CELLULAR ABERRATION

TERMS
● Cancer – a disease process that begins when an abnormal cell is transformed by the genetic
mutation of the cellular DNA
● In cancer, the abnormal cell forms a clone and begins to proliferate abnormally, ignoring
growth-regulating signals in the environment surrounding the cell
● Hyperplasia
● Metaplasia
● Dysplasia
● Anaplasia
● Neoplasia – new growth; tumor; can be benign or malignant; uncontrolled cell growth that
follows no physiologic demand
● Benign – not malignant; an abnormal growth that is stable, treatable and generally not life-
threatening
● Malignant – cancerous; cells that are invasive and tend to metastasize, uncontrollable or
resistant to therapy; rapidly spreading Invasion – refers to the growth of the primary tumor into
the surrounding host tissues
● Metastasis – the dissemination or spread of malignant cells to distant sites by direct spread of
tumor cells to body cavities or through lymphatic and blood circulation

Characteristics of Benign and Malignant Neoplasms

Characteristics Benign Malignant

Cell characteristics Well-differentiated that resemble Cells are undifferentiated and

normal cells of the tissue from often bear little resemblance to
which the tumor originated the normal cells of the tissue
from which they arose

Mode of growth Tumor grows by expansion and Grows at the periphery and
does not infiltrate the sends out processes that
surrounding infiltrate and destroy the
tissues; usually encapsulated surrounding tissues

Rate of growth Usually slow Variable and depends on level

of differentiation; the more
anaplastic the tumor, the faster
its growth

Metastasis Negative Gains access to the blood and

lymphatic channels and
metastasizes to other areas of
the body

General effects Is usually a localized Often causes generalized

phenomenon that does not effects, such as anemia,
cause generalized effects weakness, and weight loss
unless its location interferes with
vital functions

Tumor destruction Does not usually cause tissue
damage unless its location
interferes with blood flow
Often causes tissue damage as
the tumor outgrows its blood
supply or encroaches on blood
flow to the area; may also
produce substances that cause
cell damage

Ability to cause death Does not usually cause death Usually causes death unless
unless its location interferes with growth can be controlled
vital functions
Fibroadenoma - are common, benign (non-cancerous) breast tumors made up of both glandular
tissue and stromal (connective) tissue.
- Sphere shaped with a smoother surface than most malignant breast cancers.

Invasion and Metastasis

1. Cancer cells invade surrounding tissues
and blood vessels.
2. Cancer cells are transported by the
circulatory system to distant sites.
3. Cancer cells reinvade and grow at new
location.
Terms
● Carcinoma – term used for malignant tumors of epithelial in origin (bronchogenic carcinoma,
invasive ductal carcinoma, endometrial carcinoma, adenocarcinoma, squamous cell
carcinoma, basal cell carcinoma)
● Sarcoma – term used for malignant tumors of mesenchymal/ connective tissue in origin
(rhabdomyosarcoma, liposarcoma, leiomyosarcoma, angiosarcoma)
● Note: benign tumors usually end with the suffix “oma”, except for lymphoma, hepatoblastoma,
neuroblastoma, myeloma, melanoma. These are already malignant
● Solid tumor – an abnormal mass that does not contain cyst or liquid.
Example of conditions : breast cancer, colorectal , neuroblastoma, Wilms tumor, uterine,
brain, lung cancer
● liquid – mass that contain liquid.
Example: Lymphomas ( Hodgkin and non- Hodgkin), leukemia

****Fibroadenoma – solid tumor

****Fribrocystic change, breast – cystic/liquid tumor

Terms
● Angiogenesis – the growth of new capillaries from the host tissue by the release of growth
factors and enzymes such as vascular endothelial growth factor (VEGF)
● Mutation – an alteration in a DNA nucleotide sequence – the order of the four bases adenine
(A), cytosine (C), thymine (T), and guanine (G)
● Mutations can alter both the sequence of a gene and its regulatory sites
● Tumor suppressor genes – normally suppress or negatively regulate cell proliferation by
encoding proteins that block the action of growth-promoting proteins
Quantitative Approaches to Cancer Research
● Vascular tumor growth
● Angiogenesis
● Cancer stem cells
● Intracellular signaling
Terms
● DNA-repair genes – the “caretaker genes” – genes involved in controlling or regulating
genetic instability to ensure integrity of genetic information
● Oncogenes – genes that encode proteins (oncoproteins) whose action promotes cell
proliferation

