Cancer Flashcards
Cancer
uncontrolled cells that can grow and spread to different parts of the body
Tumour
Abnormal swells (not necessarily cancer) same as neoplasm
Neoplasm
Lesion = autonomous growth or relative abnormal growth of cells that then persists in absence of stimulus
Histogenesis
The differentiation of cells into specialist tissues and organs
Histogenic Classification of Tumours (definition)
The cell, tissue or organ of origin - NOT the organ/ tissue it is now in (mets)
Most common cancers (4) in order
Breast/Prostate
Lung
colorectal
Most fatal (4) in order
Lung
Prostate/ breast
Colorectal
Classification of tumours - rate of growth (3 ways)
Doubling time (number of cells double)
% cells in replicating pool
Rate at which cells die/ shed
Differentiation
the extent that neoplasmic cells represent normal parenchymal cells
BOTH morphologically and functionally
Grade? = how differentiated?
Grade 1 = well differentiated
Grade 2 = moderate differentiated
Grade 3 = poorly differentiated
Grade 4 = anaplastic (not differentiated)
Pleomorphic
cells the vary in shape and size (from normal cells)
Abnormal nuclei
Can be too large
Vary in shape
Chromatin distribution variation (3)
Coarsely clumped
Along cell membranes
Hyperchromatism = stain darkly
Abnormal Mitosis? Mitosis = indicator of proliferation and turn over rate
1) asymmetrical bikaryokineses
2) Trikaryokineses
3) tetrapolar division
4) Multipolar
1) asymmetrical separation of condensed chromosomes
2) organisation of chromosomes into 3 groups
3) organisation of chromosomes into 4 groups
4) Multiply spindle fibres
Loss of polarization?
orientation of cells disturbed
disorganized growth
Classification of tumours by invasion? (stage)
Benign
Malignant
Benign = encapsulated expansible mass, no infiltration or mets
Malignant = local invasion into adjacent structures, no boundaries, mets
Metastasis? (staging)
Spread of tumour to site NOT physically attached to site of origin
Mets are associated with? (5)
Poorer prognosis Less differentiation increased size local invasion rapid growth
Met pathways (3)
Direct seeding
Lymphatic drainage
Venous pathway
Direct seeding met process?
Transcoelomic
eg. Colonic cancers
Penetration natural open field (eg. Open cavity) and remain adhere to surface with in it - eg. peritoneal mets
Lymphatic spread mets process?
Follow lymph node drainage
Senital nodes –> distant nodes
Stroma ?
connective tissue framework the solid tumours are embedded in
Contains blood vessel, lymphatics, fibro and myofibroblasts
Desmoplasmic reaction?
stroma formation due to fibroblast proliferation by growth factors from tumours
Complications - local?
Compression eg. pituitary on CN2 = visual defects
Destruction eg. ulceration on mucosal surfaces
Complications - metabolic?
General (4)
Specific
General = cachexia (weaknes), Neuropathies and loss of endocrine function, myopathies (muscle fibers)
Specific examples for neurological and endocrine
Histological classification of tumours
Make up the names include reference to:
Cell type - tissue type - benign or malignant
Pampilloma
Bengin non glandular surface epithelial tumour (cell type before)
Adenoma
Benign tumour of the Glandular endothelial (Tissue type before)
Carcinomas
Malignant non glandular surface epithelial tumour (add cell type before)
Adenocarcinomas
Malignant glandular epithelial tumour
Urothelial carcinoma
Malignant epithelial bladder cancer
Benign mesenchymal (connective tissue) tumour
__ oma (proceeded by tissue of origin)
Sarcomas
Malignant mesenchymal (connective tissue) tumour - proceeded by tissue of origin
Liposarcoma
Malignant tumour of adipose
osteoma
benign tumour of bone
Melanocytic lesions
pigment tumour of the epidermis
Benign Melanocytic lesion
Melanocytic naevi - freckles or patchy pigments of skin
Melanoma - Malignancy measured by ABC?
