T5 Behaviour of tumours/ovarian tumours/carcinogenesis Flashcards
main difference between invasion & metastasis
invasion: local
metastasis: systemic
in what way do epithelial cells become similar mesenchymal during cancer?
ability to migrate & invade
epithelial-mesenchyma transition
a mutation in what molecule decreases the cell-cell adhesion?
E-cadherin
changes in the expression of what molecule leads to decreased cell-matrix adhesion?
intigrins
what are the most important proteolytic enzymes in neoplastic invasion? what are they secreted by and what is their function?
- matrix metalloproteinases
- malignant neoplastic cells
- digest surrounding connective tissue
which molecules do interstitial collagenases (metalloproteinases) degrade?
- types 1, 2, 3 collagen
which molecules do gelatinases (metalloproteinases) degrade?
- type 4 collagen
- gelatin
what molecules do stromelysins (metalloproteinases) degrade?
- type 4 collagen
- proteoglycans
most commonly invaded tissues and why?
- blood vessels/nerves
- least resistance
what is the most common route of metastasis initially for carcinoma?
lymphatics
what is the most common route of metastasis for sarcomas?
haematogenous
which organs are most commonly involved in harmatogenous metastasis?
- liver
- lungs
- bones
- brain
where do haematogenous bone metastasis most frequently come from?
- lung
- breast
- kidney
- thyroid
- prostate
which route of metastasis leads to tumour spreading across the peritoneal/pleural cavity?
transcoelomic
what does transcoelomic metastasis lead to? give an example
- effusion containing neoplastic cells
- ovarian cancer
give an example of implantation
- spillage of tumour - surgery
what molecule do cancer cells express to promote new vessel sprouting &angiogeneis?
vascular endothelial growth factor (VEGF)
staging
extent of tumour spread
grading
aggressiveness of tumour
what does TNM stand for in TNM grading system?
T(0-4)- extent of tumour spread
N(0-3)- extent of nodal spread
M(0-1)- presence/absence of distant metastases
staging of lymphoma
- stage 1-4 (spread of lymphoma)
- A-B (symptoms present or not)
from well to poorly differentiated tumours, how does the grades change?
- low grade –> high grade
what is pleomorphism in cancer?
variation in cell size & shape
what are the most common types of ovarian surface epithelial tumours (all glandular epithelia)
- serous (tubal mucosa)
- mucinous (endocervical)
- endometrioid (endometrium)
where do ovarian germ cell tumours arise from
oocyte
where do ovarian sex-cord stroma arise from
sex cord stroma
name a substance that’s used as a marker in ovarian cancer, complex cysts
CA125
benign glandular fibrous epithelial tumour composed of cysts
cystadenofibroma
protective factors of ovarian cancer
- having children
- brestfeeding
- COCP
give an example of teratoma
mature cystic teratoma
(3 elements of germ cell layers) `
teratoma is an example of which type of ovarian tumours? give other examples with their markers
germ cell tumours: - yolk sac tumours - a-FP - embryonal carcinoma - dysgerminomas - LDH - choriiocarcinoma - bHCG (all malignant)
where do teratomas arise from
oocyte that’s completed 1st mitotic division
two features of sex cord stromal tumours
- rare
- produce steroid
which sex cord tumour produce estradiol
- thecomas
- fibrothecomas
- granulosa cell tumours
rank sex cord tumours from most to least malignant
sertoli-leydig –> granulosa –> thecoma/fibrothecoma/fibroma
describe Meig’s syndrome in thecoma/fibrothecoma/fibroma?
triad: ovarian tumour; right sided pleural effusion; ascites
what steroid do sertoli-leydig tumours produce?
androgens
how do metastatic ovarian tumours spread?
- direct
- lymphatic
- haematogenous
origins of metastatic ovarian tumour
- colon
- stomach (krukenberg)
- breast
- uterus
- fallopian
- pelvic peritoneum
description of Krukenberg tumour
- bilateral
- mucin
in the tumour’s sustaining proliferative signalling, what cell surface receptors do growth factors bind to
intracellular tyrosine kinase
which protein do -ve GFs inhibit? what is the function of that protein?
- Rb protein
- regulator of cell cycle - prevents G1–>S phase
how do tumours increase the rate of cell division
- inactivating Rb gene
- resistance to -ve growth regulation
how do tumour cells avoid immune destruction
binding of PD-1 (T cell) & PD-L1 (tumour cell) inhibit T cell activity
how do tumour cells enable replicative immortality
telomere shortening
how can UV cause DNA damage leading to genome instability
- single stranded break
- double stranded break
what substances do tumours release to resist cell death
- Bcl2
- BclXL
what is the name of deregulated metabolism caused by tumour cells
Warburg effect
oncogenes
- mutated version/ increased expression of protogenes
- cause uncontrolled activity
TSG function and genetic pattern for disease
- control genome stability
- recessive
Proto-oncogenes function & genetic pattern for disease
- encode protein involved in control of cell proliferation
- dominant
oncogenes vs TSG
look up weekly summary notes
mechanisms of oncogene activation
- translocation
- point mutation
- amplification
- insertion
tumour supressor genes
- APC
- P53
- RB
- BRCA1 BRCA2
- hMLH1, hMSH2
2 categories of TSGs
- anti-oncogenes - gatekeepers: -ve regulators of cell cycle; +ve regulators of apoptosis
- caretakers: maintain genetic stability
how can carcinogens induce molecular abnormalities in TSGs through epigenetic silencing
- shutdown of gene expression
- methylation of CpG sequences in promoter genes
TSG & familial cancer syndrome
see summary notes
serum markers used for diagnosis
- AFP
- CA125
- hCG
- PSA
serum markers used for monitoring
- CEA
- thyroglobulin
