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

Cancer - Evidence of malignancy



       Evidence of malignancy


       Pathogenesis of cancer


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 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


       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


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


       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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