Carcinogenesis

Question 1

Hallmarks of cancer

Answer 1

self-sufficiency in growth signals
insensitivity to growth-inhibitory signals
evasion of apoptosis
immortality (limitless replicative potential)
sustained angiogenesis
altered cell metabolism
evasion of immune surveillance 
invasion + metastasis

Question 2

Dysplasia

Answer 2

disordered cell growth

Question 3

Neoplasia

Answer 3

new growth (unregulated, clonal + irreversible)
tumour/neoplasm = lesion resulting from autonomous abnormal growth of cells that persists in absence of initiating stimulus
any cell type can undergo neoplastic transformations to form neoplasm
benign or malignant

Question 4

Benign tumours features

Answer 4

remain localised
slow-growing
closely resemble tissue from which they arise
often circumscribed or encapsulated

Question 5

Malignant tumours features

Answer 5

invade surrounding tissues + may metastasise
often rapidly-growing
vary in resemblance to tissue of origin
usually have irregular margin

Question 6

What is a carcinoma in situ?

Answer 6

epithelial neoplasm showing all cellular features of malignancy but not yet invaded epithelial basement membrane, separated from potential metastasis routes (blood vessels + lymphatics)

Question 7

Benign cells features

Answer 7

low nuclear to cytoplasmic ratio
all nuclei similar size + not hyperchromatic
vesicular, evenly distributed chromatin
smooth nuclear membranes

Question 8

Malignant cells features

Answer 8

increased nuclear to cytoplasmic ratio
nuclear pleomorphism + hyperchromasia
irregular chromatin distribution within nucleus +/- prominent nucleoli
irregular nuclear membranes

Question 9

Carcinogenesis molecular sequence

Answer 9

molecular change happens in a gene which normally controls cell growth, cell survival or cell senescence
genetic changes overcome normal repair mechanisms and are transmitted to daughter cells
natural selection favours survival of the most aggressive clones
mutations and epigenetic alterations give cancer cells a set of properties called cancer hallmarks

Question 10

How are tumours classified?

Answer 10

histogenetic classification

• classified by specific cell or tissue of origin of tumour
• epithelial cells, connective tissue/mesenchymal cells, lymphocytes, haematopoietic cells

Question 11

Epithelial cell tumour name

Answer 11

malignant = carcinoma

Question 12

Squamous cell carcinoma features?

Answer 12

forms sheets

produces keratin

Question 13

Adenocarcinoma features?

Answer 13

forms glands

have mucin in cytoplasm

Question 14

What is connective/mesenchymal tissue?

Answer 14

muscles
nerves
tendons
blood vessels
adipose tissue
fibrous tissue

Question 15

Tumours of adipose tissue names?

Answer 15

benign = lipoma
malignant = liposarcoma

Question 16

Tumours of blood vessels names?

Answer 16

benign = haemangioma
malignant = angiosarcoma

Question 17

Tumours of skeletal muscle names?

Answer 17

benign = rhabdomyoma
malignant = rhabdomyosarcoma

Question 18

Tumours of smooth muscle names?

Answer 18

benign = leiomyoma
malignant = leiomyosarcoma

Question 19

Tumours of schwann cells names?

Answer 19

benign = schwannoma
malignant = MPNST (malignant peripheral nerve sheet tumour)

Question 20

Tumours of fibroblasts names?

Answer 20

benign = fibroma
malignant = fibrosarcoma

Question 21

lipoma vs liposarcoma

Answer 21

lipoma = uniform adipocytes
liposarcoma = large, atypical nuclei + clear cytoplasm (indicates presence of fat)

Question 22

leiomyoma vs leiomyosarcoma

Answer 22

leiomyoma = circumscribed (+covered by bowel mucosa)
leiomyosarcoma = pleomorphic atypical cigar-shaped nuclei

Question 23

Tumours of lymphocytes/haematopoietic cells names?

Answer 23

malignant tumour of lymphocytes (in lymph nodes) = lymphoma
malignant lymphocytes in bone marrow/peripheral blood = leukaemia
malignant tumour of haematopoietic cells = also a leukaemia

Question 24

Lymphoma features?

Answer 24

sinuses of lymph node no longer visible (filled with malignant lymphocytes), take over lymph node

Question 25

What is a tumour grade?

Answer 25

how closely a tumour resembles tissue from which it arises (differentiation)
indicates how aggressive a tumour is likely to be
grade 1 = well differentiated = closely resemble parent tissue
grade 3 = poorly differentiated = may not be very similar and may only be identified by reading antigenic expression profile using antibodies which target tissue-specific antigens = immunohistochemistry

Question 26

What is invasion?

Answer 26

malignant tumours can invade basement membrane + metastasise
(eg. in epithelial tumours, acquisition of motile + migratory properties required - normally associated with cells of mesenchymal lineage - change = epithelial-mesenchymal transition)

Question 27

What are the 3 main changes that occur when a cell becomes tumourigenic?

Answer 27

Immortalisation = property of indefinite growth
Cell fails to follow normal growth restraints = becomes independent of growth factors
Invasion = ability to invade normal tissue and metastasise

Question 28

Describe 3 heritable (cell-cell) changes in carcinogenesis:

Answer 28

• dominant driver mutations in oncogenes
• recessive driver mutations in tumour suppressor genes
• epigenetic changes (gene not altered in DNA sequence)

Question 29

What is a driver mutation?

Answer 29

alteration that gives cancer cell a fundamental growth advantage for its neoplastic transformation

Question 30

What is a passenger mutation?

Answer 30

no effect on the fitness of a clone but may be associated with a clonal expansion because it occurs in the same genome with a driver mutation

Question 31

Describe oncogenes

Answer 31

when a mutation occurs in a proto-oncogene, it can become an oncogene
oncogenes = drive uncontrolled cell growth
oncogene products involved in pathways that regulate growth
mutations dominant at cellular level = only one mutation on one allele can change cell phenotype
protein expressed by mutated oncogene usually has lack of regulation or increased activity

Question 32

Describe tumour suppressor genes

Answer 32

mutations of TSGs lead to loss of good function
normal role of proteins of TSGs = restain uncontrolled cell division (eg. trigger apoptosis)
normally loss of function in both alleles needed to have an effect (recessive)
sometimes associated with rare, familial cancers (germline mutation/deletion of one allele + inactivation/deletion of other eg. TP53 + Retinoblastoma)

Question 33

Cancer risk factors

Answer 33

germline/inherited mutations
carcinogens
age
obesity
lifestyle factors (smoking, alcohol)

Question 34

What is a carcinogen?

Answer 34

agents that increase frequency at which cells acquire cancer phenotype
chemicals, infectious agents or forms of radiation
2 classes:
- initiators = predispose cells to develop tumours
- promoters = stimulate tumour development