teratomas are malignant

Female gonadal teratomas often benign

Question 19

what is a hamartoma?

Answer 19

Localised overgrowth of cells/tissue native to the organ that are disorganised but are histologically normal

key: disorganised structure , normal histology

Question 20

features of benign tumours

Answer 20

• encapsulated
• well differentiated
• slow growing
• normal mitoses
• do not invade
• do not metastasise

Question 21

feature of malignant tumours

Answer 21

• no capsule
• poorly differentiated often
• fast growing
• abnormal mitoses
• invades surrounding tissue
• metastasises

Question 22

what features of a tumour can help grade the tumour i.e. degree of differentiation?

Answer 22

• a large nucleus
• irregular shape and size
• nucleoli prominent
• scarce cytoplasm
• cytoplasm intensely coloured or pale
• lack of normal function

Question 23

what features of a tumour help you stage the tumour i.e. the spread of the tumour?

Answer 23

this is more important for diagnosis
indicated whether the lymph nodes are involved –> if so, poorer prognosis

TNM:

• tumour size
• node involvement
• metastasis

Question 24

which staging system is used for colorectal cancer?

Answer 24

Duke’s

based on invasion the basement membrane

Question 25

what is a proto-oncogene?

Answer 25

A piece of genetic material that codes for normal and essential proteins needed for controlled cell growth, division and differentiation

Question 26

examples of proto-oncogenes

Answer 26

- Growth Factor - Growth factor receptor - signalling proteins - intracellular receptors - cell cycle regulatory proteins - cell death regulators

Question 27

what is an oncogene?

Answer 27

A piece of genetic material that codes proteins promoting uncontrolled cellular proliferation

Question 28

how are oncogenes expressed in cancer?

Answer 28

- abnormally - excessively - hyperactively

Question 29

examples of oncogenes with the potential to cause cancer

Answer 29

- Ras protein - c-Myc - Raf protein

Question 30

how are oncogenes activated (from proto-oncogene) ?

Answer 30

- mutation in coding sequence - gene amplification (overproduction) - chromosomal translocation e.g. Philly (bcr-abl--> CML) - insertional mutagenesis (e.g. viral integration)

Question 31

what will a mutant Ras protein do?

Answer 31

Does not allow the GAP proteins to function and dephosphorylate the GTP to GDP therefore Ras DOES NOT DEACTIVATE and will be constantly active

Question 32

what is the effect of a constantly active Ras protein?

Answer 32

- Abnormal growth - Abnormal proliferation - Abnormal differentiation

Question 33

Knudson’s two-hit hypothesis

Answer 33

two mutations are required for the TSG to lose control of its regulatory function one mutation may be inherited whilst the other is acquired

Question 34

example of TSG function

Answer 34

- regulate cell proliferation - maintain cellular integrity - regulate cellular growth - regulate the cell cycle - nuclear TFs - DNA repair proteins - cell adhesion molecules - cell death regulators

Question 35

example of TSG

Answer 35

- p53 | - APC (in Familial Adenomatous Polyposis)

Question 36

what is unique about p53 as a TSG

Answer 36

only 1 copy is needed to be mutated/lost for there to be functional dysregulation.

Question 37

what effect does an Adenomatous Polyposis Coli gene mutation have?

Answer 37

uncontrolled growth--> polyps each polyp increases the chance of cancer

Question 38

what is beta catenin?

Answer 38

involved in regulation and coordination of cell–cell adhesion and gene transcription. normally bound to cadherin in adheren junctions

Question 39

what pathway is APC involved in?

Answer 39

``` Wnt pathway (part of a destruction complex) --> controlling beta-catenin degradation ```

Question 40

what will happen when beta catenin is not being degraded by APC?

Answer 40

LEF-1 will create a transcription complex with beta catenin to alter gene expression and proliferation

Question 41

how is beta catenin expressed in Familial Adenomatous Polyposis?

Answer 41

high levels of beta catenin due to ineffective APC mutation (no degradation) therefore increased transcription and proliferation via LEF-1 pathway

Question 42

when does colon cancer develop in normal epithelium?

Answer 42

when there is an APC mutation

Question 43

when does colon cancer develop in hyperproliferative epithelium?

Answer 43

when there is a k-ras mutation

Question 44

when does colon cancer develop when there is an adenoma?

Answer 44

when there is a p53 mutation

Question 45

what are the features of oncogenes?

Answer 45

- active in tumour - translocations/point mutations - not often inherited - dominant: one mutation enough - e.g. leukaemia, lymphomas

Question 46

what are the features of TSGs?

Answer 46

- inactive in tumour - deletions/mutation - inheritable mutations - recessive: 2 hit - solid tumours especially

Question 47

responses by p53

Answer 47

- cell arrest - DNA repair - apoptosis - senescence

Question 48

what are the main two tests for prostate cancer?

Answer 48

1) Direct Rectal Exam (but does not detect microscopic tumour) 2) Prostate Specific Antigen