Neoplasia Flashcards
What is neoplasia
Uncontrolled cell growth that persists in absence of stimuli
What do cdks do?
activate downstream proteins by phosporylation
What happens to cells at G0 phase?
Are dormant and will only move onto differentiation, proliferation or cell death if they detect signals (eg ligands such as growth factors) from other cells
Permanent cells
Cannot duplicate (eg neurones, cardiac myocytes)
Conditionally-renewing cells
Will proliferate and differentiate to repair injury (eg hepatocytes)
Labile tissue
Constantly dividing in health (eg epithelia and bone marrow)
Hypertrophy
Increase in cell size and hence organ size
Hyperplasia
Increase in cell number and hence organ size (eg lactating breasts, prostate enlargement with age)
Organ architecture maintained and proliferation stops when stimulus removed
Metaplasia
One differentiated cell becomes another due to persistent injury, but reverses once injury removed (eg bronchus due to tar)
Dysplasia
descriptive appearance, not stage
Irreversible cytological changes in neoplasia
Invasion
Neoplasm infiltrates surrounding tissue and/or organs
Metastasis
Neoplasm spreads to other parts of the body via the blood, lymph or body spaces and proliferates
Benign
Neoplasm proliferates but does not invade or metastasise
Benign tumour classifications
Surface epithelia=papilloma Glandular epithelia= adenoma Fat= lipoma Fibrocytes=fibroma Cartilage=chondroma Smooth muscle= leiomyoma Skeletal muscle= rhabdomyoma Bone=osteoma Germ cells/gonads= teratoma
Malignant tumour classifications
Surface epithelia= squamous cell carcinoma Glandular= adenocarcinoma Germ cells/gonads= teratocarcinoma Skin= melanoma Lymph nodes= lymphoma Astrocytes= glioma WBC= leukaemia Connective tissue= sarcoma
How can tumours cause death
Destruction of vital tissue, haemorrhage, opportunistic infection
Carcinoma in situ
Neoplasm just before stage of invasion
Carcinoma vs sarcoma
Carcinoma= forms in skin or tissue cells that line body’s internal organs (most common)6
Sarcoma= grows in body’s connective tissue cells
What is TNM?
Cancer staging system (stands for tumour, node, metastasis)
Scores tumour size, lymph node involvement and extent of distant metastases
Cancer grading
1-3, graded by degree of tissue differentiation (3=worst)
Oncogenesis
Development of a tumour
Also carcinogenesis
Oncogenes
Normal genes which, if mutated, cause cancer (often regulatory genes)
Mechanisms of oncogene activation
- retrovirus inserts oncogenes into host cell genome or introduce viral promoters (so transcription factors express host genes inappropriately)
- Ras genes can become oncogene through point mutation (causing Ras molecular switch to be permanently active)
- epidermal growth factor receptor (EGFR) can become overly active by amplification or truncation
- growth factors (eg sis) can be altered
Tumour suppressor genes (TSGs)
- Retinoblastoma (Rb) codes for pRb protein which must be phosphorylated in cell cycle by CDK for cell to pass from G1 to S phase, Rb blocks progression through cell cycle by binding to transcription factor E2F
- p53 protects genome, conc. of p53 increases when DNA is damaged, acts as transcription factor for CDK inhibitor (p21), meaning p21 can’t phosphorylate Rb (resulting in cell cycle arrest), if damage irreparable then apoptosis occurs
- APC is regulatory protein in Wnt ligand pathway, regulates B-catenin which acts as transcription factor for growth promoting genes
Stroma
Supporting vascular connective tissue surrounds organs and sarcinomas
Angiogenesis
Blood vessel growth (essential for tumour growth)
In which condition are nucleotide excision proteins mutated?
Xeroderma pigmentosum (damaged DNA results in skin cancer)
What happens when viral oncogenes activate telomerase?
Cells become immortal as telomerase enzymes make new repeat sequences on telomere
Hallmarks of cancer
- self sufficiency in growth signals
- insensitivity to growth inhibition signals
- evasion of apoptosis
- immortality
- angiogenesis
- invasion and metastasis
Pleomorphism
Larger cell nuclei
How to identify cancerous cells on pathology slides
Lesions, cells crowded (sometimes with mucus), hyperchromasia (darker staining nuclei), variation in cell size/shape, reduced differentiation, loss of cell polarity, abnormal and increased mitosis
Causes of cancer
- viral transduction transforming DNA using oncogene (RAS switch)
- deletion of TSG (proliferation no longer inhibited/ apoptosis no longer promoted, oncogene activated)
- defects in DNA repair gene (eg. those coding for mismatch repair proteins)
- electrophiles activated from chemical carcinogens
- tar metaplasia from smoking
- radiation: eg. UV rays may cause DNA strand breaks or thymine dimers (disrupting base pairing)
Cancer Risk factors
Increased age, smoking, genetic predisposition, environment (incl. carcinogen exposure) radiation exposure, infectious agents (viruses), parasites
Cancer treatment
- Surgery
- chemotherapy (metastasised)
- radiotherapy
- bone marrow transplants
- angiostatic agents
- pain relief
- palliative care
- immunotherapy
What is immunotherapy?
Treatment used to stimulate immune system to recognise cancer cells as foreign and attack them
How to tell difference between benign and malignant tumour
Benign: clearly circumscribed, not extended into tissue but into lumen (exophytic growth)
Malignant: messy, crab-like spread into affected tissue (endophytic growth)
Polyps
Abnormal outgrowths connected to affected tissue by a stalk
