PoD - Tumour Pathology Flashcards
1
Q
what is a tumour?
A
- an abnormal growing mass of tissue
- it’s growth is uncoordinated with that of surrounding normal tissue
- it’s growth continues after the removal of any stimulus which may have caused the tumour - capable of autonomous growth
2
Q
what types of tumours are there?
A
- benign (don’t cause any significant or pathological problems - mostly pressure)
- malignant (cancer)
3
Q
what is the definition of cancer?
A
- a fundamental property of cancer is its ability to invade into adjacent tissue and to metastasise and grow at other sites within the body
4
Q
what are metastases?
A
- secondary tumours
- will resemble the primary tumour
- it is harder to treat patients’ cancers that have metastasised - not feasible to surgically remove all of them
5
Q
what are the most common cancers in the UK?
A
- male = prostate
- female = breast
- overall = breast
6
Q
how are tumours classified?
A
- based on tissue of origin (epithelium, connective tissue, blood cells, lymphoid tissues, melanocytes, neural tissue, germ cells)
- benign or malignant
7
Q
how are epithelial tumours named?
A
- 2 broad types of epithelium which tumours can originate from
- any type of malignant epithelium is a CARCINOMA
- glandular
benign = adenoma
malignant = adenocarcinoma - squamous
benign = squamous papilloma
malignant = squamous carcinoma
8
Q
how are connective tissue tumours named?
A
- bone, fat or fibrous tissue
- any type of malignant connective tissue is called a SARCOMA
- bone
benign = osteoma
malignant = osteo-sarcoma - fat
benign = lipoma
malignant = lipo-sarcoma - fibrous tissue
benign = fibroma
malignant = fibro-sarcoma
9
Q
how are blood cell tumours named?
A
- only WBCs can develop a tumour
- there are no benign tumours
malignant
= leukaemia
10
Q
how are tumours of lymphoid tissue named?
A
- there are no benign tumours
malignant
= lymphoma
11
Q
how are tumours of melanocytes named?
A
- benign tumours = naevus
- malignant tumour = melanoma
12
Q
how are neural tissue tumours named?
A
- central nervous system = astrocytoma
peripheral nervous system
= schwannoma
13
Q
what are germ cell tumours called?
A
- tumour composed of various tissues - indicates the pluripotent capability of germ cells = teratomas - develop in ovary/testis - ovarian teratomas = benign - testicular teratomas = malignant
14
Q
list features of malignant tumours
A
- invasive growth pattern
- no capsule/capsule breached by tumour
- cells look abnormal
- cancers poorly differentiated - lack of normal tissue left
- loss of normal function
- metastases
- frequently cause death
15
Q
what is a tumour suppressor gene?
A
- keep cells under regulatory control
- loss of these = tumour formation (normally need to lose both to cause cancer)
- examples = retinoblastoma (RB1), breast cancer (BRCA1)
16
Q
what is an oncogene?
A
- oncogene activates abnormal cell division
e. g B-raf, cyclin D1, erbB2, k-ras
17
Q
what happens to tumour cell links?
A
- loss of cell-cell adhesion (normal cells stick together, but this fails in cancer cells which allows them to invade and spread)
- altered cell-matrix adhesion
- production of tumour biomarkers
18
Q
what are tumour biomarkers useful for?
A
- screening - detecting cancers while still asymptomatic
- diagnosis
- prognostic - identifying a patient’s outcome
- predictive - identifying how patients will respond to a particular therapy
19
Q
list the tumour biomarkers currently used clinically
A
- alpha-fetoprotein
= teratoma of testis
= hepatocellular carcinoma - carcinoma-embryonic antigen (CEA)
= colorectal cancer - oestrogen receptor
= breast cancer - prostate specific antigen
= prostate cancer
20
Q
what are clinically useful predictive tumour markers?
A
- Kras = colorectal c
- Braf = melanoma
- EFGR = lung c
- PD-L1 = lung c
- Her2 = breast/gastric x
21
Q
how do tumours grow?
A
- balance between angiogenesis and apoptosis
- angiogenesis = new blood vessel formation, required to sustain growth via nutrients, O2, also provides a route for metastases
- apoptosis = mechanism of programmed cell death, regulates tumour growth
22
Q
how do tumours spread?
A
- invasion and metastasis
- need to create a track to move through = increased matrix degradation by proteolytic enzymes
- need to be able to move = altered cell-cell/cell-matrix adhesion
23
Q
what happens in tumour invasion?
A
- tumour invasion occurs when adhesion has broken down, allowing invasion into connective tissue the into the lymph/blood vessels
24
Q
what happens in tumour metastasis?
A
- lymphatic metastasis occurs when there is adhesion of tumour cells to lymph vessels, they invade into the lymph node, form metastasis in lymph node
- metastasis via blood = adherence of tumour cells to blood cells, invasion from BVs, invasion into tissue and formation of metastasis
25
Q
where are common sites of metastasis?
A
- liver, lung, brain, bone (axial), adrenal gland
- uncommon = spleen, kidney, skeletal muscle, heart
breast c = bone metastases
prostate c = bone mets
CRC = liver mets
ovary = omentum/peritoneum mets
26
Q
what are the effects of benign and malignant tumours?
A
- benign tumours = pressure and obstruction
- malignant = tissue destruction, bleeding, pain, side effects from tumour
27
Q
can tumours produce hormones?
