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)