Neoplasia

Question 1

Describe and explain the pathogenesis of cancer

Answer 1

cancer is a disease of the genome, arising from DNA alterations that dysregulate gene structure or function. DNA alterations can be caused by genetic injury or epigenetic mechanisms

Inherent error rate in DNA replication

Leads to uncontrolled purposeless cell proliferation that continues without the inciting cause

Epigenetic mechanisms
DNA methylation 
Histone acetylation 
MicroRNA expression
Epigenetic mechanisms are reversible, heritable alterations of gene expression that dont cause mutations in the genome

Question 2

Onocgenes and Tumour suppressor genes

Answer 2

HER-2/neu encodes for a cell surface receptor that can stimulate cell division
RAS the ras gene products are involved in the kinase signalling pathways
MYC transcription factor
SRC
hTERT (codes for telomerase)

p53 a transcription factor that regulates cell division and cell death
Rb alters the activity of transcription factors and therefore controls cell division
APC controls the availability of a transcription factor

Question 3

Initiation
Promotion
Progression

Answer 3

The introduction of a irreversible genetic change into cells by the action of mutagenic initiator. Initiated cells appear normal morphologically and may remain quiescent for years. The mutations give them a growth advantage so they respond more quickly/vigorously to mitogenic signals or are resistant to apoptosis inducing stimuli

Promotion
Initiated cells exposed to certain stimuli which alter gene expression and create an environment which drives proliferation. Initiated cells grow more rapidly and in less controlled way than normal cells. Promotors are non-mutagenic so are reversible.

Progression
Includes conversion of a benign tumour to an increasingly malignant one, Malignant conversion is irreversible. Complex poorly understood process, selecting for increasingly malignant clones that can then metastasize

Question 4

Hall marks of cancer

Answer 4

evading apoptosis
self sufficiency in growth signals
insensitivity to anti growth signals
sustained angiogenesis
tissue invasion and metastasis
limitless replicative potential

Question 5

Ki67

Answer 5

Growth fraction

the relative number of cells actively involved in cell cycle growth at that point in time

nuclear protein IHC staining
expressed in all active phases of cell cycle

Question 6

AgNOR

Answer 6

Growth time rate of cell proliferation or cell doubling time

silver staining

areas associated with RNA transcription

Question 7

KIT c-KIT

Answer 7

KIT is the protein aka a receptor found on the surface of mast cells. Ligand is a stem cell factor, activation via binding promotes cell survival, proliferation and differentiation.

c-KIT is the gene which encodes for the KIT receptor
mutations of the c-KIT gene can be detected by PCR two commonly tested mutations are exon 8 and exon 11

Different staining patterns
staining pattern 1 is normal membrane associated staining
staining II and III are focal or cytoplasmic and associated with lower survival times