TUMOR SUPPRESSOR GENES

→ Hallmark characteristic of a mutated tumor suppressor gene is loss of function through:
1. Loss of genetic material
2. Loss of information
→ Examples:
a. APC, MEN1, p53, RB, and WT1 – affect DNA transcription
b. BRCA1 and BRCA2 – play roles in DNA repair
c. RB, p16 and TP53 – critical for the operation of the cell cycle, suggesting that many tumor
suppressor genes act as “gatekeeper” genes
SOME EXAMPLES OF GENES IN CANCER

SUSCEPTIBILITY
● ALDH2 – alcohol-related cancers
● APC – colorectal cancer
● CCND1 – head and neck cancer
● COMT – breast cancer
● CYP1A1 – lung, oral, and breast cancers, childhood leukemias
● GSTM1 - bladder and breast cancers; lung cancers
● HRAS – breast, ovarian, lung and colorectal cancer risk
● LTA – myeloma
● MCIR – melanoma

THEORIES AND RESEARCH MODELS

Key Points of Major of Tumorgenesis

Theory Key Points

Multistep Initiation:
● Stem cell becomes initiated by acquiring one or more
mutations, leading to partial escape from normal
homeostatic control
● Genetic mutations or epigenetic events responsible
● Irreversible
Promotion
● Initiated cell stimulated to proliferate but not terminally
differentiate
● Initiated cell acquires further genetic changes required for
neoplasms
● Interruptible and sometimes reversible

Mutagenic versus epigenetic
MODELS OF TUMOR
Nature versus nurture
Oncogene and Tumor
suppressor gene
Stem cell versus de-
differentiation
Properties of cancer
Property
Altered cell growth
Progression
● Malignant conversion of cell
● Confers autonomous growth of initiated cell
● Irreversible
Mutagenesis
● Results in qualitative or quantitative alteration information
● Chronic insults produce two to three mutations in individual
cells within particular tissues
● These mutations initiate tumors
Epigenetic process
● Chronic insults repeatedly injure and transiently excite many
cells in particular tissues
● These insults alter expression of genetic information at the
transcriptional, translational, or posttranslational levels
● Mutations are secondary events
Tumors suppressor genes: When mutated, do not stop unregulated
cell growth, induce differentiate, or undergo apoptosis
Stem cell
● Pluripotent stem cells restricted to allow a finite number of
cell to only specific lineage of cell types within the organs
that arise from the stem cells
● Daughter (progenitor) cells of these pluripotent stem cells
would give rise to terminally differentiated cells of that
lineage
Dedifferentiation: Some progenitor cells could revert back to a
pluripotent cell
Characteristics of Cancer Explanation
and Transformed Cells
Immortality Telomeres (DNA segments at
the ends of chromosomes) limit
the number of cell doublings.
Telomeres shorten with each
chromosomal replication until
reaching a threshold at which
cells senesce. Telomere stability
is critical for cancer progression.
Many cancer cells contain
telomerase, an enzyme that
prevents telomere shortening
and enables the cell to replicate
indefinitely
Altered cell growth Decreased density- dependent
growth inhibition (loss of contact
inhibition)
Altered cell growth Decreased requirement for
serum
Altered cell growth Loss of anchorage- dependent
growth
Loss of cell cycle control
Reduced apoptosis
Normal cells stop growing when
they contact other cells crowding
from contact compromises
access to nutrients
Transformed cells do not
respond to physical contact and
with chemical signals from
neighboring cells, thereby
continue to grow beyond normal
limits
Loss of contact inhibition
may result from a faulty
restriction point
Serum normally provides growth
factors necessary for cell
development and survival
Typically, the growth
factor binds to a receptor
on the cell surface, which in turn
activates the intracytoplasmic
portion of the receptor to send a
message to the nucleus (signal
transduction), where an effect on
gene function occurs.
Sometimes, an abnormal growth
factor receptor on the surface of
cancer or transformed cell can
activate the signal pathway
spontaneously without exposure
to growth factor
Cancer and transformed cell
lines may grow in media without
serum, suggesting that they can
synthesize and secrete their own
growth factors (autocrine
stimulation)
Cells require a substance to
grow. Transformed cells do not
require a solid substrate
Only tumor cells grow in soft
agar (no anchorage); cell growth
in soft agar is highly correlated
with
tumorigenicity
Cell does not progress normally
through cell-cycle pathways and
checkpoints
Cancer cells are less susceptible
to programmed cell death
Changes in cell membrane New surface antigens Cancer and transformed cells
exhibit new molecules on the
surface Viruses can transform
and alter multiple cell- surface
antigens

