tumour pathology Flashcards
Describe the classification and nomenclature of tumours.
Tumours are irreversible, do not stop growing even when stimulus is removed.
Tumours are defined by the tissue they originate (usually epithelium) in and the whether they are benign or malignant.
Prefix- defines the tissue they originate from
Suffix- defines the type of cancer they are.
e.g. adenoma and adeno-carcinoma
Exceptions:
-WBC - leukemia
-Lymphatic system-lymphoma
-CNS- astrocytes
-PNS- schwannoma
-Germ cells- Teratomas. ( In ovaries usually benign, in testis-malignant)
-melanocyte- melanoma and naves(benign)
List the differences between benign and malignant tumours.
Benign:
- Non-invasive growth
- Encapsulated
- Do not metastasise
- Cells similar to normal
- Cell function similar to normal
- Do not cause cell death
- Well differentiated
Malignant:
- No capsule
- Invasive growth
- poorly differentiated
- Usually cause cell death
- Cell have abnormal function
- Metastasise
Define the properties of cancer cells.
-They inhibit tumour suppressor genes
-They stimulate proto-oncogenes
-They alter cell morphology: lots of pleomorphism (alter size) and abnormal mitosis
-They alter cell function: They prevent cell-cell adhesion, they alter cell-matrix adhesion, they produce tumour proteins.
-The tumour proteins are known as biomarkers and can be used in screening, diagnosis, prognosis and predictio.
different types of biomarkers: oncogenes, Onco-fetal proteins, growth factors and immune checkpoint inhibitors.
Specific biomarkers for different tumours
e.g. oestrogen receptors- breast
prostate antigens-prostate
alpha-fetoprotein- teratoma of the testis and hepatocellular carcinoma
carcino-embryonic antigen- colorectal
Define the spread of cancer and its mechanisms.
Balance of tumour growth depends of apoptosis and apogenesis ( formation of new blood vessels) Metastisis can occur by 4 methods: - local spread -lymphatic spread -Blood spread -trans-coelomic spread: across cavities
Does not depend on blood flow.
Depends on tumour type and tissue.
Common sites of metastasis are : the bone, the brain, the lungs , the adrenal gland
Uncommon sites: spleen, kidney, heart, skeletal muscle
List the local effects of cancer.
Benign: -Obstruction which can lead to pressure Malignant: -Obstruction -Pressure -Bleeding: in small vessels-anemia in large vessels- haemmorage -Tissue destruction- Ulceration or infection -Effects of treatment -Pain: tumour can apply pressure on nerves tumour can infiltrate perineurial system bone pain due to fractures
List the systemic effects of cancer.
Malignant:
- effects of treatment
- weight loss cachexia
- altered hormone production:
normal: produced by organs of the endocrine system but rate of production/secretion is altered
abnormal: produced by organs which do not usually produce organs e.g. ADH/ACHT in the lungs - paraneoplastic syndromes: not related to local or metastatic effects of cancer.,
Identify the concepts of dysplasia and intra-epithelial neoplasia.
Dysplasia: Earliest change in the malignancy which can be detected. -non-invasive -effects the epithelium: alters nuclear/cell size increased mitoses abnormal mitoses activity
Intraepithelial neoplasia: identification of a benign neoplasia or a high grade dysplasia
Outline early detection of cancer
Importance of screening. Obligatory testing carried out by the NHS: -cervical -breast -colon
Describe the cell cycle of normal cells.
G0- no growth stage
G1- DNA prepares to replicate
S- DNA is replicated
G2- organelles prepare for growth
Mitosis:
Interphase- DNA is replicated
P- chromosome condenses, nuclear envelope dissolves
M- chromosome condense further, align along equator and spindle form
A-spindle fibres attach to chromosomes at centromere and contract
T- chromatids reach opposite ends of the cell and two new daughter cells form
Outline the process of carcinogenesis and describe its effects on the cell cycle.
-Proto-oncogenes mutated to become oncogenes.
Oncogenes drive uncontrolled cell division.
-Tumour suppression genes are switched off which would otherwise control apoptosis.
-DNA repair genes are switched off.
-cell cycle regulatory systems are interrupted:
p53-
pRb
CELL CYCLE Regulators:
- A series of active and inactive enzymes.
- have a catalytic sub-unit (CDK) and a regulatory sub-unit (cyclin )
- they activate the target protein by phosphorylating them- which in turn activates their substrate which will alter the next stage of the cell cycle.
- CDK inhibitors also regulate the cell cycle. They bind to CDK sub-units and prevent them from binding to cyclin.in
-they stop the cell cycle when: nutrient supply, DNA replication, DNA mutation, cell size, chromosome misalignment.
List the major aetiological agents of cancer.
Environmental:
-radioactivity: UV/gamma/X-ray can affect purines and pyrimidines
-virus: virus can inject an oncogene into human DNA OR
virus can insert its genome into host proto-oncogene
e.g. HPV, Hep B-LIVER CANCER
-chemical: oxidising/alkylating agents can alter purines and pyrimidines. Adducts form when chemicals covalently bond to DNA. when they form at certain chromosome sites they can lead to cancer
e.g. Benzopyrene
- age
- hereditary e.g. tumour suppressor genes and two hit hypothesi– one gene inherited, one gene developed- leads to bilateral retinoblastoma. If both mutations occur within the same cell then it leads to unilateral retinoblastoma.
describe how the etiological agents cause abnormalities in the regulation of the cell cycle
Hereditary side: accounts for 5-10% of all familial cancers.
-inherited cancer syndromes e.g. strong family history of cancer at specific uncommon site or inheritance of single mutant autosomal dominant gene
-Familial cancer: strong family history of clusters of tumours at specific site but predisposition unclear. early onset. cancers may be unilateral or bilateral.
-autosomal recessive inherited mutant DNA repair gene
Proto-oncogene mutations:
-Alterations
point mutations (single nucleotide base is replace, inserted or deleted)
Chromosome rearrangements and translocations- over expression or formation of chimeric proteins (fusion of 2 genes which originally coded for 1 protein)
-Dysregulation
Gene amplification
Overexpression
Identify that tumour formation is a multi-step process.
Abnormalities accumulate with time.
In most cancers- two anti-oncogenes and several oncogenes develop
pRB
pRB is used as a break in the cell cycle.
When pRb is inactive or mutated it can no longer act as a regulator.
Usually pRb is hypophosphorylated- bound to E2F.
when CDK binds to cyclin D- the complex phosphorylates pRb which causes it to lose its affinity for EF2- EF2 is a transcription.
Associated with retinoblastoma
What are the main CDK inhibitors
- INK4A which bind to CDK4 and CDK6 e.g. PK16^INK4A
- CIP, KIP
