Tumour Pathology Flashcards
1
Q
What is a tumour?
A
An abnormal growing mass of tissue
Its growth is uncoordinated with that of surrounding normal tissue
It continues growing even after the removal of any stimulus which may have caused the tumour
2
Q
What is a malignant tumour?
A
Tumours which are able to invade adjacent tissue to metastasise and spread to other sites within the body
3
Q
How do we classify tumours?
A
Tissue of origin
Whether it is benign or malignant
4
Q
What is an adenoma?
A
A benign tumour found in glandular epithelium tissue
5
Q
What is a squamous papilloma?
A
A benign tumour found in squamous epithelium tissue
6
Q
What is an adenocarcinoma?
A
A malignant tumour found in glandular epithelium tissue
7
Q
What is an squamous-carcinoma?
A
A malignant tumour found in squamous epithelium tissue
8
Q
What is an osteoma?
A
A benign tumour found in the connective tissue of bone
9
Q
What is a lipoma?
A
A benign tumour found in the connective tissue of fat
10
Q
What is a fibroma?
A
A benign tumour found in the connective tissue of fibrous tissue
11
Q
What is an osteo-sarcoma?
A
A malignant tumour found in the connective tissue of bone
12
Q
What is a lipo-sarcoma?
A
A malignant tumour found in the connective tissue of fat
13
Q
What is a fibre-sarcoma?
A
A malignant tumour found in the connective tissue of fibrous tissue
14
Q
What is leukaemia?
A
A malignant tumour associated with white blood cells
15
Q
What is a lymphoma?
A
A malignant tumour found in the lymphoid tissue
16
Q
What is a melanoma?
A
A malignant tumour associated with melanocytes
17
Q
What is a naevus?
A
A benign tumour associated with melanocytes
18
Q
What is a astrocytoma?
A
A malignant tumour found in neural tissue of the CNS
19
Q
What is schwannoma?
A
A malignant tumour found in neural tissue of the PNS
20
Q
What is an ovarian teratoma?
A
A benign tumour found in the ovaries
21
Q
What is a testicular teratoma?
A
A malignant tumour found in the testis
22
Q
What growth pattern are seen in benign and malignant tumours?
A
Benign - non-invasive
Malignant - invasive
23
Q
Is there a capsule present in benign and malignant tumours?
A
Benign - usually encapsulated
Malignant - no capsule or capsule breached by tumour cells
24
Q
Is there evidence of invasion in benign and malignant tumours?
A
Benign - no
Malignant - yes
25
Is there a presence of metastases in benign and malignant tumours?
Benign - no
Malignant - yes
26
How are the cells differentiated in benign and malignant tumours?
Benign - well
Malignant - poorly
27
How do the cells appear in benign and malignant tumours compared to normal cells?
Benign - similar
Malignant - abnormal
28
How do the cells function in benign and malignant tumours compared to normal cells?
Benign - similar
Malignant - loss of function
29
Do benign or malignant tumours cause death?
Benign - rarely, only if it develops near the brain, heart or major blood vessels
Malignant - frequently
30
What are the six properties of of cancer cells?
Loss of tumour suppressor genes
Gain of function in oncogenes
Altered cellular function - cells lose their ability to adhere to one another and to adhere to the matrix (underlying cells).
Abnormal morphology (appearance)
Cells capable of independent growth
Tumour biomarkers present - proteins expressed in tumours
31
What is tumour angiogenesis?Why is it essential?
The process used to describe new blood vessel formation by tumours.
Allows nutrients to access tumours which are required to sustain tumour growth
Provides a route of release of tumour cells into circulation
32
Why does increased tumour angiogenesis result in a poorer prognosis?
Higher chance the tumour cells to get into the blood vessels and form secondary tumours in other sites
33
What are tumour biomarkers used for clinically?
To screen and diagnose cancers
Predict a patient's prognosis
Select the most appropriate therapy
34
What are the four groups of biomarkers?
Onco-fetal proteins
Oncogenes
Growth factors and receptors
Immune checkpoint inhibitors
35
What two cancers does an alpha-fetoprotein biomarker associate with?
Teratoma of the testis
Hepatocellular carcinoma
36
What cancer does a carcinogen-embryonic antigen (CEA) biomarker associate with?
Colorectal cancer
37
What cancer does an oestrogen biomarker associate with?
Breast cancer
38
What cancer does a prostate specific antigen biomarker associate with?
Prostate cancer
39
What two processes are involved in the spread of cancer?
Invasion
Metastasis
40
What is involved in tumour invasion?
Tumour invades surrounding connective tissue it does this by releasing proteolytic enzymes which alters cell-cell and cell-matrix adhesions.
From the connective tissue, the tumour can then invade the lymph and blood vessels
41
What is involved in tumour metastasis?
The tumour invades the blood or lymph vessels.
If they invade the lymph vessels, the tumour cells invade the lymph nodes. They form secondary tumours in these nodes.
If they invade the blood vessels, the tumour cells invade tissue. They form secondary tumours in these tissues
42
What are the four methods in which cancerous cells can spread?
