cancer

Question 1

Neoplasm / neoplasia / ‘tumour’?

Answer 1

Abnormal and excessive growth that is uncoordinated with that of the normal
surrounding tissue

Question 2

Benign vs malignant

Answer 2

Does not spread vs has the potential to metastasize
○ this can sometimes be defined based on the anatomical site and is linked to ‘stage’

Question 3

Adenoma vs adenocarcinoma

Answer 3

Benign tumors of epithelial cells vs malignant tumors of epithelial cells

Question 4

Metaplasia

Answer 4

○ Replacement of one type of mature differentiated cell with another

Question 4

Anaplasia

Answer 4

Reduced differentiation

Question 4

Dysplasia

Answer 4

Abnormal cell growth
○ Often associated with the microscopic appearance of variability between cells,
reduced cellular differentiation and maturation
○ Cells no longer have an uncontrolled structure/function

Question 5

Tumour evolution

Answer 5

Mutations and epimutations accumulate in the somatic cells of tumour
○ These changes are retained by tumour cells if they provide a competitive advantage
in terms of survival, proliferation, migration, resistance to immune response or
treatment etc
○ Selective pressure on tumours changes through the course of the tumour eg start of
tumour is very different to when patient receives chemotherapy

Question 5

Metastasis

Answer 5

The spread of tumour cells to distant sites such as lymph nodes or distant organs,
either via lymphatics or blood vessels
○ The ability to metastasize defines a malignant tumour
○ For some tumours, it is difficult to metastasise if they are not close to blood vessels
or lymphatics

Question 6

Proliferation

Answer 6

Division of cells, controlled by signalling pathways which often become uncontrolled
in cancer

Question 7

Tumour heterogeneity

Answer 7

Genetic, epigenetic and gene expression differences between distinct regions of a
tumour, which may possibly result from tumour evolution
○ Different regions have different ways to compete

Question 8

Invasion

Answer 8

Local spread of a tumour - can destroy tissue
○ Local invasion of a benign tumour can be dangerous by damaging adjacent
structures, even though that tumour does not metastasize

Question 9

analplasia vs dysplasa

Answer 9

Anaplasia is reduced differentiation, while dysplasia is abnormal differentiation or cell growth. The
specific microscopic appearance of dysplasia includes pleomorphism (variation in size & shape
between cells), hyperchromatic nuclei (stain very densely), increased nucleus/cytoplasm ratio
(large nuclei), and loss of tissue architecture. Both anaplasia and dysplasia represent the failure of
normal signalling pathways in cells due to genetic or epigenetic changes (loss of cellular ‘social
responsibility’). Both benign and malignant tumours can have degrees of anaplasia and dysplasia,
however these appearances are much more marked and common in malignant tumours.
Sometimes benign tumours may have small regions of dysplasia/anaplasia, and this could be a
precursor to invasion and metastasis.

Question 10

Stage

Answer 10

How far has a cancer developed and spread, in
terms of primary tumour growth and invasion,
and in terms of distant metastasis
○ TNM stage - tumour, node, metastasis
○ TIS tumour has not yet invaded through the
muscularis mucosae into the submucosa -
cannot access lymph vessels and blood vessels

Question 10

Grade

Answer 10

How aggressive and unlike the originating cell type the cancer looks under the
microscope
○ Especially in terms of proliferation (aggressive cell growth) and anaplasia (losing
differentiation)
○ Indicates molecular signalling pathways are disrupted
○ Can give an estimate for the prognosis
○ High grade tumour looks aggressive = poor
prognosis

Question 11

describe cancer progression

Answer 11

Question 11

when does cancer occur?

Answer 11

As the tumour grows, hormones are released and these are ‘signals’. Problems are caused by the
tumour growing in inappropriate places, and these are ‘blockages’. These are what lead to the
symptoms which will then allow us to detect the cancer.
Cancer can occur when:
● There are too many cells
○ Dysregulated cell cycle or uncontrolled proliferation
○ Response to proliferative signals
○ Ignoring anti-proliferative signals
○ Avoiding cell death
○ Evading the immune system
● Cells doing the wrong job at the wrong time
○ Dedifferentiation - losing normal function
● Cells in the wrong place in the body
○ Due to angiogenesis, invasion, metastasis - cells in search of nutrients and oxygen
and to evade the immune system

Question 12

how does smoking increase your chance of cancer

Answer 12

Tobacco smoke (chemical exposure)
Smoking is associated with a number of cancers - lung, stomach, pancreas, bowel, ovary etc due
to the number of carcinogens in the tobacco smoke. Chemicals in the cigarette smoke (e.g.
nicotine derivative nitrosaminoketone (NNK)) cause DNA adducts - direct mutations which the
body tries to repair but cannot. This chemical initiates G-T and G-A transitions across the DNA and at some point these mutations will hit a gene which is important for regulating cell growth. This
chemical also promotes via cell signalling, as it stimulates acetylcholine receptors (nAChRs).
These receptors are present on many cells,
and it leads to the initiation of angiogenesis
by endothelial cells, causes addiction, and
lung epithelial cells increase proliferation,
invasion and survival.

Question 12

what are the hallmarks of cancer?

Answer 12

These hallmarks that are present in a cancer cell
which allow it to proliferate,
evade the immune system
etc. Cancer is not just one
disease, it is multiple
diseases. Understanding the
journey of a particular
patient’s cancer will enable
the best treatment to be
chosen.

Question 13

describe tumour supressor genes vs protooncogenes

Question 14

describe onocgenes

Answer 14

Question 15

describe tumour supressor genes

Answer 15

Question 16

what are some indicators of famillal cancer

Answer 16

Question 17

describe the two hit hypothesis

Answer 17

For hereditary syndromes involving tumour suppressor genes, this is thought to be the mechanism. An inherited germline mutation inactivates one allele with the second acquired mutation resulting in the loss of activity of the second allele, and thus leading to the loss of activity of the tumour suppressor gene.

This theory was initially proposed for retinoblastoma an embryonic tumour of eye retinal cells in children. The familial form was an inherited mutation of 1 RB allele followed by somatic mutation of the other allele.The sporadic form was rare and usually unilateral, and
required somatic mutations of both RB alleles in thesame cell.

Question 18

describe famillial breast and ovarian cancer

Answer 18

Question 19

pplease read the breast clinical scenario