STEP / TOPIC
WHAT HAPPENS
KEY MOLECULES
CLINICAL LINK
Tumor cells lose their grip on each other.
↓ E-cadherin
Diffuse (signet-ring) gastric carcinoma; lobular breast carcinoma (single file)
2 · Breach basement membrane
Cells attach to the membrane and digest it.
Laminin receptors; MMPs (type IV collagenase)
The step that turns in situ into invasive
3 · Migrate through stroma
Cells crawl through extracellular matrix.
Integrins binding fibronectin; cytoskeletal motility
Desmoplastic (fibrous) stroma reaction
4 · Enter vessels & survive
Intravasation; tumor cells coat themselves with platelets and evade immune cells.
PD-L1 ↑, MHC I ↓
Checkpoint inhibitors (anti-PD-1, anti-CTLA-4)
Extravasate and grow where the "soil" suits them; recruit blood vessels.
Chemokine receptors (organ tropism); VEGF
Bevacizumab blocks VEGF
To regional nodes first.
Sentinel node = first draining node
Most carcinomas
Through veins to lung and liver, or arteries to bone and brain.
Sarcomas, plus carcinomas that invade veins
RCC (renal vein), HCC (hepatic vein), follicular thyroid, choriocarcinoma
Tumor cells shed into the peritoneum or pleura.
—
Ovarian carcinoma (omental caking); pseudomyxoma peritonei (appendix mucinous tumor)
Degree of differentiation on microscopy: well → moderately → poorly differentiated.
Architecture + nuclear features
Gleason score (prostate) is a grading system
TNM: T = size/depth, N = nodes, M = distant spread.
From imaging and surgical resection
Best prognostic factor; M is the single most important