Neoplasms, carcinogenesis and tumour classification Flashcards
What is neoplasia?
Unregulated and irreversible clonal growth that results in neoplasm/tumour formation
Why is neoplasia described as unregulated and irreversible?
Neoplasia continues after stimulus is removed
What is a neoplasm/tumour?
Lesion formed by abnormal autonomous growth of cells that persists in absence of a stimulus
What is meant by clonal growth to form a neoplasm/tumour?
All of the tumour cells are derived from the same single cell of origin
What are the 2 types of neoplasm/tumour?
Benign or malignant
What cell types can undergo neoplastic change?
All cell types
What is the most common cell type that undergoes neoplastic change?
Epithelial cell
What 2 factors can cause molecular change of genes in carcinogenesis?
Mutagens
Ageing
What are the 2 types of genetic change in carcinogenesis?
Genetic mutation
Epigenetic change
What is epigenetic change?
Modification of genes due to environment and behaviours eg. methylation
Gene sequence itself isn’t altered
What properties do genetic errors provide to cells in carcinogenesis?
Cancer hallmarks
How many cancer hallmarks are there?
6
What are the 6 cancer hallmarks of cancer cells developed in carcinogenesis?
Resisting apoptosis
Constant proliferation
Inducing angiogenesis and immune system evasion
Enabling replicative immortality
Evading growth suppressors
Activating invasion and metastasis
What 2 characteristic features of a cancer can be identified by examining its cancer hallmarks?
Natural history
Responses to therapies
When genetic error occurs in carcinogenesis, is this a type of DNA damage?
Yes
How is a mutagen different from a carcinogen?
Mutagens can be non-lethal, but carcinogens usually result in malignant tumours (cancer)
What is a carcinogen?
Agent that causes DNA damage that increases cancer risk
Give 2 examples of chemicals that are carcinogens?
Benzene
n-nitrosamine
Why is cigarette smoke a carcinogen?
It contains benzene
What bacteria is associated with gastric adenocarcinoma and lymphoma?
Helicobacter pylori
What type of infective agent is a liver fluke, that is also a carcinogen?
Parasite
Give 4 examples of oncogenic viruses?
HPV, EBV, HCV, HBV
Give 4 types of cancers that radiation is associated with?
Skin cancer, thyroid cancer, lymphoma, leukaemia
How is a clone of neoplastic daughter cells formed in carcinogenesis?
The cell which has undergone DNA damage overcomes DNA repair mechanisms and can transmit the genetic error to daughter cells, forming a clone
What occurs in progression during the molecular sequence of carcinogenesis?
A single daughter cell from the clone mutates to have a survival advantage, so natural selection favours this aggressive daughter cell and it dominates the population by forming its sub-clone
How does a tumour form a tumour microenvironment?
The tumour recruits normal cells
Where does a tumour form its tumour environment?
In the organ that it arises from
How do DNA mutations cause tumour growth, invasion of surrounding tissues and metastasis?
DNA mutations disrupt regulatory systems
What is the most commonly mutated proto-oncogene in the human body?
RAS (Rat Sarcoma virus)
What is a proto-oncogene?
Normal gene for cell growth and differentiation, that mutates into an oncogene
Give 5 examples of proto-oncogenes?
Growth factor
Growth factor receptor
Nuclear receptor
Cell-cycle receptor
Signal transducer
What does MAP Kinase pathway stand for?
Mitogen-Activated Protein Kinase pathway
What type of receptor does the growth factor bind to at the cell membrane in the MAP Kinase pathway?
Receptor tyrosine kinase
What inner membrane protein is activated by binding of growth factor to receptor tyrosine kinase in the MAP Kinase pathway?
RAS (Rat Sarcoma virus)
In the MAP Kinase pathway, what molecule does RAS activate, and what it its function?
RAF (Rapidly Accelerating Fibroma), a signal transducer
In the MAP Kinase pathway, what molecule does RAF activate, and where is is found in the cell?
MEK, a cytoplasmic protein
In the MAP Kinase pathway, what molecule does MEK activate?
ERK
In the MAP Kinase pathway, what does ERK do after it travels to the nucleus?
Activates transcription factors controlling cell metabolism and growth
In the MAP Kinase pathway, how do the ERK-activated transcription factors affect cell-cycle proteins?
Cell-cycle proteins are switched off
When cancer arises, what step of the MAP Kinase pathway is different?
Cell-cycle proteins mutate to be permanently switched on, which causes uncontrollable transcription
What is the role of Her 2 in the MAP Kinase pathway, and what type of cancer is it amplified in?
Her 2 is a receptor tyrosine kinase that is amplified in breast cancer
What drug is given to inhibit Her 2 when it is amplified in breast cancer?
Herceptin
What type of drug is used to treat malignant melanoma, which involves the MAP Kinase pathway?
RAF inhibitor
What are tumour suppressor genes?
Genes that regulate cell growth by preventing tumour development
What hypothesis is used to explain how tumour suppressor genes are affected by DNA mutations and cause cancer?
