Cancer – Evidence of malignancy
Content
Cancer
• Evidence of malignancy
• Carcinogenesis
• Pathogenesis of cancer
Objectives
At the end of this lecture, student will be able to
• Categorize the evidence of malignancy
• List various tumor markers
• Discuss the etio-pathogenesis of cancer
• Describe
various types of carcinogen
Evidence of malignancy
A. Clinical evidence
q Age
of patient – cancer, a disease of adults
q Rate
of growth – rapid growth of tumor indicates malignancy
q Evidence
of infiltration – sign of malignancy
q Presence
of metastasis – distant metastasis
indicates cancer that is not operable
B. Macroscopic evidence
• Tumor
makes its appearance either as a mass or as an ulcer
• Size
& shape of different tumor are different
• Benign
tumor – Sharply marked from surrounding tissues, shows fibrous capsule all
around
• Malignant
tumor – poorly defied, capsule is missing
• Different
tumor may have different color
• Malignant
melanoma – jet black
• Renal
cell carcinoma – yellow
• Most
of the cancers are greyish white in color
C. Microscopic evidence
q Cytological
diagnosis :
• Discharges,
secretion, excretion and effusion in body cavities examined for the presence of
cancer cells
• Thin
smear of the materials are fixed, wet with ethyl alcohol and stained by special
techniques
• Aspiration
biopsy
• Tumor
mass is aspirated with a needle or syringe
• Cylinder
portion of tumor tissue is obtained
• Histological
sections are prepared
• If
fluid obtained – Smears are made for cytological diagnosis
• Incisional biopsy
• Portion
of tumor tissue removed surgically, examined histologically
• Excisional biopsy
• Whole
of small lesion excised along with a safe margin of healthy tissue
q Tumor
Marker
• Biochemical assays of products
elaborated by the tumour cells in blood or other body fluids
• Tumour markers include: cell surface
antigens (or oncofoetal antigens), cytoplasmic proteins, enzymes, hormones and
cancer antigens
Tumor
markers
Etio-pathogenesis
of cancer
CARCINOGENS
Carcinogens are categorized into 4 groups
• Chemical
carcinogens – includes chemicals and drugs
• Physical
carcinogens – includes radiations
• Hormonal
carcinogens
• Biological
carcinogens – Viruses
Chemical
carcinogenesis
Process of cellular transformation of chemical carcinogen
occurs in
2 stages – Initiation
of carcinogenesis
– Promotion
of carcinogenesis
q Initiation
of carcinogenesis
2 types of chemical carcinogens – directly acting &
indirectly acting
• Directly
acting (alkylating agents) – Does not require conversion to become
carcinogenic; Can induce cellular transformation
• Indirectly
acting/ Procarcinogens (aromatic
amines, azodyes)– require metabolic conversion to become active
Promotion
of carcinogenesis
• In
this stage, cells are selectively stimulated to proliferate by activation of growth
factor
• Promoters
of carcinogens – Phenols, Hormones, artificial sweeteners, drugs like
phenobarbitone
• Pro
carcinogenesis – when 2 carcinogens acting simultaneously to enhance the
effect
Physical
carcinogenesis
Radiation carcinogenesis
• Ionising
radiations & UV rays can cause cancer
• UV
rays – immune suppression &DNA damage
Eg. Squamous cell
carcinoma, basal cell carcinoma, malignant melanoma
• Ionising
radiations – X- rays, α–
rays, β– rays, radioactive
isotope, protons, neutrons
Eg. Blood cancer,
cancer of thyroid, skin, lungs, breast & salivary glands
Non radiation carcinogens
• Mechanical
injury as a result of gall bladder stones,
kidney stones, scars of bones & trauma
• Other
examples include glass and plastics
Hormonal
carcinogenesis
Organs or tissues which undergo proliferation under the
influence of hormones are likely to develop cancer
Examples:
• Estrogen
induced cancer – breast cancer, squamous cell carcinoma, carcinoma of
cervix, tumor of myometrium
• Contraceptive
steroids – oral contraceptives for long time can cause breast and liver
cancer
• Anabolic
steroids – increases risk of developing cancer
Biological
carcinogenesis
• Viruses
cause different type of cancer (oncogenic viruses)
• Parasites
cause cancer of urinary bladder
• Bacteria
– gastric lymphoma and carcinoma
Examples of viruses causing cancer
• Human
papilloma virus
• Epstein
barr virus
• Hepatitis
B virus
Pathogenesis
of cancer
• Basis
for tumor formation – change in genetic factors leading to non-lethal damage to
cells
• 2
genes involved during the development of cancer
– Growth
promoter proto oncogene
– Growth
supressor anti oncogene
• Most
well studied tumor suppressor gene – P53 gene
• P53,
critical gate keeper, prevent formation of cancer
• Localized
in nucleus, transcribe several gene when required
When DNA damage by irradiation, mutagenic chemical –
increase in
P53 gene – it binds to DNA – simulates its repair
2 major effects of P53 gene
• Cell
cycle arrest
• Apoptosis
ü Cell
cycle arrest in late G1 phase – prevent cell from entering into next cell cycle
ü Allows
time for DNA repair
ü If
damaged repaired – stimulates MDM2 gene, down regulates P53 gene
, relieve cell block
ü If
damaged not repaired – cell apoptosis
ü Inhibition
of P53 gene by its mutation may leads to cancer
Summary
• Malignancy
can be determined by evidences obtained by clinical, microscopical examination
of tumor
• Carcinogens
are the agents that causes cancer
• Cancinogens
can be physical, chemical, hormonal or biological
• Basis for tumor formation is change in genetic
factors leading to non-lethal damage to cells
• 2
genes involved during the development of cancer growth promoter proto oncogene
and growth suppressor anti oncogene
• P53
gene is mainly involved in the development of cancer
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