Understand the invasion-metastasis cascade Concept of tumor grade Concept of tumor stage

1. Staging, Grading and Spread
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2. Specific learning objectives
• Understand the invasion-metastasis cascade
• Concept of tumor grade
• Concept of tumor stage
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3. Spread
MetastasisInvasion
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4. Cascade
• invasion of ECM
• vascular dissemination
and homing of tumor
cells
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5. Invasion of ECM
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6. 1. loosening of tumor cells
Cadherin
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7. 2. Degradation of the basement
membrane and interstitial connective
tissue
Metalloproteinase
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8. 3. Changes in attachment
of tumor cells to ECM proteins
Receptor
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9. 4. Locomotion
Chemotaxis
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10. Vascular dissemination and homing of
tumor cells
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11. Organ predilection ?
• location of the primary tumor and its vascular or
lymphatic drainage
• organ that presents the first capillary bed they
encounter after entering the circulation
• Natural pathways of drainage do not readily
explain the distribution of metastases !
• Adhesion molecules – ligands
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12. Molecular signature
• EMT - epithelial-to-mesenchymal transition
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13. Grading / Staging
• quantify the probable clinical aggressiveness
of a given neoplasm (grading) and
• its apparent extent and spread (stage) in the
individual patient
• Why is it needed ?
• Make an accurate prognosis and for
comparing end results of various treatment
protocols
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14. Grading
• estimate aggressiveness based on
– cytologic differentiation of tumor
cells
– Number of mitoses within the
tumor.
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15. Staging
• based on
– the size of primary tumor
– spread to regional lymph nodes
– presence or absence of metastases
• TNM stage
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16. Take home points
• Invasion – hallmark of malignancy
• 4 steps of invasion
• Metastatic site depends on location /
chemokines
• Grading – cytologic appearance
• Staging – TNM – more value than grading
clincially
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17. Thank you
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