Knudson’s two hit hypothesis
Explain how Knudson’s two hit hypothesis refers to mutated tumour suppressor genes in carcinogenesis?
Both maternal and paternal copies of the tumour suppressor gene must be mutated to cause cancer
What triggers p53 expression in a normal cell?
DNA damage
What does p53 activate to stop the cell-cycle at the G1 checkpoint?
p53 activates transcription factors to form CDKI p21, which blocks the CDK4/cyclin D, this stops cell-cycle progression
How does p53 trigger apoptosis when the cell has severe DNA damage?
Upregulates BAX, which disrupts BCL2 so that the mitochondrial membrane loses its stability and cytochrome C leaks out
What is retinoblastoma?
Tumour suppressor gene that regulates progression from G to S phase of cell-cycle
What are apoptosis regulators?
They stop normal cells from dying but promote apoptosis in mutated cells with irreparable DNA damage
How does BCL2 stabilise the mitochondrial membrane?
Blocks release of cytochrome C
In follicular lymphoma, what chromosome mutation has occured?
Translocation of BCL2 gene from chromosome 18 to Ig heavy chain locus of chromosome 14
In follicular lymphoma, how does the translocation of BCL2 gene cause enhanced stability of the mitochondrial membrane?
BCL2 is overexpressed
In follicular lymphoma, what is the cancer hallmark produced by the enhanced mitochondrial membrane stability?
Malignant lymphocytes are immortal
What is the macroscopic feature of follicular lymphoma?
Rubbery enlarged lymph nodes
What is the characteristic microscopic feature of follicular lymphoma?
Large, pale nodules in lymph node called malignant lymphoid follicles
What is the function of telomerase in normal cells?
Elongates telomeres, which are pieces of DNA that shorten with serial cell division and lead to cell senescence
How is telomerase different in cancer cells?
Telomerase is upregulated
How do cancer cells evade the immune system?
They produce factors that switch off the immune system
What is the importance of angiogenic factors in carcinogenesis?
They form new blood vessels which are needed for tumour growth
Give 2 examples of angiogenic factors used for tumour growth?
Fibroblast growth factor
Vascular endothelial growth factor
Where are benign tumours located relative to their area of origin?
Remain localised to area of origin
How can the growth rate of a benign tumour be compared to the growth rate of a malignant tumour?
Benign tumour has slow growth rate but malignant tumour has fast growth rate
What is meant by malignant tumours being invasive?
Malignant tumours can directly enter surrounding tissues and travel to distant sites, which is metastasis
To what extent do benign tumours resemble their origin tissue?
Closely resemble their origin tissue
What are 2 ways in which malignant tumours can resemble their origin tissue?
Well-differentiated malignant neoplasms closely resemble origin tissue
Poorly-differentiated malignant neoplasms don’t closely resemble origin tissue
Are benign tumours encapsulated, and what does this mean?
Benign tumours are encapsulated, so they are compact and confined to a specific area
Are malignant tumours encapsulated or not?
No, they have irregular margins, so they aren’t compact and aren’t confined to a specific area
Give one example of a malignant tumour that doesn’t usually metastasise?
Basal cell carcinoma, a malignant skin cancer
Describe the nuclear to cytoplasmic ratio in benign cells compared to malignant cells?
In benign cells there is a low nuclear to cytoplasmic ratio
In malignant cells there is a high nuclear to cytoplasmic ratio
Why do malignant cells have a high nuclear to cytoplasmic ratio?
They have nuclear pleomorphism (irregularities in nuclear shape and size), which makes the nuclei very large
Why do benign cells have a low nuclear to cytoplasmic ratio?
They don’t have nuclear pleomorphism, so all nuclei are similar size
Do malignant and benign cells have hyperchromasia?
Malignant cells have hyperchromasia
Benign cells don’t have hyperchromasia
What is hyperchromasia?
Stained nucleus appears dark, opaque, smudged
How is chromatin distributed in benign cells compared to malignant cells?
In benign cells, chromatin is distributed evenly
In malignant cells, chromatin is distributed irregularly and is vesicular/clumped
Do benign and malignant cells have distinct nucleoli?
Benign cell has no distinct nucleolus
Malignant cell might have distinct nucleolus
Describe the nuclear membranes in benign cells compared to in malignant cells?
Smooth nuclear membrane in benign cell
Irregular nuclear membrane in malignant cell
What is dysplasia?
Disordered growth that is the precursor to carcinoma (malignant tumour of epithelium)
Is dysplasia reversible?
Potentially, if stressors are removed in early dysplasia
Why does dysplasia become irreversible carcinoma?
Stressor persists
What 2 long-standing conditions does dysplasia arise from?
Metaplasia, hyperplasia
What is another name for dysplasia?
Intraepithelial neoplasia
What is Barrett’s oesophagus?
Metaplastic change of stratified squamous epithelial cells of lower lining into simple columnar epithelium cells that compose glands
How can Barrett’s oesophagus result in dysplasia?
Glands become more abnormal and undergo dysplasia
What kind of dysplasia can endometrial hyperplasia lead to?