A
- yes
- they can produce normal hormones for that tissue but abnormal amounts
- they can also have abnormal hormone secretion where the tumour produces hormones not normally produced in that organ i.e ACTH in lung cancer
28
Q
what are paraneoplastic syndromes?
A
- can’t be explained by local or metastatic effects of tumours
i. e neuropathy, myopathy
29
Q
what is dysplasia?
A
- an early sign of cancer
- pre-malignant change
- earliest change in process of malignancy
- characterised by disorganisation of cells
(increased nuclear size, increased mitotic activity, abnormal mitoses) - there is no invasion
30
Q
describe normal cell division
A
- mitosis
- Interphase - cell grows and accumulates nutrients needed for mitosis, RNA is synthesised, produce proteins (irreversible)
- Mitosis - cell splits itself into two distinct cells
- cytokinesis - new cell is completely divided
31
Q
describe the need for cell checkpoints and list key checkpoints
A
- to detect and repair genetic damage and prevent uncontrolled cell division
- checkpoints prevent abnormal cells progressing further in the cycle
- G1/S checkpoint it the KEY restriction point
- cells that progress through this point are committed to S phase and progression is autonomous
- there is also a G2/M checkpoint which stops cells with damaged/incomplete DNA continuing
32
Q
describe cell mutations and where they would arrest in the cycle
A
- inadequate nutrient supply = G1
- external stimuli lacking = G1
- abnormal cell size = G1/S
- DNA not replicated = S
- DNA damage detected = G1/2
- chromosome misalignment = M
33
Q
what are cell cycle checkpoint activators?
A
- system of cyclically in-/active enzyme switches
- Cyclins and cyclin-dependant kinases (CDKs) - determine cells progress through cell cycle
- CDKs are the catalytic subunits but cannot function w/o cyclin
- the active enzyme = CDK/cyclin complex
- active complex phosphorylates target proteins = activates/inactivates target proteins
example
- a pro-mitotic signal induces G1 cyclin-CDK complexes, becomes active and prepare the cell for S phase
34
Q
what are cell cycle inhibitors?
A
- molecules that bind to cyclin-CDK complexes, inhibiting next phase of cell cycle
- INK4a - p16 binds to CDK4 and arrests the cycle in G1 phase
- CIP/KIP genes p21/27/57 halt cell cycle in G1 by inactivating CDK-cyclin complexes
35
Q
how does the retinoblastoma gene regulate the cell cycle?
A
- the Rb gene is ACTIVE when NOT phosphorylated, phosphorylation inactivates enzyme
- in the hypophosphorylated state, pRb carries out it’s role as a tumour suppressor by inhibiting cell-cycle progression
- Active cyclin D-CDK complexes phosphorylate Rb as the cell cycle progresses
- inactive Rb loses affinity for E2F transcription factor which is vital for cells to pass the restriction point (G1/S)
36
Q
what is carcinogenesis?
A
- failure of cell cycle control which results in uncontrolled proliferation of cells - tumour
- the cyclin D-pRb-E2F pathway and p53 pathway are the two most frequently disrupted cell-cycle regulators
37
Q
what does p53 do?
A
- p53 is activated when exposed to DNA-damaging agents
- activation leads to cell cycle arrest in G1 and attempts to repair DNA
- triggers up regulation of the CDK inhibitor p21 and the GADD45 gens (growth arrest & dna damage)
- successful repair of DNA allows cells to continue with cycle
- however, if DNA repair fails - p53 induces apoptosis genes
- in cells with loss/mutated p53, DNA damage doesn’t induce cell-cycle arrest or DNA repair = tumours
38
Q
how can carcinogenesis be induced?
A
- chemical damage
- radiation
- oncogenic viruses
- genetic predisposition
39
Q
describe two-hit hypothesis
A
- suggests that in order to get the cancer, two mutations have to occur
- some individuals may have inherited the first DNA insult, meaning any second insult would rapidly lead to cancer
- in non-inherited (sporadic cases), two mutations would have to occur before a tumour can develop
- explains why individuals with inherited cancers are likely to experience it at a younger age
40
Q
what are tumour suppressor genes?
A
- protect cell from forming cancers
- generally follow the two-hit hypothesis ideal
- loss of both normal alleles gives rise to cancer
- mutation gives rise to loss of function, means cells are able to grow & proliferate without control
examples
= p53, Rb, INK4a
41
Q
list examples of inherited cancer syndromes
A
- familial retinoblastoma
(mutation of RB1 gene) - familial adenomatous polyposis of colon
- hereditary breast & ovarian cancer (mutated BRCA1/2 genes)
- hereditary non-polyposis CRC (mutations in DNA mismatch repair genes)
42
Q
what are oncogenes?
A
- increased function of growth regulating hormones (GFs, signal transducers, cell cycle regulators)
- caused by alteration of porto-oncogene structure (point mutation/translocation) or dysregulation of proto-oncogene expression (gene amplification/over-expression)
43
Q
what are the targets for chemical and radiation carcinogenesis?
A
- purine and pyrimidine bases in DNA
- chemicals oxidise and alkylate the bases = damaging them
44
Q
what occurs in viral carcinogenesis?
A
- virus genome inserts near a host proto-oncogene
- viral promoter causes proto-oncogene over-expression
- virus directly inserts an oncogene into host DNA causing cell division
(HPV - genital cancers)
