Neoplasia "New Growth", Irreversible
Benign vs malignant
Nomenclature
Tumour Immunology
Genetics & Cancer
Cancer aetiology
Molecular determinants
Animal models in cancer & therapeutic options
Basic concepts & definitions
Three categories
Epithelial
Mesenchymal
Round cells
Endoderm or ectoderm
Mesoderm
Haematopoietic cells (lymphocytes, mast cells, macrophages)
Benign
Malignant
No invasion
Well demarcated
No metastasis
Low mitotic rate
Often smaller
Ulcers & bleeding rare
Resemble tissue of origin
Locally invasive
Poorly demarcated
Metastatic
Rapid growth
Often larger
Often ulcerate & bleed
Pleomorphic nuclei
Poorly differentiated
Some genetic mutations confer hallmarks of malignancy
Sustained proliferation
Evade growth suppression
Resist cell death
Angiogenesis
Metastasis
Direct Effects
Benign not always harmless
Local organ erosion/compression
Obstruction
Mass effect -hindrance of movement
Mass effect - organ torsion
Haemorrhage & anaemia
Indirect effects
Hormones from functional tumours - ACTH from pituitary tumours, insulin secreting tumours
Hormone-like peptides - PTH-rP (hypercalcaemia & metastatic mineralisation)
Systemic Effects
Well-defined cell borders
Round to ovoid in shape
Don't adhere to one another
Generally poorly defined cell borders
Spindle shaped
Mild to moderate adherence to one another
Forms streams & whorls in histology & loose, uneven clumps in cytology
Generally produce matrix (and the matrix helps us to decide what type of cell it is)
Strong adherence to one another
Form nests, islands, clusters
Mesenchymal Cells
Fibroblasts
Osteoblasts
Chondrocytes
Endothelial cells
Adipocytes
Skeletal muscle cells
Schwann cells
Round cells - WBCs
Mast cells
Macrophages
Plasma cells
Lymphocytes
Melanocytes
Epithelial cells
Epidermal keratinocytes
Gastric mucosal epithelial cells
Hepatocytes
Renal tubular epithelial cells
Mammary glandular epithelium
Epithelial
Benign -oma, papilloma (if papillary), adenoma (if glandular)
Malignant (carcinoma)
Mesenchymal
Benign -oma
Malignant (sarcoma)
Round
Benign (Histiocytoma)
Malignant - Lymphoma, Mast cell tumour, Melanoma
A tumour is formed by clonal expansion of a single precursor cell - incurred genetic damage (i.e. tumours are clonal)
4 classes of normal regulatory genes
Growth promoting proto-oncogenes
Growth inhibiting tumour suppressor genes (TSG)
Genes that regulate programmed cell death (apoptosis)
Genes involved in DNA repair - principal targets of cancer-causing mutations
Excessive increase in normal functions of encoded gene product
Gain of function
Loss of function
Both alleles damaged before transformation can occur
Abnormalities that result is less death
TP53
A tumour suppressor gene that regulates cell cycle progression, DNA repair, apoptosis
Loss of P53
DNA damage goes unrepaired
Driver mutations accumulate in oncogenes & other cancer genes
Active p53 upregulates expression of proteins e.g. cyclin dependent kinase inhibitor p21, causing cell-cycle arrest at G1-S checkpoint
Pause allows cells to repair DNA damage
Inactivated by viral oncoproteins, e.g. E6 protein of HPV
Steps involved in chemical carcinogenesis
Initiation then promotion (selection pressure)
Initiation results from exposure of cells to a sufficient dose of a carcinogenic agent; an initiated cell is altered
Permanent DNA damage (mutations); rapid & irreversible
Clinical aspects of Neoplasia
Local & Hormonal Effects
Cancer cachexia
Equal loss of both fat & lean muscle
Elevated basal metabolic rate
Systemic inflammation (e.g. an increase in acute phase reactants)