Revision Flashcards
reversible change in which one adult cell type is replaced by another adult cell type
metaplasia
examples of metaplasia
- Barret’s Oesophagus from squamous epithelium to columnar
- In the cervix from columnar to squamous epithelium
abnormal pattern of growth with some morphological features of malignancy present
dysplasia
what are the features of dysplasia?
- 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
what are some common causes of dysplasia?
- 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
A new abnormal proliferation of cells that are unresponsive to normal growth mechanisms
Neoplasia
what is malignancy?
An abnormal autonomous proliferation of cells unresponsive to normal growth control mechanisms
what is metastasis?
Discontinuous growing colony of tumour cells at a distance from the primary cancer site
what types of draining are important to determine the metastasis risk?
lymph and vascular drainage
benign epithelial tumour types
surface
glandular
surface epithelium
papilloma
skin, bladder
glandular epithelium
adenoma
stomach, thyroid, kidney, pancreas
malignant epithelial tumour types
Squamous cell
Adenocarcinoma
Transitional Cell
Basal Cell
where do sarcomas arises from
connective tissue types
(soft tissue/ mesenchymal tissue)
e.g.osteosarcoma, chondrosarcoma
what is leukaemia?
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
what is lymphoma?
Malignant tumour of lymphocytes usually within the lymph nodes (otherwise just the lymphatic system)
what is a teratoma?
Tumour derived from germ cells
- from 1 to all 3 layers (ectoderm, mesoderm, endoderm)
- found ectopically
how do male gonadal teratomas differ to female gonadal teratomas differ?
Male gonadal teratomas are malignant
Female gonadal teratomas often benign
what is a hamartoma?
Localised overgrowth of cells/tissue native to the organ that are disorganised but are histologically normal
key: disorganised structure , normal histology
features of benign tumours
- encapsulated
- well differentiated
- slow growing
- normal mitoses
- do not invade
- do not metastasise
feature of malignant tumours
- no capsule
- poorly differentiated often
- fast growing
- abnormal mitoses
- invades surrounding tissue
- metastasises
what features of a tumour can help grade the tumour i.e. degree of differentiation?
- a large nucleus
- irregular shape and size
- nucleoli prominent
- scarce cytoplasm
- cytoplasm intensely coloured or pale
- lack of normal function
what features of a tumour help you stage the tumour i.e. the spread of the tumour?
this is more important for diagnosis
indicated whether the lymph nodes are involved –> if so, poorer prognosis
TNM:
- tumour size
- node involvement
- metastasis
which staging system is used for colorectal cancer?
Duke’s
based on invasion the basement membrane
what is a proto-oncogene?
A piece of genetic material that codes for normal and essential proteins needed for controlled cell growth, division and differentiation
examples of proto-oncogenes
- Growth Factor
- Growth factor receptor
- signalling proteins
- intracellular receptors
- cell cycle regulatory proteins
- cell death regulators
what is an oncogene?
A piece of genetic material that codes proteins promoting uncontrolled cellular proliferation
how are oncogenes expressed in cancer?
- abnormally
- excessively
- hyperactively
examples of oncogenes with the potential to cause cancer
- Ras protein
- c-Myc
- Raf protein
how are oncogenes activated (from proto-oncogene) ?
- mutation in coding sequence
- gene amplification (overproduction)
- chromosomal translocation e.g. Philly (bcr-abl–> CML)
- insertional mutagenesis (e.g. viral integration)
what will a mutant Ras protein do?
Does not allow the GAP proteins to function and dephosphorylate the GTP to GDP
therefore Ras DOES NOT DEACTIVATE
and will be constantly active
what is the effect of a constantly active Ras protein?
- Abnormal growth
- Abnormal proliferation
- Abnormal differentiation
Knudson’s two-hit hypothesis
two mutations are required for the TSG to lose control of its regulatory function
one mutation may be inherited whilst the other is acquired
example of TSG function
- regulate cell proliferation
- maintain cellular integrity
- regulate cellular growth
- regulate the cell cycle
- nuclear TFs
- DNA repair proteins
- cell adhesion molecules
- cell death regulators
example of TSG
- p53
- APC (in Familial Adenomatous Polyposis)
what is unique about p53 as a TSG
only 1 copy is needed to be mutated/lost for there to be functional dysregulation.
what effect does an Adenomatous Polyposis Coli gene mutation have?
uncontrolled growth–> polyps
each polyp increases the chance of cancer
what is beta catenin?
involved in regulation and coordination of cell–cell adhesion and gene transcription.
normally bound to cadherin in adheren junctions
what pathway is APC involved in?
Wnt pathway (part of a destruction complex) --> controlling beta-catenin degradation
what will happen when beta catenin is not being degraded by APC?
LEF-1 will create a transcription complex with beta catenin to alter gene expression and proliferation
how is beta catenin expressed in Familial Adenomatous Polyposis?
high levels of beta catenin due to ineffective APC mutation (no degradation)
therefore increased transcription and proliferation via LEF-1 pathway
when does colon cancer develop in normal epithelium?
when there is an APC mutation
when does colon cancer develop in hyperproliferative epithelium?
when there is a k-ras mutation
when does colon cancer develop when there is an adenoma?
when there is a p53 mutation
what are the features of oncogenes?
- active in tumour
- translocations/point mutations
- not often inherited
- dominant: one mutation enough
- e.g. leukaemia, lymphomas
what are the features of TSGs?
- inactive in tumour
- deletions/mutation
- inheritable mutations
- recessive: 2 hit
- solid tumours especially
responses by p53
- cell arrest
- DNA repair
- apoptosis
- senescence
what are the main two tests for prostate cancer?
1) Direct Rectal Exam (but does not detect microscopic tumour)
2) Prostate Specific Antigen
