14. Neoplasia 2 Flashcards
What is the definition of invasion?
Breach of the basement membrane with the progressive infiltration and destruction of the surrounding tissues
What is a metastasis?
Spread of tumour to sites that are physically discontinuous from the primary tumour
Marks tumour as malignant
What is the multi step journey of a tumour?
Grow and invade primary site
Enter a transport system and lodge at a secondary site
Grow at the secondary site to form a new tumour (colonisation)
What does a cardinal cell need?
Invasion involves 3 key events: - altered adhesion - stromal proteolysis - motility Cell carries out epithelial to mesenchymal transition
What adhesion does a carcinoma cell need to metastasise?
Reduction in E-cadherin expression
Changes in integrins expression
What stromal proteolysis does a carcinoma cell need to metastasise?
Altered expressions of proteases, notably matrix metalloproteinases
Degrade basement membrane and stroma to allow for invasion
What niche is required for malignant cells?
Stroma
Fibroblasts
Endothelial cells
Inflammatory cells
How does a malignant cell become mobile?
Involves changes in the actin cytoskeleton
How do malignant cells spread to distant sites?
Blood vessels - usually veins
Lymphatic vessels
Fluid in body cavities - transcoelomic spread (pleura, peritoneum, pericardium)
What happens when malignant cells reach a secondary site?
Colonisation
Many fail colonisation due to unsuitable niche
Most malignant cells lodge at secondary sites as tiny clinically undetectable cell clusters that either die or fail to grow
Which cancers are prone to micro metastases?
Breast cancer
Melanoma
What determines the site of a secondary tumour?
Regional drainage of blood, lymph or coelomic fluid
- for lymphatic metastasis this is predictably to draining lymph nodes
- breast cancer goes to ipsilateral axillary lymph nodes
- for transcoelemic spread usually to other areas in coelemic space or to adjacent organs
- for blood borne metastasis sometimes next to capillary bed that malignant cells encounter
Where do carcinomas tend to spread first?
Via lymphatics
Where do sarcomas spread via?
Blood stream
Where are the common sites of blood borne metastasis?
Lung
Bone
Liver
Brain
What are the more common neoplasms that spread to the bone?
Breast Bronchus Kidney Thyroid Prostate
Describe the evasion of host defence
Tumour cells can be recognised by immune system as non-self and destroyed
Mediated predominantly by cell mediated mechanisms
Tumour antigens are presented on cell surface of major histocompatibility complex molecules recognised. By CD8+ cytotoxic T cells
How can tumours avoid the immune system in immunocompetent patients?
Loss or reduced expression of histocompatibility antigens
Expression of certain factors that suppresses the immune system
Failure to produce tumour antigen
What are the local effects 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?
Increased tumour burden results in a parasitic effect on the host
Together with secreted factor such as cytokines: reduced appetite and weight loss, malaise, immunosuppression, thrombosis
Production of hormones
