neoplasm 3 Flashcards
what are the 4 steps of invasion of ECM
1) Detachment
2) attachment to matrix component
3) degradation of ECM
4) Migration of tumor cells
describe the detachment of tumor cells
- tumor cells remain attached to each other by adhesion molecules (E-cadherins)
- In many malignant tumors, E-Cadherin is NOT produced
- Cohesiveness of tumor cells is reduced
describe the attachment to matrix component
- laminin/laminin receptor
- tumor cells have laminin receptors in order for it to attach to matrix
describe the degradation of ECM (penetration)
- tumor cells or fibroblasts/inflammatory cells release collagenases (MMP) to degrade type IV Basement membrane collegen
describe the migration of tumor cells
- binding of fibronetin/its receptor help migration
- tumor cell secreted motility factor plays a critical role in migration (locomotion)
define metastasis
- tumor implants discontinuous with primary tumor
what is the metastatic cascade
- ability to invade and metastasize
1) invasion of basement membrane
2) movement through extra-cellular matrix
3) vascular dissemination
4) homing
what are the factors involved in vascular dissemination
- NK cells kill many cells in circulation
- tumor cells are more protected in clumps and may clump with platelets
- must arrest and extravasate to set up viable metastasis
- Expression of CD44 on tumor cells seem to favor metastasis
what are the three routes of metastasis
- seeding of body cavities
- lymphatic spread
- hematogenous spread
describe seeding of body cavities
- malignant cells exfoliate and implant and invade tissue in a body cavity
describe lymphatic spread
- most common type of metastasis
- more typical in carcinomas rather than sarcomas
- -> lymphatics empty into blood vessels –> eventual spread is hematogenous
- pattern of nodal spread reflects normal lymph drainage
- -> e.g. lung Carcinoma –> bronchial nodes –> tracheal nodes
what carcinomas do NOT spread through lymphatics
- Follicular carcinoma (local invasion)
- renal cell carcinoma (blood)
- hepato-cellular carcinoma (blood)
describe hematogenous spread
- Typical sarcomas or in carcinomas that are in late stages
- arteries are more difficult for tumor to penetrate than veins (in venous invasion, blood-borne cells follow venous flow to other organs
- frequently occurs in liver and lungs
define sentinel lymph node
- 1st node in a regional lymphatic system that receives lymph flow from priamry tumor
- detected by radio labeled tracers or blue dyes
- used to detect spread of melanomas, breast cancer, colon cancer and other cancers
describe bone metastasis
- most common site for bony metastasis is vertebral column because of batson paravertebral venous plexus connects vena cava and vertebral bodies
- Pain is the most common symptom of bone metastasis (best relieved by local radiation therapy)
- 2 types:
- -> osteoblastic metastasis
- -> osteolytic metastasis
describe osteoblastic metastasis
- RADIO-DENSE loci noted on X-rays
- Increase serum alk phosphatase: indicate reactive bone formation
- e.g prostate cancer (most common type)
Describe osteolytic metastasis
- produce lucencies in bone on X ray - Pathologic fractures
- tumors produce factors that activate OSTEOCLASTS
- -> PGE2, Osteoclast activating factor (IL-1)
- potential for hypercalcemia in blood
- common cause is breast or colon cancer
describe the 4 grades of tumors
I) well differentiated
II) moderately differentiated
III) poorly differentiated
IV) nearly anaplastic
describe the TNM system of staging
T = size of primary tumor (T0-T4) N = nodal involvement (N0-N3) M = distant metastases ( M0 - M2)
what do the Dukes system grade
- colorectal cancers
what does the ann Arbor system grade
- for hodgkin and non Hodgkin lymphomas
what are the most common tumors in males
- prostate
- lung
- colorectal cancers
what are the most common tumors in females
- breast
- lung
- colon
- rectum
describe the geographic factors involved in gastric cancer and skin cancers
- gastric cancer = high incidence in japan
- skin cancer = more common in new zealand than in iceland
- -> due to race: persons with fair skin, light hair, and blue or green eyes are more likely
