Molecular Features Underlying Grading Criteria

Question 1

Tumor features used to assess grade

9

Answer 1

1. degree of differentiation
2. mitotic index (#/10 hpf)
3. degree of cellular or nuclear pleomorphism
4. amount of necrosis
5. invasiveness
6. stromal reaction
7. nucleolar size and number
8. overall cellularity
9. lymphoid response

Question 2

Molecular Mechanisms Underlying:

Mitotic Index

Answer 2

1. cyclins
2. cyclin-dependent kinases (CDKs)
3. prolifeating cellnuclear antigen (PCNA)
4. Ki67
5. bromodeoxyurindine (BrdUrd)
6. labeling index (LI)/growth fraction (GF)

Question 3

Molecular Mechanisms Underlying:

Percent necrosis

Answer 3

1. inflammatory mediators, including prostaglandins
2. cytokines (ILs, TNF-a)
3. Microvessel density (MVD)

Question 4

Molecular Mechanisms Underlying:

Invasiveness

Answer 4

1. MMPs
2. CAMs
3. plasminogen activators (PA)
4. integrin expression

Question 5

Molecular Mechanisms Underlying:

Stromal reaction

Answer 5

1. TGF-b
2. PDGF
3. bFGF
4. VEFGF
5. MVD mediators

Question 6

Molecular Mechanisms Underlying:

Nucleolar size

Answer 6

1. RNA transcriptional activity

2. AgNORs (sliver staining nucleolar organizing regions)

Question 7

Molecular Mechanisms Underlying:

Overall cellularity

Answer 7

1. Growth fraction
2. apoptosis factors (FasL, caspases, others)
3. Tumor doubling time

Question 8

Molecular Mechanisms Underlying:

Inflammatory (lymphoid) response

Answer 8

1. TNF-a
2. IFN-g (gamma)
3. increased MHCII
4. IL-2
5. ICAM (intercellular adhesion molecules)