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

• P₅₃gene is mainly involved in the development of cancer

Cancer - Evidence of malignancy - B. Pharma 2nd Semester Pathophysiology notes pdf