Neoplasia Flashcards
Contrast the general features of benign vs malignant tumours
Benign: locally expansile, slow growth, often well circumscribed (+/- capsule), well differentiated cells, unable to metastasise
Malignant: locally invasive, often poorly circumscribed, can be necrotic, variable differentiation, potential to metastasise
What are the 3 main modes of metastasis?
Lymphatic
Haematogenous
Transcoelomic (through membranes)
List 8 histopathological features of neoplasia
Large nuclei Pleomorphic nuclei (vary in size and shape) Coarser nuclear chromatin Hyperchromatic nuclei Prominent nucleoli Abnormal mitotic figures Architectural disorganisation Desmoplastic stroma
What are anaplastic cells?
Completely undifferentiated cells
What prefix is used for a glandular tumour?
Adeno
What prefix is used for a smooth muscle tumour?
Leiomyo
What prefix is used for a osteoblastic (osteoid-forming) tumour?
Osteo
What suffix is used for a benign tumour?
-oma (there are some exceptions to this, e.g. lymphoma)
What suffix is used for a malignant epithelial tumour?
Carcinoma
What suffix is used for a malignant mesenchymal tumour?
Sarcoma
What are 2 characteristic histological features of glandular tumours?
Formation of glandular lumina
Signet ring cells producing mucin
What are 3 characteristic histological features of squamous cell tumours?
Eosinophilic cytoplasm
Keratinisation
Intercellular bridges
What does tumour grade measure?
Degree of differentiation
What is an in situ carcinoma?
Generally refers to severe (grade 3) dysplasia
How do neoplasms invade past the basement membrane?
Can degrade the BM via release of matrix metalloproteinases
When are polyps commonly formed?
When glandular dysplastic lesions occur in epithelia lining organs
What are the 4 classes of normal regulatory genes relevant to carcinogenesis?
Growth-promoting proto-oncogenes
Growth-inhibiting TSGs
Genes regulating apoptosis
DNA repair genes
Give 3 examples of TSGs
p53
Rb
APC
Give 3 examples of oncogenes
HER2
Ras
Myc
Given an example of a DNA repair gene
BRCA (1, 2)
What is the difference between a mutation and a polymorphism in cancer genetics?
Mutation: any change in a DNA sequence away from normal (implies there is a normal allele that is prevalent in the population), involved in pathogenesis of cancer
Polymorphism: DNA sequence variation common in the population (no single allele is considered standard), influences RISK of cancer
What is responsible for the slow progression in low growth fraction tumours?
Cell production vs. death occurs at a similar rate
Give 3 examples of high growth fraction tumours
Leukaemias
Lymphomas
Small-cell carcinoma
Give 2 examples of low growth fraction tumours
Colon
Breast adenocarcinoma
What are oncogenes?
Mutant versions of proto-oncogenes that function autonomously without a requirement for normal growth-promoting signals
Give 5 examples of common (normal physiological) roles of oncogenes
Growth factors (acting in autocrine manner) Growth factor receptors Signal transduction proteins TFs Cyclins and CDKs
What is loss of heterozygosity (LOH)?
Loss of normal function of 1 allele of a gene in which the other allele was already inactivated
What is p53 and what is its role?
TF which can regulate the expression of cell cycle factors
Involved in apoptosis, cell-cycle arrest, DNA repair, differentiation and senescence
What are some of the mechanisms regulating TSG expression?
miRNA-mediated control
Epigenetic control
What are 6 mechanisms used by neoplasms to evade apoptosis?
IMAGE
Reduced CD95 level
Inactivation of death-induced signalling complex by FLICE protein
Upregulation of anti-apoptotic Bcl-2
Reduced levels of pro-apoptotic BAX resulting from loss of p53
Loss of APAF-1
Upregulation of inhibitors of BAX
How do tumour cells develop immortality?
Via reactivation of telomerase
What is the molecular mechanism underlying metastasis?
Detachment: via disruption of cellular “glue” (cadherins, beta-catenin, connexins)
Degradation of ECM
Attachment to novel ECM components
Migration of tumour cells
What are some popular therapeutic targets for cancer and what is the role of these targets?
VEGFs, VEGF receptors
Involved in tumour angiogenesis
List 10 characteristics of tumours and the classes of therapeutics used to target them
Sustaining proliferative signalling: EGFR inhibitors
Evading growth suppressors: CDK inhibitors
Avoiding immune destruction: immune-activating anti-CTLA4 mAb
Enabling replicative immortality: telomerase inhibitors
Tumour-promoting inflammation: selective anti-inflammatory drugs
Activating invasion and metastasis: inhibitors of HGF/c-Met
Inducing angiogenesis: inhibitors of VEGF signalling
Genome instability and mutation: PARP inhibitors
Resisting cell death: pro-apoptotic BH3 mimetics
Deregulating cellular energetics: aerobic glycolysis inhibitors
What causes weight loss and anorexia in cancer?
TNF-a, IL-1 produced by tumour cells or cells in the tumour microenvironment
What are the 4 important diagnostic/prognostic factors to determine following a diagnosis of malignancy?
Specific tumour type and subtype (cell lineage)
Grade
Stage
Presence of lymphovascular invasion
What does tumour stage measure?
Refers to the progression the malignancy has made in terms of local spread and metastasis
What is the most common staging system used?
TNM
What are the criteria of the TNM staging system?
T: extent of primary tumour (T0-T4 indicating size and local extent)
N: regional LN metastases (N0-N3)
M: absence or presence of distant metastases (M0-M1)
X indicates cannot be assessed or unknown
Components are combined to give a stag grouping, usually from I-IV
What are some prognostic factors in cancer?
Vascular invasion seen in primary tumour
Specific genetic alterations
What are the 2 main categories of targeted therapies for cancer?
Small molecules that e.g. inhibit GF receptors or TK
Monoclonal antibodies that target specific proteins or receptors
When does metaplasia arise?
Response to chronic injury (e.g. GORD, chronic gastritis, chronic inflammation, smoking)
Can be physiological (e.g. cervical transformation zone)
