Lecture 15 - Neoplasia 2 Flashcards
What is the definition of Invasion?
Breach of the basement membrane with progressive infiltration and destruction of the surrounding tissues
What is Metastasis?
Spread of tumour to sites that are physically discontinuous from the primary tumour
What type of tumours can invade basement membranes?
Malignant tumours
What are the basic steps to metastasis?
Grow and invade at primary site (Initiation, promotion and progression)
Enter a transport system and lodge at a secondary
Grow at the secondary site to form a new tumour
What 3 key events happen in invasion involving a carcinoma cell?
Altered adhesion
Stromal proteolysis
Motility
What is epithelial to mesenchymal transition?
When the invading carcinoma cell takes on phenotype more similar a to the mesenchymal/stromal cells around it
What happens in the adhesion stage of invasion?
Reduced E-cadherin expression
Changes in Integrin expression
What are E-Cadherins?
Cell to cell adhesions
What are integrins?
Cell to basement membrane adhesions
What is the function of the Adhesion stage of invasion?
Frees carcinoma cells so they can move and invade the basement membrane
What happens in the stromal proteolysis stage of invasion?
Proteases released which degrade the basement membrane and stroma allowing for invasion
What happens in the Motility stage of Invasion?
Changes in the actin cytoskeleton of the carcinoma cell allowing it to move and invade
How do malignant cells take advantage of nearby non neoplastic cells?
Stimulate the stroma to produce growth factors and proteases
How do malignant cells spread to distant cells?
Blood vessels (Haematogenous spread)
Lymphatic vessels
Fluid in body cavities (transcoelomic spread)
How do malignant cells normally access nutrient?
Invade blood vessels
Create their own blood vessels
What is failed colonisation?
When a metastasis fails to establish and grow
How can dormant malignant cells occur?
Malignant cells lodge at secondary sites as tiny undetectable cell clusters that fail to grow
Why is cancer patient normally referred to as being in remission rather than being cured?
Dormant malignant cancer cells may be present and may be waiting for a optimal site to proliferate
What determines the site of a secondary tumour?
Where it drains in the blood, lymph or coelomic fluid
Where do lymphatic metastasis normallly go to?
Draining to lymph nodes
What lymph nodes do breast cancers go to?
Ipsilateral Axillary lymph nodes
Where do secondary tumours go which travel by transcoelemic spread?
Other areas in the coeclemic space or to adjacent organs
Where do blood borne metastasis end up forming secondary tumours?
Next capillary bed they encounter
How do carcinomas tend to spread first?
Lymphatics
How do Sarcomas normally spread?
Via bloodstream
What are some common sites of blood borne metastasis?
Lung
Bone
Liver
Brain
What is meant by nearly all bone tumours are metastases?
They are never normally the primary site of a malignant neoplasm
How are bone metastasis normally spread?
Haematogenous spread
What is a major symptom of metastatic bone disease?
Pain if symptomatic
What are the MAJOR neoplasm that metastasises to bone?
Breast
Prostate
Bronchus
Kidney
Thyroid
What affect does prostate cancer that has metastasised to bone have on the bone?
Ostesclerotic
Increased production of disorganised abnormal bone
What molecules present tumour antigens to immune cells?
What immune cells do they get presented to?
MHC Class I molecules
CD8+ cytotoxic T cells
What type of immune response is stimulated by exposing a CD8+ cell to a naive T cell?
Cell mediated immunity
Cytotoxic T cell response
How can tumours go undetected in immunocompromised patients?
Reduced expression of MHC molecules
Factors produced by pathogen which suppresses the immune system
Cant produce pathogen antigen
What are the direct local effects of neoplasms on a patient?
Direct invasion and destruction of normal tissue
Ulceration at a surface causing bleeding
Compression of adjacent strucutres
Blocking tubes and orifices
Raised pressure due to tumour growth/swelling (brain)
What are some systemic effects of neoplasia?
Increasing tumour burden (weight loss and fatigue)
Inappropriate hormone production
What is Cachexia?
Weight loss, fatigue, loss of muscle mass often associated with cancers
What type of tumours usually produce hormones?
Benign tumours
Why are you more likely to develop thrombosis with neoplasia?
Cytokines are produced
What is meant by Paraneopalstic syndrome
When patients with cancer develop signs and symptoms that cant be readily explained by the anatomical distribution of the Tumor or by the production of hormones from the tissue int which the tumour arose
What type of cancer is Hypercalcaemia common with?
Lung cancer
How can Hypercalcaemia occur with cancer? (Paraneoplastic syndrome)
Osteolysis - Caused by cancer due to either primary neoplasm or secondary metastases
Production for calcaemic humoral substances
What is Syndrome of Inappropriate ADH secretion?
Common with small cell lung cancer
Hyponatraemia common with it
What Miscellaneous systemic affects can neoplasia have on the body?
Fever
Hypoglycaemia
Skin problems (pruritus and abnormal pigmentation)
Neuropathies
Myositis
Clubbing