New or altered glycoproteins Transformed cells usually have

(proteins with polysaccharides)
profound changes in cell-surface
glycoproteins Some changes
may alter cell-cell and cell-matrix
adhesions
Mechanism by which
polysaccharides are made and
attached to proteins is deranged
in transformed cells

New or altered glycolipids Content and complexity of

glycolipids are reduced in
transformed cell membranes
Glycosphingolipid interacts with
receptor proteins on the surface
of normal cells to inhibit their
responsiveness to growth
factors
Transformed cells have less
and/or altered glycosphingolipids
on their cell surfaces, increasing
their responsiveness to growth
factors. Glycosphingolipids also
serve as components of surface
markers involved in normal cell
growth

THE CELL CYCLE

● A malfunction of any of these regulators
of cell growth and division can result in
the rapid proliferation of immature cells
● In some cases these proliferating
immature cells are considered
cancerous (malignant)
● Knowledge of the cell cycle events is
used in the development of
chemotherapeutic drugs, which are
designed to disrupt the cancer cells
during different stages of their cell cycle
CARCINOGENESIS

Three-step process
1. Initiation – initiators (carcinogens), such as chemicals, physical factors, and biologic agents
escape normal enzymatic mechanisms and alter the genetic structure of the cellular DNA
2. Promotion – repeated exposure to promoting agents causes the expression of abnormal or mutant
genetics information
3. Progression – the altered cells exhibit increased malignant behavior; they now have the
propensity for invasion and metastasis

Etiology
a. Viruses and bacteria
b. Physical agents
c. Chemical agents
d. Genetics and familial factors
e. Dietary factors – fats, alcohol, salt-cured or smoked meats, nitrate-containing and nitrite containing
foods, red and processed meat
f. Hormonal agents – DES, OCP and prolonged progesterone therapy
DIETARY FACTORS
● Alcohol increases the risk of cancers of the mouth, pharynx, larynx, esophagus, liver,
colorectum, and breast
● Greater consumption of vegetables and fruits is associated with decreased risk of lung,
esophageal, stomach, and colorectal cancers
● High caloric dietary intake is also associated with an increased cancer risk
● Obesity is clearly associated with endometrial cancer, postmenopausal breast cancers, and
colon, esophagus, and kidney cancers, as wells as pancreatic cancer, gallbladder, thyroid,
ovary, cervix, prostate cancer, and multiple myeloma
GRADING VERSUS STAGING
● Grading – identification of the type of tissue from which the tumor originated and the degree to
which the tumor cells retain the functional and structural characteristics of the tissue of origin
● Staging – process of determining the extent of disease, including tumor size and spread or
metastasis to distant sites
● TNM Staging
T – primary tumor
N – regional nodal metastasis
M – distant metastasis

TNM CLASSIFICATION SYSTEM

● Primary tumor
Tx – Primary tumor cannot be assessed
T0 – No evidence of primary tumor
Tis – carcinoma in-situ
T1, T2, T3, T4 – increasing size and/or local extent of the primary tumor
● Regional lymph node metastasis
Nx – Regional LN cannot be assessed
N0 – No regional LN metastasis
N1, N2, N3 – Increasing involvement of regional LN
● Distant metastasis
Mx – Distant metastases cannot be assessed
Mo – No distant metastases
M1 – Distant metastases

4.61 cm
CANCER WARNING SIGNS AND SYMPTOMS
● C change in bowel habits sign of colorectal cancer
● A sore that does not heal on the skin or in the mouth could be malignant
● Unusual bleeding or discharge from rectum, bladder or vagina could be colorectal, prostate,
bladder or cervical cancer
● Thickening of breast tissue or a new lump in breast
● Indigestion or trouble swallowing cancer of the mouth throat esophagus or stomach.
● Obvious changes to moles or warts could be skin cancer
● Nagging cough or hoarseness that persists for four to six weeks could be cancer of lung or
throat cancer.

OTHER MANIFESTATIONS OF CANCER

● Impaired immunity
● Hemorrhage
● Anemia
● Anorexia-cachexia syndrome
● Paraneoplastic syndromes – indirect effects of cancer
○ a. Breast, ovarian, and renal cancers may set up ectopic parathyroid hormone sites,
causing severe hypercalcemia
○ b. Oat cell and lung cancers may produce ectopic secretions of insulin, PTH, ADH, and
ACTH
● Pain
● Physical stress – when the immune system discovers a neoplasm, it tries to destroy it using
the resources of the body
● Psychologic stress

ROLE OF THE NURSE

● caregiver
● advocate
● case manager
● educator
● change agent
● counselor
● educator
● epidemiologist