BIOLOGY OF CANCER

Maha Al Omari

OBJECTIVES
At the end of the lectures the student should be able to identify and explain: Cell Proliferation and Differentiation

Benign and Malignant Neoplasms

Etiology of Cancer Molecular Basis of Cancer, Host and environmental factors (immunologic mechanisms, chemical carcinogens, radiation, oncogenic viruses)

TERMINOLOGY
Oncology: the study of tumors Neoplasia: new growth (indicates autonomy with a loss of response to growth controls)

A NEOPLASM is an abnormal mass of cells which:

Exhibits uncontrolled proliferation Persists in its growth after the stimulus which originally produced the growth has stopped
Cancer: refers to malignant tumor

TYPES OF NEOPLASMS
Benign: localized and amenable to surgical removal; rate of growth is relatively slow and growth occurs in an orderly pattern, patient usually survives

Malignant: : More rapid, disorderly growth, invasive tumor capable of destroying structures and spread to distant sites (metastasis); may result in early death of the patient

EXAMPLES OF BENIGN TUMORS

fibroma: benign tumor of fibrous tissue lipoma: benign tumor of fat adenoma: benign glandular tumor chondroma: benign cartilaginous tumor

EXAMPLES OF MALIGNANT TUMORS

Sarcoma (mesenchymal derivation: fibrosarcoma, chondrosarcoma) Carcinoma (epithelial derivation: adenocarcinoma, squamous cell carcinoma) lymphoma/leukemia Adenocarcinoma: malignant glandular tumor

Tumor Behavior
Benign Versus Malignant

The terms benign and malignant describe the biologic behavior of a tumor.
The biologic behavior is characterized by degree of differentiation of the tumor and by the rate of growth (and rate of cell death)

Benign
Expansile growth C often encapsulated C well demarcated

Malignant
Invasive growth C non-encapsulated C poorly circumscribed

No metastases
Slow growth rate Necrosis, hemorrhage, ulceration: not frequent No systemic symptoms

Metastases
May have rapid growth Necrosis, hemorrhage, ulceration:

frequent
Systemic symptoms present: cachexia, anemia, anorexia, etc.

Cell structure near normal

Abnormal shapes, larger cell and nucleus

Tissue structure :Orderly

Tissue structure: Disordered, irregular

Benign
Invasive growth: uncommon Few or no mitoses Anaplasia; Minimal

Malignant
Invasive growth: typical Increased number of mitoses Anaplasia: Typical

Prognosis: Good

Prognosis: Poor

DIFFERENTIATION
DIFFERENTIATION: Degree of morphologic and functional resemblance to comparable normal cell. Well-differentiated tumors contain cells that resemble the normal cells of origin Poorly-differentiated or undifferentiated tumors contain cells that do not resemble their normal counterparts (ancillary studies may be needed to determine the cell of origin)

Benign tumors are composed of well-differentiated cells. Malignant tumors are characterized by a wide range of cellular differentiation.
Anaplasia (cellular pleomorphism, hyperchromatic nuclei, high N:C ratio, giant cells, bizarre nuclei) is a feature of malignant tumors. - Is the pattern of change that reflects an earlier cell form
Anaplastic cell regained reproductive capacity at the expense of functional specialization. ANAPLASIA: Lack of differentiation, is a cancer marker.

ENCAPSULATION: Induction of peripheral fibrosis, characteristic of benign neoplasm

DYSPLASIA
Denotes a loss of architectural organization and a loss of cell uniformity in epithelium pleomorphism and mitoses are more prominent than in the normal usually graded: mild, moderate, severe, and carcinoma-in-situ mild to moderate dysplasia is potentially reversible

DYSPLASIA
Dysplasia is a non-neoplastic proliferation. Dysplasia may or may not progress to cancer.

Oncogenesis: Are those changes induced by oncogenic factors in the normal cellular behavior which lead to the development of malignant/ cancer behavior of cells.

TUMOR GROWTH RATE:

Generation time --- the time between successive cell divisions ( mitosis- cell rest- metabolic changes). Doubling time ---the time required to double the number of tumor cells or the size of the tumor

TUMOR INVASION
INVASION/INFILTRATION: Unrestricted permeation into contiguous structures, characteristic of malignant neoplasms. Benign tumors usually grow by slow expansion. Malignant tumors usually infiltrate and may destroy surrounding tissue (cell surface and the extracellular matrix play an important role).

TUMOR METASTASIS
METASTASES: Remote distant tumor implants from the primary neoplasm. indicates malignancy a discontinuous spread of the tumor Methods of metastasis include: (1)seeding of body cavities, (2) lymphatic spread, and (3) hematogenous spread.

