Tumour pathology Flashcards
What is a tumour?
Abnormal growing mass of tissue, who’s growth is uncoordinated with the surrounding normal tissue
What is a neoplasm?
A tumour
What are the 2 types of tumours?
Benign and Malignant
Which type of tumour more harmful?
Malignant (cancer)
Benign is only really ever harmful if it grows in a key physiological structure
What is metastasis?
Spreading of cancer to other sites within the body
What are the 5 most common types of cancer (in the UK)?
Breast Lung Prostate Colon Melanoma
Which common form of cancer is most dangerous?
has lowest 5 year survival percentage
Lung cancer
10%
Tumours are classified depending on their type and where they are.
What is different between classifications of tumours?
Behaviour
Treatment route
What is the most common site (tissue) of origin for tumours to form?
Epithelial tissues
What is the name given to a malignant tumour in epithelial tissue?
Carcinoma
What type of tumour is an adenoma?
Benign tumour in the glandular epithelium
What is the name given to a malignant tumour in connective tissue?
What would one in fat be called?
Sarcoma
Lipo-sarcoma
What is the name given to a benign tumour in bone?
Osteoma
What is the name given to a benign tumour in white blood cells?
Prankd
Does not exist
Classify leukaemia as a type of tumour.
Malignant
White blood cells
Classify lymphoma as a type of tumour.
Malignant
Lymphoid tissue
What are Naevi?
Benign
Melanocytes
What is the name given to a malignant tumour of the melanocytes?
Melanoma
Give 2 examples of malignant tumours that originate in neural tissues.
Astrocytoma:
- Astrocytes
- CNS
Schwannomia:
- Schwann cells
- PNS
Describe what teratomas are, and the differences in them, based on gender.
Tumour of germ cells
In males (testes), they are usually malignant + can easily migrate to other areas/metastasise
In females (ovaries), they are (usually) benign
Describe the features of benign tumours in terms of:
- Growth pattern
- Encapsulation
- Invasion
- Metastases
- Differentiation
- Function
- Behaviour
- Non-invasive
- Usually encapsulated
- Non-invasive
- No metastasis
- Well-differentiated
- Function similar to normal tissue
- Rarely cause death
Describe the features of malignant tumours, considering:
- Growth
- Encapsulation
- Metastasis
- Differentiation
- Function
- Behaviour
- Invasive growth
- No capsule or capsule breached by tumour cells
- Poorly differentiated
- Abnormal appearance
- Loss of normal function
- Usually metastasises
- Frequently causes death
What are the local effects of benign tumours?
Pressure
Obstruction
What are the local effects of malignant tumours
Pressure
Obstruction
Tissue destruction - ulceration/infection
Bleeding - anaemia/haemorrhage
Pain - pressure/infiltration of nerves/pathological fractures of bone
Effects of treatment
What are systemic effects of malignant tumours
Weight loss (cancer cachexia)
Hormone secretion*
Paraneoplastic syndromes
Effects of treatment
Describe the different types of hormone production by tumours*
Can be ‘normal’, when the tumour is of an endocrine organ. This normally produces the hormone, but will have abnormal control of hormone production
Abnormal/Inappropriate - when hormones are produced by a tumour in an organ that does not normally produce hormones
What is a paraneoplastic syndrome?
A syndrome that is the consequence of cancer in the body but is not due to the local presence of cancer cells
(ie - it is not due to the pressing of the tumour on something)
What is dysplasia?
A pre-malignant change/abnormality in cells
Cells with this change can progress to cancer
Earliest stage of progression to malignancy that can be identified
What are the features of dysplasia, that can be identified when microscopically viewed?
Increased nuclear size
Increased mitotic activity
Abnormal mitoses
General disorganisation of cells
What is the difference between high grade dysplasia, and low grade dysplasia
High grade = close to malignancy - more worrying
Describe the cell cycle of a cell that divides by mitosis
G1 - synthesis of components for DNA synthesis
S - DNA synthesis
G2 - preparation for mitosis
M - mitosis
(+ G0)
What factors control the cell cycle?
External factors - hormones, growth factors, cytokines and stroma
Intrinsic factors - revolve around checkpoints
What is the restriction point?
