Carcinogenesis , invasion & metastasis pathology medicine medical pathology cancer initiation

1. Carcinogenesis , Invasion
& Metastasis
Kanishka de Silva MS FRCS
Consultant Oncological Surgeon
Teaching Hospital Kandy

2. • Even in the absence of the original stimulus which
provoked it
• Invades the surroundings and metastasise regionally &
distally becoming a systemic disease.
What is Malignancy ( Cancer) ?
Monoclonal cell line that :
- grows independently
- uncontrollably
- in an uncoordinated manner
- at the expense of the normal tissues.

3. Carcinogenesis
Process of conversion of normal cells
into malignant cells .
Result of a disturbance in :
- control of cell proliferation
- cell differentiation
- relationship of cells to each other and to their surrounding

4. • Cells of the body :
differentiated cells & stem cells
• Cancer occur in :
stem cells (rather than dedifferentiated mature cells)
• Cancer treatment :
must be aimed at eradication of malignant stem
cells.
Normal stem cells replace the ageing cell
Malignant stem cells undifferentiated cell mass.
Cells with carcinogenic potential

5. Proto-oncogene
(Accelerator)
Gene products Cell division,
GF , GFR, 2nd Mes Prot, Differentiation
DNA binding proteins Ageing &
Death
Tumour Sup. gene
( Breaks )
Genetic basis of carcinogenesis

6. Carcinogens
Proto-oncogene Over expression , Point mutation Oncogene
Fusion
Tumour suppressor Mutation , Deletion Lost

7. Anti-cancer mechanisms of our
body
DNA repair mechanisms -------------- bio-engineers
Immune system ------------------------- police
• Multiple cancers could occur in rare, autosomal recessively
inherited diseases where there is an inability to repair
damaged DNA (Xeroderma pigmentosum, Bloom’s
syndrome, ataxia telangiectasia etc. ), & immune deficiency
states (inherited and acquired).

8. Mechanism of Invasion and
Metastasis
Invasion and metastasis is a multi-stepped process :
• Angiogenesis - Tumour acquires an additional blood supply
• Homotypic cell adhesion lost -
Normal cell adhesion is due to desmosomes, negative cell surface
charge and calcium dependent adhesion molecules – cadherins.
• Adhesion of tumour cells to the BM & extracellular matrices –
Mediated by a receptor-ligand mechanism known as laminin & integrin.
• Proteolysis -
Cells penetrate through the basement membrane and extracellular matrix
• Cells move through the connective tissue matrix and invade natural
anatomic pathways of spread such as lymphatics, blood vessels and serosa-
lined cavities.

9. Sites of high metastatic
predilection
• Liver
• Lungs
• Bones

10. Asymptomatic symbiotic
cancer carriers
Many cancers and pre-malignant forms go unnoticed for many years :
- 10-20% of normal men over 45 years have latent prostate cancers
- Screen detected malignancies may not surface for years
- Breast cancer deposits may occur even 20 - 30 yrs after treatment.
Therefore it is apparent that many people may be unaffected by overt
cancers throughout their lifetime, all the time having subclinical disease which
was never detected.
Thus it could be said that these people were in an
asymptomatic symbiosis with their cancers.

11. Cancer as a chronic ailment
• Better to consider cancer as a chronic
illness rather than a death warrant as there
may be quite a number of asymptomatic
symbiotic cancer carriers in our society.
• This concept would help to shed some
stigma attached with cancers as the sufferer
would now be considered as a person with
a chronic life long disease rather than a
necessarily fatal illness.

12. Do we need a cure ? What is
our goal ?
• In cancer treatment, thus cure constitutes
a questionable entity.
• What is important is quality of life.
• If this has been achieved whether we
have obtained a cure or an
asymptomatic symbiosis may not matter
as far as that person is concerned.

13. Thank You