asymmetrical shape, irregular Boarders and inconstant Colour
Leukaemias
cancers of blood cells or in the bone marrow
Lymphomas
lymph nodes and solid organs BUT also lymphocytes in blood (cross over with leukaemias)
Myeloma
plasma cells tumour
Special features of brain tumours (3)
Can not break through basement membrane
Can’t metastasise BUT can have mets in it (from elsewhere)
Benign tumours are very harmful due to increase ICP
Examples of Brain and CNS tumours (4)
Meningiomas
astrocytomas
oligodrendroglioma
Pituitary tumours
Where do germ cell tumours normally arise
Gonades
Midline - due to germ cell migration
Ovarian Germ cell tumours
dysgerminoma
Sperm germ cell tumours
seminoma
Embryonal tumours - resembled? named after?
pediatric tumors of not fully differentiated cells
Resemble to embryonic cells of the organ it is destined to be BUT named after organ of origin
_blastomas
Emryonal tumours (due to not being fully differentiated) Preceeded with tissue of origin
Harmatomas
non neoplastic tissue overgrowth = benign
Confused with tumours
Insidious and idiopathic
Choristoma
heterotopic - tissue types in the wrong site.
Non neoplastic and benign
Primary
tumour is at site of origin
Secondary (met)
not at site of origin BUT still named after primary tissue type/ organ
Cancers of unknown primary source (3 reasons)
Occult primary - unknown or too small to see
Migrating pre malignant stem cells
Regressed primary tumour
Malignant tumours with benign names (4)
Melanoma (skin cancer)
Mesothelioma (mesothelium)
Myeloma (plasma)
lymphoma (lymphocytes)
Exposure to carcinogens (3)
Geographic - environmental (UV light)
Occupational - eg. silica dusts
Accidental - lab tests or radiations
Types of carcinogens (6)
Chemicals infectious agents Radiation Minerals Physiological - hormones Chronic inflammation
Carcinogens
any agents the significantly increase the risk of developing cancer
Initiator carcinogens
Genotoxic
Damage/ modify the DNA = exasperating tendency for polymerases to make mistakes
Promotors carcinogens
non-genotoxic
Induce proliferating and DNA replication = clonal expansion of mutated cells
(after 2 rounds of replication = mutation is fixed)
Complete carcinogens
both promote and initiated
Result of mutations (2) - which genes altered
Gain of function - activation of proto-oncogenes
Loss of function - inactivation of tumor suppressor gene
CpG islands are associated with?
promotor regions that are methylation –> turns off the gene
Tumor suppress genes are associated with?
Famillia cancers
Procarginogens - how taken in?
example
carcinogens (usually ingested) that require enzymatic activation
Benzopryene - found in meat, tobacco and fuel
3 examples of DNA repair - which carcinogen they repair
Nucleotide-excision repair (NER) = UV light, hydrocarbons
Recombinantional repair = X-rays
Mismatch repair = replication agent
Proto-oncogene - what do they do
promote cell cycle Proliferation, growth, survival and angiogenesis
How does mutation affect Proto-oncogenes?
activates them to oncogenes
Oncogenes - what do they do? (2)
Dominant - one mutated allele and one mutational ‘hit’ to be expressed
Increase expression of oncogenes = controlled growth and protein development
Aberrent (diversion for normal cell type) proliferation
Mechanism of proto-oncogene activation (4)
Translocation = low to high transcriptional state
Point mutation = hyperactive
Amplification = more oncogenes –> increased expression
Insertion - of a promoter sequence
Oncoproteins - coded for by oncogenes = functions (3)
Growth factor receptors
Bind to DNA to stimulate transcription
Secondary messenger that activates the cells cycle
Tumor suppressor genes (2 types + what they do)
‘gatekeepers’ - negative regulator of cell proliferation
OR
‘caretakers’ - repair DNA so defect DNA doesn’t replicate
Mechanism of Tumor suppressor deactivation? (3)
Recessive - two mutation ‘hits’ for mutated tumor supressor to be expressed
point mutations
deletions
epigenetic silencing - by methylation on CpG promoter regions
Example of TSG (3)
RB1 - retinoblastoma
p53 - Li- Fraumai (Breast sarcomas)
APC - Famillial adenomatous polyposis (colorectal)
Examples of Caretaker genes (2)
BRACA1 and BRACA2 = familliar breast caner
hMLH1 and hMLH2 = familliar non-polyposis colorectal cancer
Minimum number of mutations (germline or somatic) for carcinogenesis
3
Hallmarks of cancer - acquired functional capabilities (6)
Self sufficent growthpathways
Insensitivity to antigrowth factors
Immortality - talomeres on the end of chromosome never diminish in length = can replicate multiple times
Resistant to apoptosis
Sustained angiogenesis
Local invasion (basement membranes) and mets
How do tumor cells self stimulate growth? (names of genes that mutate)
Over expression of EGFR (growth factor receptor)
RAS and RAF mutations = produces proliferating proteins
Mutation that causes resistance to anti-growth factors?