Point in the cell cycle, prior to which, progress through G1 phase was controlled by external factors
After R, progress through cell cycle becomes autonomous, and is controlled by intrinsic factors (checkpoints)
What is the G0 phase?
Quiescent phase
Resting phase - cell has left cycle and does not divide
Checkpoints in the G1 phase will cause G1 arrest if…
If the cell lacks components needed for S phase
If the cell size is inadequate
If there is an inadequate nutrient supply
If essential external stimuli are lacking
If DNA damage is detected
Checkpoints in S phase cause arrest if…
If DNA is not replicated
Checkpoints will cause G2 arrest if…
If cell size is inadequate
If DNA damage is detected
The checkpoint in M phase will cause arrest if…
If there is chromosome mis-alignment
ensures cell is ready to complete division
What stage of mitosis is the M phase checkpoint in?
Metaphase
What are the 2 main components of a checkpoint?
Cyclin-dependent kinases (CDKs) - catalytic subunits
+
Cyclins - regulatory subunits
These together form a CDK/cyclin complex, where the cyclins regulate the CDKs
What is the basic function of CDK/cyclin complexes, when acting on target proteins?
Phosphorylate
This activates/inactivates the target substrate
The substrates regulate events of the next phase of the checkpoint cycle
Aside from cyclins, what else regulates CDKs
CDK inhibitors (CKIs)
These bind to cyclin/CDK complexes and inhibit stuff
What are the 2 families of CKIs
INK4A
CIP/KIP
pRb is a phosphoprotein encoded by the retinoblastoma gene (an anti-oncogene)
pRb becomes active (Rb) when…
Hypophosphorylated
Inactive (pRb) when phosphorylated
What is the effect of pRb when activated?
Active Rb stops cell cycle progression
Active Rb binds to E2F transcription factor
pRb (inactive) loses affinity for E2F - which becomes ‘free’
Free E2F transcription factor activates vital target genes - stimulating entry to/progression of the cell cycle
What is carcinogenesis?
Initiation of cancer formation
What are DNA adducts?
Products of reaction between chemical carcinogens and DNA
Adduct formation at particular chromosome sites causes cancer
Why is a mutation in the retinoblastoma gene potentially dangerous?
Absent or non-functional/inactive pRb releases the cell cycles brake
= uncontrolled proliferation
What is P53?
Type of cell cycle regulator
Describe how P53 works
Damage to cell causes P53 levels to rise
High P53 levels either;
- induces cell cycle arrest at G1
- Triggers DNA repair
- P53 induced apoptosis - severe damage
Why is mutation in the P53 gene dangerous?
Cells with mutated p53 will not G1 arrest, repair DNA or undergo p53 induced apoptosis
Describe the differences between the sporadic and inherited mutations of anti-oncogenes
Sporadic - two point mutations of anti-oncogene occur in a single cell
Inherited - In order to have an effect, must have one inherited mutated gene and one somatic point mutation
(both alleles of anti-oncogene must be mutated for cancer to arise)
What is an oncogene
A gene which under certain circumstances can transform a cell into a cancer cell
This can occur for 2 reasons:
- Alteration of proto-oncogene structure
- Dysregulation of proto-oncogene expression
What types of proteins are coded for by proto-oncogenes
Growth factors
Growth factor receptors
Signal transduction proteins
Nuclear regulatory proteins
Cell cycle regulators
What DNA viruses are known viral carcinogens?
HPV
Hepatitis B
EBV
How do chemical carcinogens cause cancer?
Chemical reacts with DNA and forms adducts
Adducts at particular chromosome sites lead to activation of oncogenes and suppression of anti-oncogenes
What are the main types of tumour biomarkers?
Onco-fetal proteins
Oncogenes
Growth factors and receptors
Immune checkpoint inhibitors
What are onco-fetal proteins?
Proteins normally present during fetal development but are found in adults with certain types of cancer
What is the main onco-fetal protein, and what it is a biomarker of?
Alpha fetoprotein
Biomarker of:
- teratoma in the testes
- hepatocellular carcinoma
What is Kras?
Predictive biomarker for colorectal cancer
What is Braf?
Predictive biomarker for melanoma
What is EGFR?
Predictive biomarker of lung cancer
What is PD-L1?
Predictive biomarker of lung cancer
What is Her2?
Predictive biomarker of Breast cancer and gastric cancer
