Carcinogenesis, Cancer Diagnosis

Khalid Ali Alfaqih, RN, MSN, AOCN.

Email: khalid.alfaqih@iah.ps
 introduction
• Cancer: is a disorder or altered cell growth
(Proliferation) and cell function (differentiation).
• The resulting process is called Neoplasia.
• Neoplasia: New growth.
1. “A neoplasm characterized by the uncontrolled
growth of anaplastic cells that tend to invade
surrounding tissue and metastasize to distant body
sites.”
2. “Any of a larger group of malignant neoplastic
disease characterized by the presence of malignant
cells. Each cancer is distinguished by the nature, site,
or clinical course of the lesion.”
 Introduction
• Normal tissue renewal, repair, and death involves:
1) Proliferation: new or replacement cells
through mitotic cell division
2)Differentiation: specialization cells
3)Apoptosis: programmed cell death

Well-
Undifferentiated
Progenitor cells differentiated
stem cells
cells
s
 • Controlled • Uncontrolled

Cancer cells
Normal cells

growth growth
• Communicate • Lose to
by chemical communicate by
signals chemical signals
• Have adhesion • Metastasis
molecules • Unspecialized
• Specialized cells
cells • No apoptosis
• Apoptosis
Growth Properties of Normal and Cancerous Cells
 ETIOLOGY OF CANCER

(1) The genetic and molecular mechanisms that are

involved and that characterize the transformation
of normal cells to cancer cells
(2) The external and more contextual factors such as
age, heredity, and environmental agents
 genetic and molecular mechanisms
1. Cancer-Associated Genes:
▫ Gene overactivity :
 Proto-oncogenes: which are normal genes that
become cancer-causing oncogenes if mutated
(Decrease growth factor–dependent signaling).
▫ Gene underactivity:
 The tumor suppressor genes, which, by being less
active, create an environment in which cancer is
promoted.
▫ Apoptosis control disorder
 Defect of apoptosis
10
 Carcinogenesis
• The process by which carcinogenic (cancer-
causing) agents cause normal cells to become
cancer cells is hypothesized to be a multistep
mechanism that can be divided into three stages:
1. Initiation
▫ Cells exposed to doses of carcinogenic agents
making them susceptible to malignant
transformation
2. Promotion
▫ Unregulated accelerated growth in already initiated
cells caused by various chemicals and growth factors
Carcinogenesis (cont.)

3. Progression
▫ Tumor cells acquire malignant phenotypic
(morphology) changes that promote invasiveness,
metastatic competence, autonomous growth
tendencies, and increased karyotypic (appearance of
chromosomes) instability.
Host and Environmental Factors Leading

• Heredity
• Hormones
• Carcinogens
▫ Chemical
▫ Radiation
• Oncogenic viruses
• Immunologic mechanisms
CHEMICAL AND ENVIRONMENTALAGENTS KNOWN
TO BE CARCINOGENIC
• Polycyclic • Food and Drugs:
Hydrocarbons: • Smoked foods
▫ Tars, and oils • Nitrosamines
▫ Cigarette smoke • Anticancer drugs
• Industrial Agents: (e.g.,alkylating
▫ Asbestos agents, cyclophos-
▫ Benzene phamide,
▫ Nickel and chromium chlorambucil,
nitrosourea)
Inflammation and Cancer
• Chronic inflammation is an important factor in
the development of cancer
▫ Cytokine release from inflammatory cells
▫ Free radicals
▫ Decreased response to DNA damage

