Cancer Flashcards
What is a tumor?
- An abnormal mass of tissue
~ Either benign or malignant - Uncontrollable/autonomous growth
~ Persists even after cessation of the stimuli that initiated it
What are the general characteristics of benign tumors?
- Typical of tissue of origin
- Well-differentiated
- Few mitosis and normal
- Strictly local, often encapsulated with no metastasis
~ Capsule and basement membrane not breached - Slow growth rate
- Rare tumor necrosis
- Rare recurrence after treatment
- Good prognosis
What are the general characteristics of malignant tumors?
- Anaplastic
~ With abnormal cell size and shape
~ Not well-differentiated - Many mitoses
- Rapid growth rate and may be abnormal
- Infiltrative/frequent metastases
~ Capsule and basement membrane breached - Tumor necrosis common
- Recurrence common after treatment
- Poor prognosis
What are the main phases of tumor development and growth?
1) Transformation
- Benign cells
~ Mostly well-differentiated
~ Resemble the cell from which they originated
- Malignant
~ Transforms into anaplasia (final stage)
~ Nuclear and cellular pleomorphism (size and shape)
~ Abnormal nuclear morphology
~ Loss of polarity
~ Abundant mitoses
2) Rate of growth of transformed cells
- How differentiated the cells are
~ Well-differentiated: Resembles mature cells of tissue of origin
~ Poorly-differentiated: Primitive cells
~ Undifferentiated: Anaplastic
- Less differentiated = faster growth
3) Invasion of tumor cells to surrounding tissues
- Benign cells
~ Cohesive with a rim of condensed connective tissue/capsule
- Malignant
~ Local invasion (Detachment, attachment, degradation & migration)
4) Metastasis of tumor cells to distant sites
- Lymphatic, hematogenous and seeds into body cavities
- Intravasation, embolisation, adhesion, extravasation, metastatic growth
What are the different ways that cells can transform in cancer?
HHN DMA (HHN Done More Amazing)
1) Hypoplasia
- Fewer cells than normal
~ Usually benign
- eg postpubertal female breast underdevelopment /micromastia
2) Hyperplasia
- More cells than normal
- Controlled by normal proliferation mechanisms
- Due to external stimuli
~ eg callus exposed to pressure
3) Neoplasia
- ^ cell number
- Abnormal multiplication
~ Loss of normal proliferation regulation
~ Absence of stimuli
4) Dysplasia
- Change in normal shape, size and organisation
- Usually in response to chronic irritation
- Reversible changes if stimulus is removed
~ If not, cells become metaplastic
5) Metaplasia
- Change in cell type
- After prolonged irritation
- Reversible changes if stimulus is removed
~ If not, cells become anaplastic
6) Anaplasia
- Reversal in differentiation OR
- Loss of structural and functional differentiation of normal cells
- Not reversible in nature
- Characteristic of cancerous tumors
What are some abnormal nuclear morphology?
- Hyperchromasia
- High nuclear cytoplasmic ratio
- Chromatin clumping
- Prominent nucleoli
What are the steps in local invasion of cancer cells?
1) Detachment of tumor cells from each other
2) Attachment of tumor cell to matrix components
3) Degradation of matrix components
- To allow slow invasion through
- eg using collagenase
4) Migration of tumor cells
What are the steps in metastasis?
Clonal expansion, growth, diversification, angiogenesis into metastatic subclone -> Adhesion to and invasion of basement membrane -> Passage through extracellular matrix -> (1)
1) Intravasation
- Passage of cancer cells into blood vessels
2) Embolization
- Interaction with host lymphoid cells forms a tumor cell embolus/clump which travels along the BV
3) Adhesion
- Embolus adhesion to the basement membrane
4) Extravasation
- Passage of cancer cells out of blood vessels into distant tissues
- Metastatic deposit
- Angiogenesis and growth
5) Metastatic growth
What is the significance of nodal metastasis?
T1N0M0:
- Small
- No spread to regional lymph nodes
- No metastasis
- Considered stage 1
T4N1M1:
- Large
- Spread to regional lymph nodes and other organs
- Considered stage 4
What is the nomenclature for cancers?
Benign:
- Suffix of -oma
- eg osteoma, lipoma, papilloma
Malignant:
- -carcinoma
~ If originated from epithelial cells
~ eg squamous cell carcinoma, adenocarcinoma
- -sarcoma
~ If originated from mesenchymal cells
~ eg fibrosarcoma, osteosarcoma, angiosarcoma
What are the predisposing factors for cancer?
- Age
- Childhood cancers
- Obesity
- Chronic inflammation
- Precancerous conditions
~ Chronic ulcerative colitis
~ Atrophic gastritis of pernicious anemia
~ Leukoplakia of mucous membranes - Genetic factors
~ Point mutation
~ Translocation
~ Amplification
~ Familial cancer symptoms - Environmental factors
What are the environmental factors that increases the risk of cancer?
- Chemicals
~ Hormones, grilled meats, asbestos - UV light/ionizing radiation
~ Usually causes basal cell carcinoma, squamous cell carcinoma, melanoma - Viral infx
~ HPV (squamous cell carc)
~ EBV (Burkitt lymphoma, NPGL carc)
~ HBV (hepatocellular carc) - Vices
What are the regulatory genes targeted in carcinogenesis?
- Proto-oncogenes
~ Normal genes that promote cell proliferation
~ Only switched “on” for short periods by growth-promotion factors
~ Mutates into oncogenes when damaged by carcinogens
~ Oncogenes are dominant and function autonomously
~ RAS genes, MYC genes, ABL genes - Tumor suppressor genes
~ Inhibits cellular proliferation
~ Stimulates apoptosis
~ BRCA1/2 genes, p53 genes, RB genes - Genes regulating apoptosis
- Genes revolved in DNA repair
What is the molecular basis of malignancy?
Failure of DNA repair or cell mutations ->
- Activation of growth-promoting hormones + Inactivation of tumor suppressor genes
~ Unregulated cell proliferation
- Alterations in genes that regulate apoptosis
~ Decreases apoptosis - Clone expansion + Angiogenesis + Additional mutations + immunity escape
~ Tumor progression and malignant neoplasm
