L15: Neoplasia 2 Flashcards
Define invasion?
Breach of the basement membrane with progressive infiltration and destruction of the surrounding tissue
Define metastasis?
Spread of tumour to a site that is physically discontinuous from the primary tumour
Unequivocally marks a tumour as malignant
Describe the multi-step journey required to colonise a secondary site?
- Grow and invade the primary site
- Enter a transport system and lodge at a secondary site
- Grow at a secondary site (colonisation)
At all points it has to evade destruction by immune cells
Process is inefficient
What needs to happen to a carcinoma cell for it to invade a new site?
Requires altered adhesion
Stromal proteolysis
Motility
What is the phenotype of these new carcinoma cells?
More like a mesenchymal cell (more unspecialised)
Epithelial to mesenchymal transition
What happens to the cells during altered adhesion?
Reduction in E cadherin –> loose adhesion between the cells
Changes to intergrin expression –> keep it attached to BM
What is meant by stromal proteolysis?
Degradation of the basement membrane and stroma
Happens through altered expression of proteases, matrix metalloproteinases (MMPs)
Take advantage of nearby non-neoplastic cells which provide growth factors and proteases –> niche
What allows the cells to move?
Changes to the actin cytoskeleton
Signalling through integrins is important and occurs via small G proteins–> Rho family
How do malignant cells travel to distant sites?
Blood vessels via capillaries and venules
Lymphatics
Fluid in body cavities –> pleura, peritoneal, pericardial and brain ventricles–> transcoelomic spread
What has to happen at the secondary site for the formation of a clinical metastasis?
Colonisation–> growth of the cells
Why do most metastasis fail to develop?
Unable to colonise
Lodge a secondary site forming undetectable cell clusters
Die or fail to grow into detectable tumour
What are metastasis that manage to survive but fail to grow called?
Micrometastases
Can habour many micrometastases and be disease-free–> called tumour dormancy
Why do apparently cured malignant neoplasms relapse?
Thought to be due to one or more micrometastases that start to grow
What determines the site of a secondary tumour?
1) The regional drainage of blood, lymph or coelomic fluid
- -> Blood-borne metastases–> next capillary bed (not always)
- -> Lymph–> lymph node
- -> Transcoelomic spread–> other areas in coelomic space or to adjacent organs
2) ‘Soil and seed’ phenomenon
- -> interactions between malignant cells and the local tumour environment at the secondary site
- -> ?Explains the unpredictable distribution of blood-borne metastases
What is the difference in spread between carcinomas and sacromas?
Carcinomas (epithelial) –> lymphatics
Sarcomas (stromal) –> blood stream
What are the common sites for blood-borne metastasis
Lung, bone, liver and brain
Which neoplasms commonly spread to bone?
Breast, bronchus, kidney, thyroid and prostate
Majority–> osteolytic lesions–> destruction of bone tissue
Prostate–> osteosclerotic lesion–> increased bone production, disorganised abnormal bone
What do we mean by personalities of malignant tumours?
Some neoplasms are very aggressive and metastasise early on, some almost never metastasise
Small carcinoma of bronchus–> aggressive–> widespread systemic metastases or locally advanced
Basal cell carcinoma–> rarely
Likelihood related to size of primary neoplasm
What do we mean by evasion of the host defence?
Tumour cells recognised by immune system as non-self and destroyed
Mediated by predominantly cell mediated mechanisms
Tumour antigens on MHC –> CD8+ cytotoxic T cells recognise
Immunosupressed patient»_space;cancer risk
Immunocompetent patients–> tumours can avoid the immune system–> via several mechanisms
In immunocompetent patients how do tumour cells avoid the immune system?
Loss or reduced expression of histocompatibility antigens
Expression of certain factors that suppress the immune system
Failure to produce tumour antigen
What is the concept behind immunotherapy agents?
Drugs optimise immune system
Immune system can help clear cancers
What are the classes of effects that neoplasms can have on the host?
Direct local effects –> due to primary or secondary neoplasm
Indirect systemic effect–> increasing tumour burden, secreted hormones and/or miscellaneous effects –> paraneoplastic syndrome
Benign tumours–> local effects from primary and hormonal effect most relevant
What are the local effect of neoplasms?
- Direct invasion and destruction of normal tissue
- Ulceration at a surface leading to bleeding
- Compression of adjacent structures
- Blocking tubes and orifices
- Raised pressure due to tumour growth or swelling (brain)
What are the systemic effects of neoplasia?
Increasing tumour burden–> parasitic effect on host
Secreted factors such as cytokines:
–> Reduce appetite and weight loss (cachexia)
–> Malaise
–> Immunosuppression (can be due to direct bone marrow destruction)
–> Thrombosis
Production of hormones
–> Usually benign tumours that are well differentiated
