Behaviour of Tumours Flashcards
1
Q
What are the two genetic mechanisms that could cause cancer?
A
Mutation in a stimulatory gene e.g. cells growing and dividing - protooncogene -> oncogene
Mutation in inhibitory genes e.g. repairing DNA mistakes - tumour suppressor gene
2
Q
Which factors are important in tumorigenic mechanisms?
A
- Parallel pathways exist
- Variable in cancer types and subtypes:
1. Order that mutations occur
2. Which mutations occur - Certain mutations may decrease the number of steps required to complete tumorigenesis
- Case 1
o p53 loss – angiogenesis and resistance to apoptosis and genetic instability (5 steps) - Case 2
o Two or more genetic changes required
o For invasion/metastasis and resistance to apoptosis (8 steps)
3
Q
Which mutation causes hyperplasia?
A
Mutation APC
4
Q
Which mutation causes adenoma (polyps)?
A
Mutation K-RAS
5
Q
Which mutation causes adenoma to progress to adenocarcinoma (colon cancer)?
A
Deletion p53
6
Q
What can other mutations cause adenocarcinoma to progress to?
A
Metastatic cancer
7
Q
What are cancer stem cells and what are their properties?
A
- Small unique population of different cells with self renewal potential in order to produce the variety cells that form the tumours
- These cellular combinations are called cancer stem cells because of their stem like properties in comparison with stem cells
- Remarkable properties of these cells comprise extensive ability to differentiation and also self renewal
8
Q
What is the cancer stem cell hypothesis?
A
Mutations acquired which reactivate genes responsible for increased proliferative activity, cell-division and differentiation
9
Q
How does the clonal evolution model link to origin of tumour heterogeneity?
A
Clonal evolution model states that CSCs can be generated from differentiated mammary cells by dedifferentiation process
Tumour heterogeneity increases as a result of the formation of intra-tumoral clones by the sequential mutations
10
Q
How are tumours classified? What are the three critical determinants?
A
- Clear histopathological classification of tumours is essential for diagnosis and clinical management
- This involves using morphological and molecular features
- Three critical determinants:
o Differentiation states
o Embryonic and normal origin of the cell/tissue
o How the cell behaves (benign or malignant)
11
Q
What are the three types of differentiation states?
A
Epithelial
Non-epithelial
Mixed
12
Q
What are the three embryonic orgins?
A
Ectoderm
Endoderm
Mesoderm
13
Q
What are the two biological behaviours of tumours?
A
Benign
Malignant
14
Q
What is the histogenetic origin of tumours?
A
- Tumours are derived from specialised cell types
- Depending on the (the tissue or cell type from which the tumour arose) it can generally be divided into epithelial and mesenchymal types (~1% tumours)
15
Q
What are the two major categories of carcinomas which reflect two major functions of the epithelia?
A
- Covering and Lining Epithelia
o Forms the surface of the skin and some internal organs
o It forms the inner lining of ducts and body cavities and the interior of the respiratory, digestive, urinary and reproductive systems – stratified squamous - Glandular Epithelia
o Are found in organs such as the thyroid, adrenal glands and sweat glands
o And glands in breast and prostate
o Specialised polarised cells which secrete into ducts or cavities – simple cuboidal and simple columnar
16
Q
Which epithelia are derived from which germ layers of the embryo?
A
Ectoderm:
Skin epidermis
Glandular tissue of breast
Mesoderm:
Ovaries
Endoderm: Lungs Liver Gall bladder Pancreas Stomach Intestine
17
Q
What proportion of human cancers are epithelial in origin (carcinomas)?
A
- > 80% cancer-related deaths in Western world
1. Producing recognisable squamous cells: squamous cell carcinoma (nasal cavity, larynx, lung, cervix, skin)
2. Glandular growth pattern: adenocarcinoma (lung, colon, breast, pancreas, stomach prostate)
18
Q
What is the nomenclature of a benign tumour?
A
- Suffix – oma to the cell of origin
- Name of cell origin + morphological character + oma
- E.g. tumours of squamous epithelium – squamous cell papilloma (soft fibroma on eyelid)
19
Q
What are examples of benign epithelial tumours?
A
- Adenoma: tumour forming glands
- Papilloma: tumour with finger-like projections
- Cystadenoma: cystic tumour in ovary
- Papillary Cystadenoma: papillary pattern in cystic tumour forming glands
- Polyp: tumours tat projects above the mucosal surface
20
Q
What is the nomenclature of malignant tumours?
A
- Name of origin of cell + morphological character + sarcoma/carcinoma
- Description/name depends on the tissue of origin:
o Epithelial -> carcinoma
o Mesenchymal -> sarcoma - E.g. a malignant tumour of the prostate is prostate (tissue) adenocarcinoma (glandular epithelium) or an adenocarcinoma of the prostate
- Other malignant tumours:
o Hematopoetic -> Leukaemia/lymphoma/myeloma
o Neuroectodermal -> Glioma/neuroblastoma
o Embryonic (immature tissue) -> Blastoma
21
Q
What is the difference between benign and malignant tumours?
A
- Benign tumours are NOT cancer
o Remain localised to the tissue from which they arise
o Curable by surgery (BUT can compress vital organs e.g. meningioma in the CNS)
o Grow by expansion - Malignant tumours ARE cancer
o Grow by expansion and infiltration
o Tumour cells become detached and extend through the adjacent tissues
o May be carried away by the lymph to local lymph node and to more ditant organ such as liver or lungs OR spread directly through the bloodstream – metastasise
o Surgical resection becomes difficult - Invasive/basement membrane breached
- Non-encapsulated (often irregular shape)
22
Q
What are the characteristics of cancer cells?
