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