Neoplasia 2 Flashcards
What are the two components of tumours
Neoplastic cells that constitute the tumour parenchyma
Reactive stoma made up of connective tissue, blood vessels and cells of the adaptive innate immune system
What is a benign tumour that originates from squamous epithelium called
Papilloma
What is a benign tumour called that originates from glandular epithelium (salivary)
Adenoma
What is a malignant tumour that originates from the glandular epithelium called
Adenocarcinoma
What do epithelial tumours names end in
Oma or carcinoma
What do tumours of connective tissues names end in
Sarcoma
What is a malignant tumour from a lymphoid tissue called
Lymphoma
What is a malignant tumour from haemopoietic tissue called
Leukaemia
What is leukoplaskia
White patch that cannot be rubbed off or attributed to any other cause
Benign tumours have the potential to…
Become malignant
How do you find out if a benign tumour has the potential to become malignant
Take a biopsy and pathology labs can look for dysplasia
What can dysplasia effect
Various epithelial tissues
What is dysplasia identified by
Identified by changes in cells -
- appearance
- arrangement
Name some risks of oral cancer
- tobacco
- chewing habits
- alcohol
- diet and nutrition
- oral hygiene
- viruses
- immunodeficiency
- socioeconomic factors
- GORD (acid reflux)
What viruses are associated with cervical cancer and oral cancer
HPV 16 and 18
What is carcinogens
- benign tumours
- malignant tumours - chemical agents, physical agents, viruses, may affect tissue directly or indirect effect on other tissues
What are the three stages for carcinogenesis
- initiation
- promotion
- progression
Describe the initiation phase
- when a carcinogen induces a genetic change resulting in neoplastic potential
What is promotion
Another factor stimulates the initiated cell for division (clonal proliferation) does not act on non-initiated cells for division
What is progression
Additional mutations resulting in malignancy
What are some chemical carcinogens
- smoking polycyclic hydrocarbons including tars
- diet, drugs and alcohol
- asbestos
What are physical carcinogens
- ionising radiation (damages DNA, causing mutations)
- radioactive metals and gases
Radium - bone and marrow tumours
What is the least sensitive to radiation sensitivity
Muscle tissue and nerve tissue
What is the most sensitive tissue to radiation
- embryonic tissues
- spleen, bone marrow
What type of carcinogen is UV light
Physical carcinogen
What are viral carcinogens
- DNA viruses
- RNA viruses
What are the two main factors in carcinogenesis
- genetic
- enviromental
Name some important genes in carcinogenesis
- oncogenes
- tumour suppressor genes
- DNA repair genes
- MiRNAs
- chromosomal aberrations
- epidemic mutations
What are oncogenes
Proto-oncogenes are normal genes which regulate cell division
Abnormal variants are oncogenes
They produce oncoproteins
What is the effect of oncogenes
- mutation
- excess normal product
- enhanced transcription
What is the function of tumour suppressor genes
Brakes
They act to inhibit cell division and suppress growth
Act as anti oncogenes
- all require loss of both alleles
- retinoblastoma gene
How many genes need to be knocked out/mutated for tumour suppressor genes and oncogenes
Oncogenes - 1 gene
Tumour suppressor - 2 genes
What is P53
The guardian of the genome
Acts just before the restriction point (cell cycle)
2 main functions in response to damaged DNA
Often inactivated in cancer
What are the 2 ways p53 responds to damaged DNA
Stops and allows DNA repair
Apoptosis
What is the action of HPV
Blocks p53 therefore mutated genes are carried on
Describe inherited cancer synodromes
- single mutant genes, often tumour suppressor genes
- retinoblastoma, some colon cancers
Describe familial cancer
- family clusters
- genes and pattern of inheritance not clear
- breast, ovary and colon
What is defective DNA repair
- increased sensitivity to carcinogens and general increased cancer risk
- xeroderma pigmentosum
What are the hallmarks of cancer
Ability to evade anti growth signals
Provide their own growth signals
Evading apoptosis
Tissue invasion and metastatsis
Limitless replicative potential
Sustained antiogenesis
What are some modes of spreading for malignant tumours
- local spread
- lymphatic spread
- blood spread (haematogenous)
- transcoelomic spread
- intraepithelial spread
What is metasis
Spread of the malignant cells to distant organs for morning secondary tumours
What is the pattern of spread for carcinomas
- lympathic
- blood (often later)
What is the pattern of spread for sarcomas
- blood (lymphatic spread rare)
Explain some predictable patterns of spread
- lung to local nodes, liver, bone and brain
- tongue to neck nodes, later lung and spine
Explain the grade of the tumour
Biological nature of the tumor
Histolopathology
Explain stage in tumours
Extent of the spread (clinical)
What does cancer staging provide
Describes the extent or severity of a persons cancer, knowing the stage helps for planning treatment and prognosis
Describe the clinical staging of oral cancer
TNM system is used for oral cancer
T - tumour size
N - lymph node involvement
M - metastases
Immunotherapy
• • •
Active immunisation.(HPV, Hep B) Reversal of immunosuppression Adopted cell transfer (ACT)
Tumour- infiltrating lymphocytes (TILs)
CAR T-cell therapy- haematological malignancies
• Strengthening natural immune responses-research still needed.
Escape
Cells may acquire molecular changes such as:
• Alter tumour antigen expression . Lack of T-cell recognition
• Activation of immunoregulatory pathways leading to T-cell unresponsiveness and apoptosis.
• Immunosuppressive factors eg. cytokines (TGF-β). Inhibit T-cell response
Elimination
Cell mediated immune response
• Cytotoxic T-lymphocytes (CD8+)
• Natural killer cells. First line of defence against tumour cells.
• Macrophages. Mechanisms similar to anti-microbial killing.
Immunodeficiency states can lead to an increased incidence of malignant tumours
Elimination quickly moves to escape
How does the immune system recognise tumour cells
Tumour associated antigens (TAAs); neoantigens
• Products of mutated genes
• Overexpressed proteins (tyrosinase)
• Viral proteins (HPV,EBV)
• Oncofetal antigens (carcinoembryonic antigen)
• Others
Grading involves histological assessment of
• Invasion into underlying tissue
• Cellular atypia : abnormal mitotic activity, nuclear pleomorphism, differentiation, necrosis
• Various methods
– numerical grades (1,2,3 etc)
– low, intermediate, high
– degree of differentiation (squamous cell carcinoma)
