Exam 3 (Lecture 19) - Neoplasia 3

Question 1

What is a transformation event?

Answer 1

Once cell has a change in DNA; gives rise to other cells that have errors.

Question 2

What are the three early signs of neoplasia?

Answer 2

1) Loosening of intercellular junctions
- Rounded cells
- Disorganized layers

2) Degradation of basement membrane
- Hard to confirm by light microscopy
- Described as “in situ”

3) Migration through basement membrane
- Possible to see if more than one cell

Question 3

What are “general rules” for metastasis?

Answer 3

• Not all malignant neoplasms metastasize
  
  • more locally invasive
• Some metastasize very early
  - hemangiosarcoma
• Some metastasize very late
  - squamous cell carcinoma

*These generalizations are true assuming all tumors “read the book” but they don’t.

Question 4

Describe the pathogenesis of hematogenous spread.

Answer 4

Clonal expansion, growth, diversification, angiogenesis > metastatic subclone > adhesion to and invasion of basement membrane > passage through extracellular matrix > intravasation > interaction with lymphoid cells > tumor cell embolus
- metastatic group survives
- only ones with the “right” genetic defects
can survive elsewhere

> adhesion to basement membrane > extravasation > metastatic deposit > angiogenesis > growth

Question 5

Describe the distribution of metastatic sites.

Answer 5

Favored sites:
- Hematongenous routes (lung/liver; vast blood supply)

  - Lymphatic spread (lymph node)

Not so favored sites:
- Skin
- Skeletal muscle
- Spleen +/- (depends on the specimen; round cell tumors do well
here)

Question 6

Why are lung, liver, and lymph nodes the organs most commonly affected by metastatic cells?

Answer 6

1) First capillary bed: filtration

2) “Fertile soil” adhesion
- certain cells survive well outside of normal tissues and some
don’t

Question 7

What is implantation metastasis?

Answer 7

• Transcoelomic metastasis
• “Seeding” of body cavity
• Mesothelioma

Transitional cell carcinoma:
- Spread by surgical instruments in the incision.

Question 8

What supports tumor production?

Answer 8

1) Growth factors

2) Inflammatory mediators

3) Proteases

4) Tumor antigens

Question 9

What is the stromal response with regard to inflammatory cells?

Answer 9

1) Migration toward tumor

2) Release of inflammatory mediators

3) Immune response to tumor

Question 10

What is the stromal response with regard to stromal fibroblasts?

Answer 10

1) Production of growth factors

2) Capsule formation

3) Desmoplasia

4) Myofibroblast development

5)Development of tumor-specific characteristics

Question 11

What is the stromal response with regard to the ECM?

Answer 11

1) Release of growth factors

2) Loss of structural integrity

Question 12

What is the stromal response with regard to vascular epithelium?

Answer 12

1) Angiogenesis

2) Altered permeability

3) Production of growth factors

Question 13

What are the differences between normal capillaries and tumor capillaries?

Answer 13

Normal Capillaries:
- Mature network
- Stable
- Structure and function of wall and network appropriate to
location in which they’re found

Tumor Capillaries:
- Evolving network
- Unstable
- Abnormal structure
- Abnormal function
- Inappropriate to the location

Question 14

What are the stimulators of tumor angiogenesis?

Answer 14

Stimulators (angiogenic substances):
- Vascular Endothelial Growth Factor (VEGF)
- basic Fibroblastic Growth Factor (bFGF)

Question 15

What are the inhibitors of tumor angiogenesis?

Answer 15

Inhibitors (angiostatic factors):
- Angiostatin
- Endostatin
- Vasculostatin

*These are typically drug interventions

Question 16

What are the characteristics acquired by malignant cells?

Answer 16

1) Loss of growth controls
- Loss of: contact inhibition, anchorage dependence (loss of
neighboring cells)

  - Cell cycle check points are abnormal. 

2) Antigen changes
- Different surface antigens (seen with immunohistocheimistry);
immune system may not recognize it

  - Malignant cells - hypoimunogenic (loss of differentiation)

Question 17

Describe pathogenesis of neoplasia.

Answer 17

Neoplasia is a disease of the genome.
- Multiple mutations, progressive changes

Mutations occur in genes that:
- Promote, suppress, and control cell growth and behavior (cell
cycle)
- Growth and differentiation

Question 18

What is the role of apoptosis? What happens to this process during tumor growth?

Answer 18

Genetically injured cells should undergo apoptosis
- p53 = guardian of genome; its job is to induce apoptosis or
delay cell cycle to allow DNA repair

Abnormal genes controlling apoptosis can allow genetically altered or injured cells to survive.
- Common mutation in >50% of human tumors

Question 19

What is p53?

Answer 19

Tumor suppressor gene.

Gate-keeping role

Loss of p53 allows for proliferation of genetically damaged cells