Cervical intraepithelial neoplasia
How can you obtain a sample of cells from the outer surface of the cervix to test for dysplasia?
Smear test, where cells on surface are brushed off
What is dyskaryosis?
Abnormal change in squamous epithelial cell characterised by irregular chromatin and hyperchromasia
What is pyknosis?
Irreversible condensation of chromatin in nucleus of cell undergoing apoptosis/necrosis
In cells of cervical dysplasia, would there be dyskaryosis, and why?
Yes, because they are stratified squamous epithelial cells
What classification system is first used to classify a tumour?
Histogenic classification
Why is histogenic classification important when classifying and identifying the origin of a cancer?
Different cell types can develop different tumours
What are the 4 main classes of origin cell types in histogenic classification of cancers?
Lymphocyte, Haematopoietic cell, epithelial cell, connective tissue/mesenchymal cell
Give 4 examples of tumours derived from epithelial cells?
Carcinoma
Adenoma
Adenocarcinoma
Squamous cell carcinoma
What is a carcinoma?
Malignant tumour derived from epithelial cells
What is a squamous cell carcinoma?
Malignant tumour derived from squamous epithelial cells
What is an adenoma?
Benign tumour derived from epithelial cells that shows gland formation
What is an adenocarcinoma?
Malignant tumour derived from epithelial cells, of glandular origin or showing gland formation
How can you tell from the name of a tumour derived from epithelial tissue, if it is malignant or benign?
Malignant ends in ‘carcinoma’
Benign ends in ‘oma’
Give 2 microscopic features of a squamous cell carcinoma?
Desmosomes linking tumour cells
Keratin production (pink material)
Give 2 microscopic features of an adenocarcinoma?
White lumen of malignant glands
Mucin in cytoplasm
How can you tell from the name of a tumour derived from connective/mesenchymal tissue, if it is malignant or benign?
Malignant tumour ends in ‘sarcoma’
Benign tumour ends in ‘oma’
What are the names of malignant and benign tumours derived from adipose tissue?
Malignant: liposarcoma
Benign: lipoma
What are the names of malignant and benign tumours derived from blood vessels?
Malignant: angiosarcoma
Benign: haemangioma
What are the names of malignant and benign tumours derived from skeletal muscle?
Malignant: rhabdomyosarcoma
Benign: rhabdomyoma
What are the names of malignant and benign tumours derived from smooth muscle?
Malignant: leiomyosarcoma
Benign: leiomyoma
What are the names of malignant and benign tumours derived from schwann cells?
Malignant: Malignant Peripheral Nerve Sheath Tumour
Benign: schwannoma
What are the names of malignant and benign tumours derived from fibroblasts?
Malignant: fibrosarcoma
benign: fibroma
What is a lymphoma?
Malignant tumour derived from lymphocytes, that is commonly found in lymph nodes and enlarges them
How does a lymphoma relate to lymph nodes?
Lymphoma commonly found in lymph node and causes it to have enlarged appearance
When a malignant tumour derived from lymphocytes is leukaemia, where is it found?
Peripheral blood or bone marrow
What is the malignant tumour derived from haematopoetic cells?
Leukaemia
Give 2 microscopic features of follicular lymphoma?
Oval pale nodules that are malignant lymphoid follicles
Medullary sinuses can’t be seen anymore
What characteristic feature does the blood film of chronic lymphocytic leukaemia (CLL) show?
Small lymphocytes
What is tumour grade?
How closely a tumour resembles the origin tissue
How do you interpret high and low tumour grades?
The higher the grade, the more poorly differentiated the tumour is (resembles origin tissue less), so the tumour is more aggressive and spreads more rapidly
In a grade 3 tumour, how can you identify the origin tissue?
Immunohistochemistry, where antigens from the tumour are identified by observing their colour reactions with specific, labelled antibodies
In normal breast tissue, what structures are found in the lobes?
Lobules, which are composed of acini (glands) that have epithelial lining and open lumen
In a grade 1 breast adenocarcinoma, what would you see in the microscopic image?
Well-differentiated and acini resemble those of normal breast tissue
In a grade 3 breast carcinoma, what would you expect to see in the microscope image?
Poorly-differentiated and no acini
What is the most common malignant tumour found in breast tissue?
Adenocarcinoma
What is tumour stage?
Extent of tumour spread
What system is used to determine the tumour stage?
TNM system 8th edition
What 3 types of examinations are needed to determine tumour stage?
Pathological, radiological, clinical
What does T represent in the TNM system 8th edition?
Size/extent of local invasion of primary tumour
What does N represent in the TNM system 8th edition?
Whether metastasis to lymph node has occurred, which drains parent organ of tumour
What does M represent in the TNM system 8th edition?
Whether metastasis to distant site has occurred
In oesophageal cancer, when does T score of TNM system increase?
With increasing involvement of layers of oesophageal wall
In oesophageal cancer, when does N score of TNM system increase?
With increasing number of positive lymph nodes (lymph nodes that have cancer)
