Cancer Pathology, Genes, Immunosuppression HN24-36 VNs

Question 1

Histological Features of SCC (7) “KIDDIE- M”

Answer 1

1. Keratin pearls
2. Intercellular bridges
3. Disorganized growth
4. Dyskeratosis
5. Immature Cells (Lack of maturation)
6. Enlarged nuclei with prominent nucleoli
7. Mitotic figures (increased and atypical)

Question 2

6 Criteria for Poorly Differentiated SCC. (6) “MMMPIK”

Answer 2

Mitosis Abnormal
Mitosis Increased
Multinucleated Cells
Pleomorphism
Intercellular Bridges LOST
Keratin LOST

Question 3

Field Cancerization:

1) Definition
2) 2 Theories

Answer 3

1) Definition - premalignant changes and secondary tumours can be seen in area adjacent to the original tumour

2)
a) Independent Clone Theory - independent clones with unique genetic alterations

b) Common cellular clone - common cell with spread to adjacent regions

Question 4

5 Phases of the Cell Cycle.
Which is:
a) most sensitive
b) most resistance

Answer 4

G1 – 1st Growth phase in preparation for DNA synthesis
S – DNA Synthesis (late S - most resistant)
G2 – Cell Growth, duplication of cell proteins & structures
M – Mitosis (early M - most sensitive)
G0 – Resting phase

Question 5

Definition of Oncogene

5 Types according to Protein function “GGSPT” and one example each

Answer 5

Growth factor – int-2
Growth factor receptors – erbB/neu
Signal transducers for surface growth factor receptors – ras 
Protein kinases – b-raf, c-raf
Transcription regulator – myc

Question 6

HNSCC Genes:

1) 4 Tumour Suppressor Genes
2) 5 Oncogenes “BCCH ER”
3) 4 antagonistic relationships of genes (oncogene + tumour suppressor)

Answer 6

1. Tumour Suppressor:
   p16 + 21 (surrogate markers for HPV)
   p53 - HPV E6 loss (poor prognosis)
   pRB - HPV E7 loss

2. Oncogenes
Bcl-2 - counteractics p53
C-myc 
Cyclin D1
HER2/neu - tyrosine kinase
ErbB family tyrosine kinase - worse prognosis
RET - MEN2

3. Antagonistic Relationships (oncogene + tumour suppressor)
Bcl-2 + p53
Cyclin + P53
Cyclinp + p16/21 
TFE2F + pRB

Question 7

Gardasil Vaccine

1) Types (2) - subtypes covered for each
2) Dosing regimen for Peds vs Adults
3) % benefit of reducing HPV OPSCC

Answer 7

Types:

1. Gardasil - (Quadrivalent HVP 6,11,16,18)
2. Gardasil 9 – (9-valent - HPV 6, 11, 16, 18, 31, 33, 45, 52, 58)

Dosing Regimen
Peds = 2 injections over 6 months
Adults = 3 injections over 6 months

Vaccination:
Reduces incidence of HPV OPSCC by 30%

Question 8

3 Genetic Alterations of precancerous lesions to invasive laryngeal SCC

Answer 8

1) p16 mutation
2) loss of heterozygosity
3) Overexpression of Cyclin D1 (increased cell proliferation)
3) p53 alterations (abnormal repair)

Question 9

What is the Pathogenesis of HPV associated SCC? (3 points)

Answer 9

viral oncoproteins inactivate tumour suppressor genes for unregulated cell growth
E6 –> p53
E7 –> pRb

Question 10

What is the function of p53?

Answer 10

1) controls cell cycle
2) binds to cyclin dependent kinins
3) arrests cells replication at G1/S junction
4) induces apoptosis if DNA repair fails
5) activates DNA repair
6) Prevents angiogenesis

Chromosome 17p13