Local spread
Lymphatic spread
Blood spread
Trans-coelomic spread
43
What is trans-coelomic spread?
Form of local spread, where the tumour cells spread across body cavities. This type of spread results in multiple tumours developing quite rapidly.
44
What are tumour spread sites dependent on?
Metastatic niche - whether the environment will support tumour growth or not
45
What are the common sites of metastasis?
Liver
Lung
Brain
Axial Skeleton Bone
Adrenal Gland
Omentum/Peritoneum
46
What are the uncommon sites of metastasis?
Spleen
Kidney
Skeletal Muscle
Heart
47
Where do breast tumours tend to spread to?
Bone
48
Where do prostate tumours tend to spread to?
Bone
49
Where do colorectal tumours tend to spread to?
Liver
50
Where do ovary tumours tend to spread to?
Momentum/Peritoneum
51
What are the local effects of benign tumours?
Pressure from surrounding tissues
Obstruction of surrounding tissues
52
What are the local effects of malignant tumours?
Pressure from surrounding tissues
Obstruction of surrounding tissues
Tissue destruction
Bleeding - due to tumour being near a large blood vessel, which can cause haemorrhage
Pain - due to tumour applying pressure on nerves
Effects of treatment
53
What are the systemic effects of malignant tumours?
Weight loss-cancer cachexia - unexplained weight loss
Secretion of hormones
Paraneoplastic syndrome - muscle, pain nerve pain and muscle weakness
Effects of treatment
54
What is normal secretion of hormones by tumours?
When tumours of an endocrine organ produce an abnormal amount of its normal hormone
55
What is abnormal secretion of hormones by tumours?
When tumours produce a hormone from an organ that does mot usually produce hormones
56
Which two hormones are secreted abnormally? Which cancer are they related to?
ACTH and ADH
Lung cancer
57
What is dysplasia?
The pre-invasive stage, also defined as the pre-malignant change
It is the earliest change in the process of malignancy that can be visualised
58
Where is dysplasia normally visualised?
In the epithelium
59
What are the two common features of dysplasia?
Disorganisation of cells
No invasion
60
What does a high grade of dysplasia mean?
The higher the degree of abnormality
61
How are dysplastic cells commonly identified?
Through cancer screening tests
62
What does cell division allow?
Cell to grow and develop
Replace dead tissue
Repair tissue
63
What is the product of the cell cycle?
Two genetically identical daughter cells
64
What are the three phases of the cell cycle?
Interphase
Mitosis
Cytokinesis
65
What are the three phases of interphase?
G1
S
G2
66
Why is it important that the cell cycle is controlled?
Cell requires sufficient nutrients and growth factors to be present before it moves on to the next stage
Ensures each daughter cell receives the full chromosome complement
Detect and repair and damage that occurs during the cell cycle
67
What occurs if the rate of the cell cycle is reduced?
Degenerative diseases, as tissues are unable to function properly
68
What occurs if the rate of the cell cycle is increased?
Tumour formation
69
Where are the three checkpoints in the cell cycle?
End of G1
End of G2
Middle of M - metaphase step
70
What is the role of the G1 checkpoint?
Checks whether there is the correct number of organelles
Checks cell size
Checks the external stimulus
Checks nutrient supply
Check for DNA damage
71
What is the rate-limiting step in the cell cycle? Why?
G1/S transition step
Cells that progress through this point are committed to enter the S phase.
72
What happens when a go-ahead signal is not reached at the G1 checkpoint?
Cell switches to a non-diving state known as G0.
In G0, no cyclin proteins are produced which means it has left the cell cycle
Functions as a differentiated cell, just resting
73
What is the role of the G2 checkpoint?
Checks cell size
Check external stimulus
Checks the success of DNA replication - as there is no checkpoint during S, ensures each daughter cell will receive a complete copy of DNA
74
What happens if a cell passes the G2 checkpoint?
Start of mitosis is triggered by a complex called the mitosis promoting factor (MPF)
75
What happens if a cell fails the G2 checkpoint?
Apoptosis
76
What is the role of the metaphase checkpoint?
Checks chromosome alignment - to ensure each daughter cell received one chromatid from each chronometer
To ensure spindle formation was successful
77
What happens if a cell passes the M checkpoint?
It proceeds to anaphase
78
What happens if a cell fails the M checkpoint?
Apoptosis
79
What regulatory molecules determines a cell's progress through the cell cycle? How?
Cyclins & CDKs
During G1, the cyclin proteins accumulate and combine with the CDKs to produce MPF and active CDK/cyclin complexes
Active CDK/cyclin complexes cause the phosphorylation of proteins that stimulate the cell cycle.
If a sufficient threshold of phosphorylation is reached, the checkpoint is passed and the cell moves onto the S phase
If an insufficient threshold of phosphorylation is reached, the cell is held at the checkpoint
80
What happens to a cell if there are no active CDK/cyclin complexes?
Enter G0
81
Why are different cyclins used for each phase of the cell cycle?