A
- Cancer cells are not under normal cell growth controls – immortal:
o Cell division is high
o Centre of tumour does not receive sufficient food and oxygen
o Ischemic necrosis
o Shedding or loss of tumour cells - Dead cells appear as apoptotic figures
- Both normal and abnormal mitotic figures seen in dividing cells – tumour growth
23
Q
What are the degrees of tumour differentiation?
A
- Well-differentiated neoplasm
o Resembles mature cells of tissue of origin - Poorly differentiated or undifferentiated neoplasm
o Composed of primitive cells with little differentiation
o Rate of growth of malignant tumour directly proportionate to the degree of differentiation
o Aggressive growth pattern - Correlation with biologic behaviour
o Benign tumours are well differentiated
o Poorly differentiated malignant tumours usually have worse prognosis
24
Q
What is involved in well-differentiated squamous cell carcinoma of the skin?
A
- Malignant squamous cells grow in all directions
- Invading cells retain ability to synthesise keratin and keratin is often trapped inside the tumour – ‘keratin pearls’
25
What is the natural history of malignant tumours?
1. Malignant change in the target cell, referred to as transformation
2. Growth of the transformed cells
3. Local invasion
4. Distant metastases
26
How is malignancy characterised by metastasis?
- Metastasis complex process
1. Vascularisation of tumour occurs
2. Cells detach from the primary tumour
3. Basement membrane is degraded and invasion into the ECM occurs
4. Intravastion of nearby blood vessels
5. Tumour cells circulate in the vascular system
6. Some cells adhere to the walls of blood vessels
7. Extravastion and migration to local tissue occurs
8. Where secondary tumour can form
- Haematogenous dissemination
- Lymphatic dissemination
27
What is the significance of nodal metastasis?
- Example: breast cancer
o A modified radical mastectomy removes the entire breast – including the breast tissue, skin, areola and nipple – and most of the underarm (axillary) lymph nodes which most common site for metastasis
- Prognostic
o Number of involved nodes is an important component of the TNM staging system
- Therapeutic
o Overall risk of recurrence
o Extent of nodal involvement
o Histological grade and other considerations
o Adjuvant therapy
28
How are tumours graded?
- Grading
1. Degree of anaplasia (degree of differentiation)
2. Rate of growth
o Numeric grade describes tumour based on how abnormal the cells and tissue look under a microscope
o Indicator of how quickly a tumour is likely to grow and spread
o Well-differentiated – tumours tend to grow and spread at a slower rate than undifferentiated tumours
o The factors used to determine tumour grade can vary between different types of cancer
o Grade – I
Well differentiated (< 25% anaplastic cells)
o Grade –II
Moderately differentiated (25-50% anaplastic cells)
o Grade –III
Moderately differentiated (50-75% anaplastic cells)
o Grade- IV
Poorly-differentiated or anaplastic (>75% anaplastic cells
o GX means that the grade can't be assessed.
It is also called undetermined grade.
o Some cancers have their own grading system
E.g. Prostate cancer Gleason Score
29
How are tumours staged?
1. Size of tumour
2. Extent of growth (or spread)
o Cancer stage refers to the size and/or extent (reach) of the (primary) tumour
o Whether or not cancer cells have spread in the body
o Based on factors such as:
Location of the primary tumour
Tumour size regional lymph node involvement
Number of tumours present
o Two types:
1. Tumour Nodes Metastasis (TNM)
2. Number system
o T - size of the cancer and how far it has spread into nearby tissue
o N refers to whether the cancer has spread to the lymph nodes – it can be between 0 (no lymph nodes containing cancer cells) and 3 (several lymph nodes containing cancer cells)
o M refers to whether the cancer has metastasised – it can either be 0 (no spread) or 1 (the cancer has spread)
o Tx Tumour size cannot be assessed
30
What are paraneoplastic syndromes?
- Clinical syndromes not caused by direct invasion or metastasis of tumour which accompany malignant disease
- Non-metastatic manifestation of malignant disease
- Vary in functional impact and clinical presentation
- The most common associated malignancies include small cell lung cancer, breast cancer, gynaecological tumours and haematological malignancies
- Arise from tumour secretion of:
o Hormones
o Peptides
o Cytokines
(these 3 interfere with normal metabolic pathways)
o Immune cross-reactivity between malignant and normal tissues
- Four categories depending on the organ system involved:
o Endocrine
o Neurologic
o Dermatologic and rheumatologic
o Hematologic
31
What are examples of paraneoplastic syndromes and what are they caused by?
Hormones -> Endocrone paraneoplastic syndromes -> Cushing Syndrome
Functional peptides -> Endocine paraneoplastic syndromes -> Hypoglycaemia
Cytokines -> Haematologic paraneoplastic syndromes -> thrombocytosis
Antigen -> B cell -> Antibody secretion (e.g. anti-AChR)/autoimmune response) -> Normal cell of CNS/neurologic paraneoplastic syndromes -> Myasthenia gravis
32
Summarise characteristics of tumours.
1. Disobey growth signals – proliferate rapidly
2. Escape from death signals – immortality
3. Imbalance between cell proliferation and growth- excessive growth
4. Contain cancer stem cells which vary in origin and produce cells with distinctive genotypes
5. Lose differentiation ability – no function
6. Are instable – accumulate mutations
7. Overrun the neighbouring tissue- invade locally
8. Have the ability to travel from the sight of origin to another part of the body – distant metastasis