Obesity and cancer

Adipose tissue is active endocrine and metabolic tissue
In response to endocrine and metabolic signaling,
adipose tissue releases free fatty acids
 Correlates with colon, breast, pancreatic, and endometrial
cancers
Viruses/bacteria and Cancer
• Hepatitis B and C viruses HCC
• Kaposi sarcoma herpes virus (KSHV)
• Human papillomavirus (HPV) cervex cancer
• Human T cell leukemia–lymphoma virus (HTLV)
• Helicobacter pylori
▫ Chronic infections are associated with:
 Peptic ulcer disease
 Stomach carcinoma
 Mucosa-associated lymphoid tissue lymphomas
 Invasion & Metastasis
• Invasion
▫ Cellular multiplication
 Mitotic rate vs. cellular death rate
▫ Mechanical pressure
▫ Release of lytic enzymes
▫ Decreased cell-to-cell adhesion
▫ Increased motility
 Intravasation (in circulation)
 Extravasation (out of circulation)
 Metastasis
• Spread of cancer from a primary site of origin to
a distant site
▫ Steps
 Direct or continuous extension
 Penetration into lymphatics, blood vessels, or body
cavities (intravasation)
 Transport into lymph or blood
 Transport to secondary sites
 Entry and growth in secondary sites (angiogenesis)
 Metastasis Mechanisms:
• Lymphatic spread:
- most common
- tumor emboli inter the lymph channels through
the interstitial fluids or by penetrating the
lymphatic vessels through invasion
- tumors arising in areas of the body with rapid &
extensive lymphatic circulation are at high risk
for metastasis
• Hematogenous spread:
- malignant cells that survive the hostile
environment of blood (circulation, insufficient
oxygenation, immune system) attached to the
fibrin, platelets, clotting factors
 Staging and Grading of Tumors
• Grading of tumors: involves the microscopic
examination of cancer cells to determine their level
of differentiation and the number of mitoses. By
Pathologist
▫ Cancers are classified as grades I, II, III, and IV
with increasing anaplasia or lack of
differentiation.
• Staging of cancers: uses methods to determine the
extent and spread of the disease.
- depend on T.N.M system
- Surgery may be used to determine tumor size and lymph node
involvement.
 TNM CLASSIFICATION SYSTEMT
T (tumor)
Tx: Tumor cannot be adequately assessed
T0: No evidence of primary tumor
Tis: Carcinoma in situ
T1–4: Progressive increase in tumor size or
involvement
N (nodes)
Nx: Regional lymph nodes cannot be assessed
N0: No evidence of regional node metastasis
N:1–3 Increasing involvement of regional lymph nodes
M (metastasis)
Mx: Not assessed
M0: No distant metastasis
M1: Distant metastasis present, specify sites
Tumor Productive
 Products produced by tumor :

Tumor antigens
 They are either or
Tumor products

(enzymes and hormones)

Tumor products are released in the serum of patients

Tumor Productive

a) Hormones :
- Human chorionic gonadotrophins (HCG) are secreted
in cases of choriocarcinoma
- Thyroxin (T3 & T4) is secreted in cases of cancer
of thyroid gland

b) Enzymes :
- Acid phosphatase enzymes in cases of cancer prostate

- Alkaline phosphates, lipase and amylase enzymes in

cases of cancer pancreas
 Tumor Productive
• Tumor antigen is an antigenic substance
produced in tumor cells, it triggers an immune
response in the host.

• Classification of tumor antigens:

1- Tumor-Specific Antigens (TSA)
2-Tumor-Associated Antigens (TAA)
 !!? Tumor antigen are useful
• Tumor markers
▫ Certain tumors have certain tumor antigens in
abundance, Which may lead us to detect of tumor cell

• Cancer vaccines
▫ Used in cancer therapy as tumor antigen vaccines
 vaccines against some oncoviruses
Tumor Marker
1) Alpha fetoprotein antigen (AFP) in cases of hepatoma

2) Carcinoembryoinic antigen (CEA) in gastrointestinal

tumors, tumors of biliary system and cancer breast

3) Cancer antigen 125 (CA 125) in ovarian carcinoma

4) Cancer antigen 15-3 (CA15-3) in breast cancer

5) Cancer antigen 19-9 in colon and pancreatic tumor

6) Prostatic specific antigen (PSA) in prostatic tumors

 27

Clinical Manifestations of Cancer

1-Tissue Integrity
▫ Compressed blood vessels, ulceration and necrosis,
effusion frank bleeding, and hemorrhage
▫ development of effusions (i.e.,fluid) in the pleural,
pericardial, or peritoneal spaces m
2- Systemic symptoms (B symptoms)
fever, weight loss, fatigue, and night sweats;

2- Paraneoplastic Syndromes
▫ Manifestations in sites not directly affected by the disease
Paraneoplastic Syndromes
• Endocrinologics Syndrome:
▫ inappropriate ADH, Cushing syndrome (Small
cell lung cancer)
▫ Hypercalcemia (Squamous cell cancers of the
lung, head, bone, neck, ovary )
• Hematologic
▫ Venous thrombosis (Pancreatic, lung, other
cancers)
• Neurologic
▫ Myasthenia gravis (Small cell lung cancer)
Clinical Manifestations of Cancer
• Pain
 Pressure, obstruction, invasion of sensitive structures,
stretching of visceral surfaces, tissue destruction, and
inflammation
• Fatigue
 Sleep disturbance, biochemical changes from circulating
cytokines, secondary to disease and treatment,
psychosocial factors, level of activity, nutritional status,
and environmental factors
• Syndrome of cachexia
 Anorexia, early satiety, weight loss, anemia,
and altered protein, lipid,
and carbohydrate metabolism
Clinical Manifestations of Cancer
• Anemia
 Chronic bleeding resulting in iron deficiency, severe
malnutrition, medical therapies, or malignancy in
blood-forming organs
• Leukopenia and thrombocytopenia
▫ Direct tumor invasion to the bone marrow causes
both leukopenia and thrombocytopenia
▫ Chemotherapy drugs are toxic to the bone marrow
• Infection
▫ Risk increases when the absolute neutrophil and
lymphocyte counts fall