Rb (gatekeeper) = inactivated
Telomerase ?
Is over expressed in tumor cells so chromosomes always have telomere = replicate infinite number of times
Mutation that makes tumour cells resistant to apoptosis
T53 = normally cause cell cycle arrest followed by DNA repair OR apoptosis of faulty cells
Size of tumors that can sustain angiogenesis
2 mm
How do tumour cells invade and metastasis
Mutation in gene = loss of E-cadherin –> motile
Secrete proteases = pass through basement membranes
Genetic screening
Cancer predisposition
Tumor markers for diagnosis? - type of cancer
Raised PSA in the blood (prostate specific antigen)
Predictive markers for therapeutic response/ targeting drugs?
HER2 growth factor receptor over expressed in breast caner and responsive to Herceptin
Tumor markers for monitoring response to treatment?
CA-125 in ovarian cancer
5 clinical applications of tumor markers
screening diagnosis prognosis therapy monitoring
Dysplasia
abnormal differentiation
Anaplasia
no differentiation
Epithelial become _____ cells in tumors
Mesenchymal cells (as these are not adhered and able to move even in health)
Mutation in
Ecaderhins
Intergrin expression
in epithelial cells Cause?
E-caderhins = loss of cell to cell adhesion Intergrin = loss of cell to matrix adhesion
Matrix Metalloproteinases
eg. gelatinases, stomolysins
degrade the basement membrane and collagen in the extra cellular matrix
Mechanical pressure and the effect on the behavior of the tumor (6 step process)
No contact inhibition
Mass = pressure = occlude vessel = ischemia and death –> tumor then moves along line of weakness
Cancer that metastasis via lymphatics firstly
carcinomas
Cancers that met via blood (firstly) + from where?
Sarcomas from liver, lungs, bone and brain
Process of Blood spread of Mets? (4 stages)
Tumor locally invades a blood vessel –> cells break off –> carried to narrower vessel –> embed and cause secondary tumor
Implantation spread of mets?
Accidental deposit of cells during resection/ other surgery
‘seed and soil’ theory
The idea that cancer cells have to find an ideal tissue environment to met is = organ selectivity for mets
Angiogenesis
- part of healing process (physiological)
New vessel formation (derived from existing vessels)
Growth factors released by tumor cells that control angiogenesis
VEGF
PDGF
TGFBeta
Vascular endothelial growth factor
platelet derived growth factor
Transforming growth factor beta
Staging (3 components)
How big the primary tumor is
How far its spread
Any mets?
TMN staging? (all 1 - 4)
T = tumor - size of primary and how far spread M = mets - how many and how far N = nodes - how many and how far
Dukes staging? - what cancer?
Colon cancer
Ann arbor stages for Lymphoma
LN = lymph nodes
1 = one lymph in isolation 2 = 2 physically unasocciated LN 3 = Multiple unassociated LN - at least one on the oposite side of the diaphragm 4 = multiple unassociated LN
Grade
How differentiated the cells are = how aggressive
Less differentiated = more aggressive
Stage and Grade do what?
Diagnose and guide prognosis - surgery? chemo? years left?
