1. Cancer: Metastasis By Joshua Bower and Asfand Baig Peer Support 2013/2014

2. Define metastasis Ability of malignant cells to invade and spread to distant (non-contiguous) sites

3. Distinguish between a primary and secondary tumour Primary - site where the malignant neoplasm arises Secondary - the site where the initial neoplasm has metastasised to

4. By what routes do cancers spread? [4] Locally Haematogenously (in the blood) Via lymphatics Transcoelomically (across a cavity; peritoneum or pleura)

5. Where do tumours of lymph node cells sit? In the subcapsular sinus - a region with few lymphocytes, thus permitting free lymph flow

6. List FOUR common sites for cancer metastasis [4] Brain Bone Lung Liver

7. Give THREE examples of primary tumours which commonly metastasise Prostate Breast Lung Problem based learning! PBL

8. A patient with known prostate cancer presents with paralysis of his legs. What is your diagnosis? Spinal cord compression Cancer cells have metastasised to the spinal cord and the tumour is compressing the nerves The prostatic venous plexus connects with vertebral veins, which is why it commonly spreads to the spinal cord

9. Describe the 8 steps of metastasis BLACK - Basement membrane invasion EXCLAIMED - Passage through Extra Cellular Matrix “I’M - Intravasation INSIDE - Immune interaction POTTER” - Platelet adhesion AFTER - Adhesion to endothelium ESCAPING - Extravasation AZKABAN - Angiogenesis

10. The Shawshank 8 (1 BM invasion) – he picks through the wall (2 ECM passage) – the room gets filled with water (3 intravasation) – he breaks into the sewer (4 immune interaction) – the sewer is filled with poo (5 platelet adhesion) – the poo is sticky (6 adhesion to endothelium) – he adheres to the sewer using poo (7 extravasation) – he breaks out of the sewer (8 angiogenesis) – his new life!

12. Slightly more detail… + BLACK - Basement membrane invasion - MMP (matrix metalloproteinase) stimulation + Exclaimed - Passage through Extra Cellular Matrix - MMP- + 'im - Intravasation - MMP stimulation and altered integrins + Inside - Immune interaction - decreased MHC class I expression + Potter' - Platelet adhesion - GF release (helps it travel around) + AFTER - Adhesion to endothelium - CD44 expression + ESCAPING - Extravasation - intergin expression and MMP stimulation + AZKABAN - Angiogenesis - VEGF, and other angiogenic GFs

13. Give TWO factors which can help cells spread [2] Increased motility (reduced integrin expression reduces the contact between cell and stroma; reduced cadherin expression allows cells to move apart) Altered synthesis of enzymes that breakdown the basement membrane and stroma (matrix metalloproteinases, MMPs)

14. What are the THREE classes of matrix metalloproteinases? Collagenases (degrade collagen I-III) Gelatinases (degrade collagen IV and gelatin) Stromelysins (degrade collagen IV and proteoglycans)

15. What acts to counterbalance MMPs? Tissue inhibitors of metalloproteinases (TIMPs) The balance of MMP:TIMP is important, and is a potential source of therapy

16. Give THREE reasons why all malignant cells don’t metastasise [3] Distant site environment may be inappropriate for growth of malignant cells Incorrect receptors Metabolic factors Failure of angiogenesis

17. Give THREE mechanisms by which angiogenesis can occur [3] Tumour-induced stimulation of angiogenesis (malignant cells could release angiogenic factors e.g. VEGF) Vasculogenic mimicry (tumour cells use their plasticity to express an endothelial phenotype to link up to the existing vascular system) Vessel co-option (invade into surrounding vessels, with death of lining endothelial cells leading to tumour cells lining vascular spaces)

18. Give an example of an anti- angiogenic factor Angiostatin Endostatin Vasostatin Thrombospondin

19. List FOUR factors which determine the effect a tumour will have [4] Site of tumour Extent of local spread Site of metastasis Extent of metastatic spread Functional effects Paraneoplastic effects

20. Give an example of a paraneoplastic effect Dermatomyositis (autoimmune attack of skin and muscle as a reaction to a tumour) Cachexia Anaemia Clubbing

21. You have a patient with small cell carcinoma of the lung. What treatment option are you unlikely to carry out? Surgery - because by the time of diagnosis, it has almost universally metastasised

22. Name THREE common sites for metastatic spread in the thorax Lung Pleura Mediastinal lymph nodes

23. What is in situ malignancy? An epithelial neoplasm with features of malignancy, but with no basement membrane invasion

24. A patient with carcinoid tumour of the jejunum with liver and bony mets presents with flushing, diarrhoea and wheezing. What is your diagnosis? Carcinoid syndrome - severe liver mets result in the failure of adequate serotonin metabolism

25. Give FOUR local effects of malignant neoplasias [4] Destruction of surrounding tissue Obstruction or constriction of a hollow viscus Ulceration Infiltration into NAVL Space-occupying lesions (eg in the brain)