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WHAT IS INVASION?
• The ability of cells to break through normal barriers (e.g. basement membrane), and then spread. • Into surrounding tissue• In lymphatic/vascular channelsMalignant cell = ability to invade basement membrane and metastasise
WHAT ARE CADHERINS AND INTEGRINS?
• Cadherins : glycoproteins between cells : maintain position and polarity
• Integrins : glycoproteins between cells and stroma : anchoring
• Malignant cells: reduced expression of integrins and cadherins : cells detach from each other and move
1) WHAT IS A MATRIX METALLOPROTEINASE? 2)NAME THREE FAMILIES OF MMPS.
3) WHAT COUNTERACT MMPS?
1) Enzymes which degrade extracellular matrix
2)
• Collagenases : degrade Collagen I-III
• Gelatinases : Collagen IV and gelatin
• Stromelysins : Collagen IV and proteoglycans
3) Tissue Inhibitors of Metalloproteinases (TIMPS)
WHAT IS METASTASIS? WHAT ARE THE FOUR ROUTES OF METASTASIS?
•Ability of malignant cells to invade into lymphatics, blood vessels and cavities, and spread to distant (non contiguous sites)
• Transcoelomic• Lymphatic• Blood stream• Surgical (post-transplant)
WHAT ARE THE COMMON SITES OF METASTATIC SPREAD (LYMPHATIC,
VASCULAR, TRANSCOELOMIC)
•Lymphatic : local and distal lymph nodes
•Vascular spread : lung, liver, bone and brain
•Transcoelomic spread : Ovary, stomach, breast, lung
WHAT ARE THE STEPS OF METASTASIS?
Invade BM Passage through ECM
Intravasation Immune interaction Platelet adhesion Adhesion to
endothelium Extravasation Angiogenesis
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NAME AS MANY HALLMARKS AS YOU CAN?
• What happens first:• Genome Instability• Deregulating cellular energetics
• How does it survive (and become ‘immortal’):• Self sustaining growth signals• Evade growth suppression• Limitless/endless replication• Avoid immune destruction• Resist cell death• Tumour promoting inflammation
• How does it thrive:• Invasion and metastasis• Angiogenesis
WHAT IS THE DIFFERENCE BETWEEN PRIMARY AND SECONDARY METASTASIS?
• Primary – site where the malignant neoplasm arises
• Secondary – metastasis e.g. carcinoma that has spread to another organ
WHICH ARE THE 3 CANCERS WITH THE HIGHEST MORTALITY RATES IN WOMEN?
1. Lung
2. Breasts
3. Bowel
WHICH ARE THE 3 CANCERS WITH THE HIGHEST MORTALITY RATES IN MEN?
1. Lung
2. Prostate
3. Bowel
What is the tumour staging system in breast cancer?
TMN staging system.T = the size of the TumourN = the Node involvementM = Metastases
T1 = <2cm size T2 = 2 - 5 cm T3 = skin and/ or chest wall involvedN0 = no axilliary nodes involvedN1 = mobile nodes involvedM0 = no metastasesM1 = demonstrable metastases
What is tumour grading?The grading is the degree of cellular differentiation based on histological appearance of the tumour.
e.g for breast cancer what are you looking for?
1. Degree of tubule formation2. Extent of nuclear variation3. Number of mitosis
Grades:
1 2 3
WHAT IS THE NAME OF THE PROGNOSTIC INDEX IN BREAST CANCER?
• Nottingham prognostic index:
• Size x 0.2
• Stage (1 – 3)
• Grade (1 – 3)Score 5-year survival
>/=2.0 to </=2.4 93%
>2.4 to </=3.4 85%
>3.4 to </=5.4 70%
>5.4 50%
