5.7 - 5.8 Neoplasia Flashcards
What are physiological and pathological causes of hypertrophy?
What is the difference between hormonal hyperplasia and compensatory hyperplasia?
- Hormonal hyperplasia - increases functional capacity of a tissue when needed
- Compensatory hyperplasia - increases tissue mass after damage or partial resection
What causes pathologic hyperplasia?
Caused by excesses of hormones or growth factors acting on target cells no mutations in genes that regulate cell division and hyperplasia regresses if stimulation is eliminated hyperplasia is distinct from cancer - but pathologic hyperplasia may be a precursor to cancerous proliferatio
What happens in metaplasia?
- reversible change in which one differentiated cell type is replaced by another cell type.
- adaptive substitution of cells that are sensitive to stress by cell types better able to withstand the adverse environment chronic irritation or inflammation
How is cigarettes an example of causing metaplasia?
Cigarettes normal ciliated columnar epithelial cells of trachea and bronchi replaced by stratified squamous epithelial cells
What happens in Barett’s esophagus?
Barrett esophagus - metaplasia from squamous to columnar type
the esophageal squamous epithelium is replaced by intestinal-like columnar cells under the influence of refluxed gastric acid.
Reversible but if persistent may induce dysplasia which may progress to cancer
What happens in dysplasia?
- pre-malignant condition of cell proliferation
- cells within epithelium typically exhibit:
- increased epithelial proliferation atypical mitoses nuclear hyperchromasia and stratification irregularly clumped chromatin increased nuclear-to-cytoplasmic ratio a failure of epithelial cells to mature as they migrate to the surface
- gland architecture is frequently abnormal characterised by budding, irregular shapes and cellular crowding
- assumed that once initiated will inevitably progress(to cancer)
What are the characteristics of benign neoplasms?
- Lack capacity to invade local tissues
- Localised to their site of origin
- Well differentiated
- similar to tissue of origin
- Discrete, palpable and mobile
What are the characteristics of malignant neoplasms?
- Ability to invade and replace local normal tissue
- Potential to spread to distant sites (metastasise)
- Typically less differentiated
- Often difficult to resect by surgery (depending on stage of detection)
What is the characteristcs of anaplastic (less differentiated) cells?
- Polymorphic
- variation in size and shape
- Abnormal nuclear morphology including darkly stained nuclei (hyperchromatic), large nucleus to cytoplasm ratio
- Frequent mitosis and may also include atypical mitotic figures
- Loss of polarity observed as disorganised growth
- Ischemic necrosis due to insufficient blood supply due to rapid growth.
What is the geographic influence of getting cancer?
- genetic and environmental factors both play a role in the pathogenesis of cancer
- environmental factors thought to be more significant contributors in most common sporadic cancers
- widely accepted that < 10% hereditary
- in one large study the proportion of risk from environmental causes was found to be 65%, whereas heritable factors contributed 26% to 42% of cancer risk
What are the environmental causes of cancer?
- Smoking
- Polycyclic aromatic hydrocarbons Benzopyrenes
- Dietary
- Polycyclic aromatic hydrocarbons (burnt animal fats)
- Nitrosamine (cured meats; dietary nitrates and amines; colonic carcinoma)
- Aflatoxin B1(nuts; hepatocellular carcinoma)
- Alcohol
- Hormones
- Industrial
- Asbestos (mesothelioma) Aromatic amines and azo dyes (bladder carcinoma)
What are the causes of cancer from radiation?
- Non-ionising
- Ultaviolet light - especially UVB (more penetrating)
- Skin cancer; melanoma
- Thymidine dimers (DNA damage)
- Ionising
- Electromagnetic (gamma and x-rays) and particulate (a, b, protons and neutrons)
- X-rays - leukemia
- 131I -thyroid cancer
- DNA damage - Single and Double-stranded DNA breaks
Which viruses may cause cancer?
How is immunodeficiency a cause of cancer?
What are the methods of using histology to examine cancer cells?
- Excision or biopsy the periphery may not be representative and the centre largely necrotic
- appropriate preservation of the specimen fixative (commonly formalin solution)
- Needle aspiration
- aspirating cells and fluid with a small-bore needle, followed by cytologic examination of the stained smear
- Cytologic smears (Papanicolau or Pap) widely used to screen for carcinoma of the cervix
How can biochemical assays be used as a tumour marker for caner diagnosis?
- tumor-associated enzymes, hormones, and other tumor markers in the blood
- cannot be used for definitive diagnosis of cancer contribute to the detection of cancer. maybe useful in determining the effectiveness of therapy
- could be used to detect appearance of a recurrence
- prostate-specific antigen and prostate-specific membrane antigen = prostate cancer
- carcinoembryonic antigen = carcinomas of the colon, pancreas, lung, stomach, and heart
How can imaging be used as a way of diagnosing cancer?
- e.g. Positron-emission tomography
- Increased metabolic rate (glucose utilisation) of cancer cells
- uses short-lived isotope coupled to glucose
- 2-[F-18]fluoro-2-deoxy-d-glucose
- Other radioactive isotopes targeted to cell surface markers currently investigated
How can molecular diagnosis be used to detect cancer?
- PCR most commonly used
- amplification of HER-2/NEU in breast cancer
- BCR-ABL transcripts by PCR to measure residual leukemia cells in treated patients with CML
- Genome-wide profiling
- Microarrays - large-scale analysis of gene expression using DNA microarray technology
- RNA-Seq massive parallel sequencing
What is meant by the grading of cancer?
- Grading of a cancer based on the degree of differentiation of the tumor cells, number of mitoses, architectural features
- well-differentiated, mucin-secreting adeno- carcinoma of the stomach
- poorly differentiated pancreatic adeno- carcinoma
- typically classified into low and high grade not as clinically useful as staging
What is meant by the staging of cancer?
- based on size of the primary lesion extent of spread to regional lymph nodes the presence or absence of metastases
- American Joint Committee on Cancer Staging TNM system
- T = size of primary tumour. primary lesion is characterized as T1 to T4 T0 = in situ
- N = regional lymph node involvement. N1 to N3 denotes involvement of an increasing number and range of nodes
- N0 = no nodal involvement
- M = metastases
- M1 or M2 indicates the presence of metastases
- M0 = no distant metastases
How is non lethal genetic DNA damage a characteristic of genomic instability?
- Non lethal genetic damage is the heart of carcinogenesis
- Genetic damage or mutation may be acquired by the action of environmental agents such as chemicals, radiation or viruses or endogenous products of cell metabolism
- may be inherited in the germ line
- term environmental in this context involves any acquired defect caused by exogenous agents
- some may be spontaneous and stochastic = bad luck
How do DNA double stranded breaks and error prone repair contribute to genomic instability?
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How is knudson’s two hit hypothesis seen in retinoblastoma?
What is the cancer stem cell hypothesis?
- stem cells undergo asymmetric division
- Different cell types with different mutations
- All these cells have different tolerance to treatments
- Stem cells form other cancers
What are the classic hallmarks of cancer?
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Which epimutations are can cause cancer?
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How is clonal expansion and evolution seen in cancer cells?
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How is invasion seen in cancer cells?
What are the steps of metastasis in cancer cells?
What is the linear progression model of cancer?
What is the parallel progression model of cancer stem cells?
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How does the parallel progression model vs linear progression have implications for therapy?
What is the difference between benign neoplasms, malignancy and anaplasia?