GRADING AND STAGING

Grading is based on the microscopic features of the cells which compose a tumor and is specific for the tumor type. follow biopsy( grade I =highly differentiated cells , well ordered, few mitosis- grade IV= poorly differentiated , pleomorphic cells and increased mitosis) Staging is based on clinical, radiological, and surgical criteria, such as, tumor size, involvement of regional lymph nodes, and presence of metastases( TNM) Staging usually has prognostic value. T0 , 1, 2, 3 0 No tumor at primary site No Lymph node involved - No distant metastasis

MENINGIOMA

MELANOMA

ETIOLOGY ( CAUSES) OF CANCER

Cancer incidence vary with age, sex, race and geographic location. Hereditary traits have been observed, also variations in diet and exposure to chemical and physical agents in the external environment contribute to the development of neoplasia.
Etiologic Mechanisms:

Genetic factors Oncogenic viruses DNA -RNA chemical carcinogens physical carcinogens others

1.GENES AND CANCER

The formation of new tissue is based on the balance of new cell formation vs cell losses. When a cells DNA is damaged ,it may be repaired . If repair is impossible apoptosis eliminates the affected cells

If there is misregulation in the process of apoptosis, cells with damaged DNA that should be eliminated are retained. They can go to divide & so form an increasing pool of genetically unstable cells likely to undergo transformation into a tumor.

GENETIC FACTORS
Proto-oncogenes: genes that normally control cell division ( mitosis, DNA repair & apoptosis) e.g. bcl-2.
If proto-oncogenes are defective their abnormal proteins cant maintain the balanced regulation needed for normal tissue formation and are called now Oncogenes. Tumor suppressor genes: genes that prevent replication of cells that have become cancerous e.g. p53.

1. GENES AND CANCER

Oncogenes are implicates in many human tumors

Oncogenes that is unable to code for production of cell growth inhibition their lack means growth is unrestrained
If oncogenes produce excessive quantities of growth promoters , high rates of mitosis generate inappropriate tissue excess.

Heredity :

e. g. polyposis coli , xeroderma pigmentosa , retinoblastoma.there is familial pattern of inheritance. In some tumors such as breast cancer, ovarian and colon carcinoma heredity plays a role but this role is not well understood

2. ENVIRONMENTAL FACTORS A. CHEMICAL CARCINOGENS

Chemical carcinogens alter DNA by binding to it

The result is a change in the cells information pool that may give rise to formation of tumor. Some chemicals might activate a virus already present in the cell , or by interacting with DNA or other cell constituents. Some individuals have a higher risk of developing tumor due to variation in enzymes levels within population

CLASSES OF CHEMICAL CARCINOGENS INCLUDE:

1. aromatic amines: used as dyes fabrics or as coloring agents e.g. methylaminobenzene .. Liver carcinoma Naphthylamines urinary bladder carcinoma 2. Nitrosamines: people eating diets rich in amino acids containing proteins ( bacon , ham , sausage , canned meats ) are at risk. Nitrosamine form products that interfere with DNA replication and lead to neoplastic transformation. Nitrite ions ( commonly used as meat preservatives )+ amino acids in presence of heat and acidity lead to nitrosamine formation. 3. Aflatoxins: carcinogen of biological origin. Produced by fungi ( aspergillus species) it is a hepatocarcinogen Produced as a result of improper storage of peanuts, cotton seeds , corns.

CHEMICAL IRRITANTS

B. PHYSICAL CARCINOGENS

Energy in the form of solar or ionizing radiation can induce tumor formation. Both are known to damage the cells specially DNA. Radiation may activate other oncogenic factors or suppress antitumor defenses.

Sources of radiation 1.ultraviolet light( sun)

2. ionizing radiation( X ray) or radioactive materials in mining or medicine.

N.B. unnecessary exposure to medical or dental x ray should be avoided.

C. ONCOGENIC VIRUSES: VIRUSES INTERACT WITH CELLUAR CHROMOSOME

CONVERTING PROTOONCOGENES INTO ONCOGENES.
DNA VIRUS: Human papiloma virus (skin &cervical cancer) Herpes simplex typeII(cervical carcinoma) Epstein-barr (burkitt`s lymphoma & nasopharyngeal carcinoma) hepatitis B (hepatocellular carcinoma)

ONCOGENIC VIRUSES

RNA virus: Mainly reverse transcriptase viruses Cytomegalovirus (*Kaposis sarcoma) HTLV-I and II (T leukemia) *AIDS related tumors

D. IMMUNOLOGICAL FACTORS

infection

Congenital immune defects

Nutrients or Other deficiencies

Immune suppression

Immunedeficiency state

Loss of tumor antigens

Reduced antitumor effectiveness

Tumor growth

TAA: Tumor associated antigens are antigens on some normal cells also present on tumor cells. TSA: Tumor specific antigens are antigens that occur only on tumor cells. The immune system is supposed to be able to recognize these antigenically altered cells and destroy them immune surveillance IS on guard and ready to act.

There is higher tumor incidence in those with immune deficiency An infection, some nutritional deficiencies, and other factors might cause disturbance in normal immune response allowing tumors to evade recognition and destruction. Some tumors have immune suppression abilities which allows their survival.

Thank you