Cancer – Evidence of malignancy

Objective

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

Tumor markers are substances, often proteins, that are produced by both normal and cancerous cells but are found at higher levels in cancer patients. They are used for various purposes in cancer diagnosis and management.

Common Tumor Markers

1. Prostate-Specific Antigen (PSA): Used for prostate cancer detection and monitoring.
2. CA-125: An indicator for ovarian cancer.
3. CEA (Carcinoembryonic Antigen): Associated with colorectal and other gastrointestinal cancers.
4. AFP (Alpha-Fetoprotein): Elevated in cases of liver cancer.
5. HER2/neu: An important marker in breast cancer.

Etio-pathogenesis of cancer

Cancer is a complex disease with multifaceted causes. The etio-pathogenesis of cancer involves both the study of its origins (etiology) and the cellular mechanisms leading to its development (pathogenesis).

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

FAQs

FAQs about Categorizing the Evidence of Malignancy

Q1: What is clinical evidence of malignancy? Clinical evidence of malignancy includes signs and symptoms that healthcare professionals observe in patients, such as unexplained weight loss, fatigue, pain, or unusual changes in bodily functions.

Q2: What is pathological evidence of malignancy? Pathological evidence involves the examination of tissue samples, revealing characteristics like abnormal cell growth, anaplasia (loss of cell differentiation), and histological findings, which describe the cellular structure.

FAQs about Tumor Markers

Q3: What are tumor markers used for? Tumor markers are substances that can be found at elevated levels in cancer patients. They are used for cancer diagnosis, monitoring treatment progress, and assessing the risk of recurrence.

Q4: Are tumor markers specific to a particular type of cancer? Some tumor markers are associated with specific cancer types. For example, PSA is primarily used for prostate cancer, while CA-125 is linked to ovarian cancer.

FAQs about the Etio-Pathogenesis of Cancer

Q5: What are the main genetic factors in cancer etiology? Genetic factors include inherited mutations that can increase susceptibility to cancer. These mutations can be passed down through families.

Q6: How do lifestyle factors contribute to cancer development? Poor diet, lack of physical activity, and obesity can influence cancer risk by promoting inflammation and DNA damage in the body.

FAQs about Various Types of Carcinogens

Q7: What are common chemical carcinogens? Common chemical carcinogens include tobacco smoke, industrial chemicals, and air pollutants. They can damage DNA, potentially leading to cancer.

Q8: How do physical carcinogens, like UV rays, contribute to cancer? Physical carcinogens, such as UV radiation from the sun, can directly damage DNA, increasing the risk of skin cancer and other malignancies.

Q9: Which viruses are considered biological carcinogens? Biological carcinogens include viruses like HPV, which is linked to cervical cancer, and hepatitis B and C, which are associated with liver cancer. These viruses can integrate their genetic material into host DNA, increasing cancer risk.