Oncology and Pathology Flashcards
(29 cards)
Which Tumours like to travel to the bone?
lung
breast
prostate
ovary
Which tumors metastasis to everywhere in the body?
melanoma
kidney
thyroid
Which bones do tumour mainly metastasis to?
Spine!!!,
Pelvis,
Femur,
Humerus,
Ribs,
Skull
What are the names of cancers based on their tissue origin?
Epithelial cells →
Mesoderm cells →
Glandular cells →
Epithelial cells → Carcinomas
Mesoderm cells → Sarcomas
Glandular cells → Adenocarcinomas
What are the exposures/ factors that led to cancer
- Radiation
- Ageing
- Pollution
- Environment
- Diseases (COPD)
- Genetics
- Occupation
- Asbestos
- Tobacco
- second hand smoke
What are Hallmarks of Cancer?
- Avoid immune destruction
- Unlimited replicative potential
- Tumour promoting inflammation
- Invasion and metastasis
- Angiogenesis
- Genome instability and mutation enabling
- Evasion of cell death - limited response to apoptotic signals
- Reprogramming energy metabolism
- Growth signal autonomy - do not need GF signaling to divide
- Evasion of growth inhibitory signals
Explain the normal activation of transmembrane Tyrosine Kinases receptors?
- they are involved in mediating cell-to-cell communication and controlling various biological functions
- they ae activated by receptor-specific ligands - dimerization’s results in down stream transmembrane conformational changes placing the tyrosine kinase in an ‘active’ confirmation
What are the two ways Tyrosine Kinase Receptors can be dysregulated?
- ligand-_dependent_ firing mutating to ligand-_independent_ firing
- receptor remains the same however has autocrine signaling/ activation
What Tyrosine Kinase Growth Factor receptors are altered in human tumours?
-
EGF-R/ErbB1
- overexpression → non-small cell lung cancer, breast, head and neck, stomach, colorectal, esophageal, prostate, bladder, renal, pancreatic and ovarian carcinomas, glioblastomas
- truncation of ectodomain → glioblastoma, lung and breast carcinoma
-
ErbB2/HER2/Neu
- overexpression → 30% of breast adenocarcinomas
-
FGF-R3
- overexpression; amino acid substitutions→ multiple myeloma, bladder and cervical carcinomas
-
Flt-3
- tandem duplication → acute myelogenous leukemia
-
Kit
- amino acid substitution → gastrointestinal stromal tumour
Give examples of receptors making autocrine growth factors and what Human tumours they present in?
- Met: HGF ligand → miscellaneous endocrinal tumours, invasive breast and lung cancers, osteosarcoma
- IGF-1R: IGF-2 ligand → colorectal
- EGF-R: TGF-∝ ligand → squamous cell lung, breast and prostate adenocarcinoma, pancreatic, mesothelioma
- VEGF-R (Flt-1): VEGF-A ligand → neuroblastoma, prostate cancer, Kaposi’s sarcoma
- ErbB2 (HER2 or NEU)/ErbB3: NRG ligand → Ovarian carcinoma
What are the therapeutic options for the following hallmarks of cancer?
what is the treatment strategies in cancers that have an EGFR mutation?
- EGFR- Tyrosine kinase inhibitors - Afatinib
- Anti-EGFR antibody inhibitors
What is a common mechanism of resistance to Tyrosine Kinase Inhibitors?
T790M mutations in the gene that codes for EGFR (epidermal growth factor receptor). This increases the affinity for ATP
- 60% of progressive disease is due to the T790M mutation
How do cancers occur?
- Oncogenesis is a multistage process, cells accumulate damage in several important genes related to mitosis/ cell differentiation
- most mutations acquired in our somatic cells
- some cancers inherited due to mutations in the germline
Give an example of an inherited mutation in an Oncogene
- what does it cause?
RET oncogene (MEN2A - Multiple endocrine neoplasia type 2)
- Parathyroid cancer
- Pheochromocytoma
- Medullary thyroid cancer
Give an overview and epidemiological background of Multiple Endocrine Neoplasia type 2 (MEN2)
- inherited autosomal dominant
- occurs in 1:40,000
- RET proto-oncogene codes for tyrosine kinase receptor
- should be suspected when ≥ 2 endocrine tumour occur together
- 95% of people with genetic variant will present with medullary thyroid cancer
- Pheochromocytoma occurs in 50%
- Hyperparathyroidism in 20-30% of those with the variant
How would a person with MEN2A present clinically?
- Medullary thyroid cancer
- mass or lump in in neck, may be painful
- Cushing syndrome
- facial flushing
- Excess hormone production from
- pheochromocytomas (adrenals)
- High blood pressure
- glucose intolerance
- pallor and vasoconstriction
- and/or adenomas in parathyroid glands
- pheochromocytomas (adrenals)
- with symptoms of these diseases
- bone pain due to metastasis
- weight loss
- severe diarrhea (due to calcitonin and hormones released)
What is the management for Medullary thyroid cancer?
- Total thyroidectomy and neck dissection
- Thyroid hormone replacement
- Tyrosine Kinase inhibitors in metastatic or unresectable cases
What is the management in Phaeochromocytoma?
- Medical treatment of blood pressure
- unilateral adrenalectomy (must be removed before nay other surgery)
What is the management of hyperparathyoidsm
- resect affected gland
- annual screening
What screening tests are available for MEN2A?
- MTC : annual calcitonin, check TFTs, annual neck/thorax imaging
- Phaeo: annual plasma metanephrines, BP, annual abdominal scan
- Primary hyperparathyroidism: annual calcium
- Genetic testing: can detect >95%s of variants in RET gene
- Children of affected individual have 50% chance of inheriting the gene variant
- 95% of MEN2A patients will have an affected parent
Give an example of a Tumour suppressor genes cancer?
- Retinoblastoma - inherited cases more likely to have bilateral disease at younger age compared to sporadic case of RB
What is the aetology and epidemiology of retinoblastoma?
- Majority of cases are related to variants in teh RB1 retinoblastoma gene
- <1% may be due to N-myc amplification
- 10% of children with Rb have a family history
Unilateral Rb cases: genetic variants in both copies of RB1 gene in retina (somatic variants) Variants present in the retinoblastoma tumour tissue & not usually in DNA in blood
Of the 40% tumours that are bilateral: germline mutation in >95% cases
What is the management of retinoblastoma?
- Care led by tertiary service (Birmingham and London)
- Clinical genetic services
- Up to 50% new cases: enucleation (removal of the eye)
- less often if identify families who are gene carriers/at risk & have follow up surveillance
- Local treatment: laser therapy/cryotherapy
- Chemotherapy (systemic or locally)