Cell won't skip any checkpoints
Allows the processes to occur at the right time and ensures they are complete before they move on
82
What are CDK inhibitors?
Molecules that bind to the CDK/cyclin complexes and inhibit them, preventing them from phosphorylating their target proteins and the cll moving on to the next phase
83
Name two CDK inhibitors
INK4A gene family
CIP/KIP gene family
84
What CDK does p16INK4A inhibit and at what phase?
CDK4
G1
85
What phase do CIP/KIP gene families inhibit CDK/cyclin complexes?
G1
86
What regulatory protein determines a cell's progress through the cell cycle? How?
Retinoblastoma protein (Rb). It is one of the proteins phosphorylated by active CDKs.
This protein is a transcription-factor inhibitor and is involved in the regulation of proteins that are required for DNA replication in the S phase.
Hypo-phosphorylated form of Rb restricts progression from G1 to S. This is because the Rb protein is active and acts as a clamp on the transcription factor E2F, which means that proteins needed for the S phase cannot be synthesised
However, when CDKs phosphorylate the Rb protein, it results in the inhibition of Rb, meaning that it becomes inactive and can no longer bind to the transcription of E2F, which allows the transcription of proteins needed for S.
87
What is carcinogenesis? Why does it occur?
Failure of cell cycle control that results in tumour formation
Failure of control is due to mutation occurring in genes that regulate cell division, apoptosis and DNA repair
Commonly mutations in the cyclin, CDKs, Rb and p53 pathways
88
When is DNA repair likely to occur after DNA damage?
When a minor mutation has occurred that only affects one amino acid
89
When is apoptosis likely to occur after DNA damage?
When a major mutation has occurred that affects multiple amino acid
90
What protein is activated when DNA is damaged?
p53
91
What three things does p53 do when it is activated?
Activate DNA repair proteins to repair the DNA damage
It can arrest the cell cycle at the G1 checkpoint, this allows DNA repair proteins to repair the damage so that the cell cycle can be restarted
It can initiate apoptosis
92
What three proteins repair DNA?
CDKI
p21
GADD45
93
What are environmental factors that cause carcinogenesis called?
Genotoxins
94
What is the two hit hypothesis?
Explains that multiple hits to DNA are required for cancer to develop
95
How does the two hit hypothesis explain why cancer can be genetically inherited?
In children, with inherited cancer, the first DNA insult was inherited. Any second insult would rapidly lead to cancer. This second insult is a somatic point mutation of the other copy
In the non-inherited form of cancer, two hits have to take place in a single cell before a tumour develops, explaining why it occurs later on in life
96
What is the role of tumour suppressor genes?
Regulate the cell cycle and apoptosis.
97
What three genes are regulated by tumour suppressor genes? What processes are these genes involved in?
Rb - cell cycle
INK4A family - cell cycle
p53 - apoptosis and repair
98
What hypothesis do tumour suppressor genes follow? What does this mean?
Two hit hypothesis
Recessive alleles, which means that loss of both normal copies give rise to cancer
99
What genes may be inherited by an individual that results in them having a predisposition to developing cancer?
Tumour supressor genes
Mismatch repair genes
Protoncogenes
100
What cancers are commonly genetically transmitted?
Breast
Colorectal
Gynaecological
Endocrine
Retinoblastoma
Familial adenomatous of colon
101
What are proto-oncogenes?
Normal genes coding for normal growth of regulating proteins
102
What are oncogenes?
Derived from proto-oncogenes but have an additional function.
103
What are the two ways that oncogenes can be activated?
They are activated by alteration of the proto-oncogene structure, due to a mutation.
They can also be activated by dysregulation of proto-oncogene expression, due to gene amplification or over-expression.
104
How do chemical carcinogens cause cancer?
React with DNA to form covalently bound products, which are known as DNA adducts.
DNA adducts lead to the activation of oncogenes and loss of tumour suppressor genes
105
How do radiation carcinogens cause cancer?
Direct DNA damage can occur when DNA directly absorbs a photon of UV radiation. This causes T base pairs next to each other to bind together and form dimers. These dimers disrupt the strand, which means it cannot be replicated
106
How do viral carcinogens cause cancer?
Carry a gene that encodes for an overactive oncogene, called viral-oncogene.
107
What three viruses are known to cause cancer?
HPV
Hepatitis B
EBV
108
What cancer does HPV cause?
Cervical
109
What cancer does EBV cause?
Lymphoma
110
What cancer does Hep B cause?
Liver
111
What cancer does the Kras biomarker relate to?
Colorectal
112
What cancer does the Braf biomarker relate to?
Melanoma
113
What cancer does the EGFR biomarker relate to?
Lung
114
What cancer does the PDL-1 biomarker relate to?
Lung
115
What cancer does the Her-2 biomarker relate to?
Breast + gastric
116
Where does breast cancer commonly metastasise to?
Bone
117
Where does prostate cancer commonly metastasise to?
Bone
118
Where does colorectal cancer commonly metastasise to?
Liver
119
Where does ovary cancer commonly metastasise to?
Ometum/peritoneum
