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Year One - Principles of Disease > Tumour Pathology > Flashcards

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

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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

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3
Q

How do we classify tumours?

A

Tissue of origin

Whether it is benign or malignant

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4
Q

What is an adenoma?

A

A benign tumour found in glandular epithelium tissue

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5
Q

What is a squamous papilloma?

A

A benign tumour found in squamous epithelium tissue

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6
Q

What is an adenocarcinoma?

A

A malignant tumour found in glandular epithelium tissue

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7
Q

What is an squamous-carcinoma?

A

A malignant tumour found in squamous epithelium tissue

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8
Q

What is an osteoma?

A

A benign tumour found in the connective tissue of bone

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9
Q

What is a lipoma?

A

A benign tumour found in the connective tissue of fat

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10
Q

What is a fibroma?

A

A benign tumour found in the connective tissue of fibrous tissue

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11
Q

What is an osteo-sarcoma?

A

A malignant tumour found in the connective tissue of bone

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12
Q

What is a lipo-sarcoma?

A

A malignant tumour found in the connective tissue of fat

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13
Q

What is a fibre-sarcoma?

A

A malignant tumour found in the connective tissue of fibrous tissue

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14
Q

What is leukaemia?

A

A malignant tumour associated with white blood cells

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15
Q

What is a lymphoma?

A

A malignant tumour found in the lymphoid tissue

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16
Q

What is a melanoma?

A

A malignant tumour associated with melanocytes

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17
Q

What is a naevus?

A

A benign tumour associated with melanocytes

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18
Q

What is a astrocytoma?

A

A malignant tumour found in neural tissue of the CNS

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19
Q

What is schwannoma?

A

A malignant tumour found in neural tissue of the PNS

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20
Q

What is an ovarian teratoma?

A

A benign tumour found in the ovaries

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21
Q

What is a testicular teratoma?

A

A malignant tumour found in the testis

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22
Q

What growth pattern are seen in benign and malignant tumours?

A

Benign - non-invasive

Malignant - invasive

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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

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24
Q

Is there evidence of invasion in benign and malignant tumours?

A

Benign - no

Malignant - yes

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25
Q

Is there a presence of metastases in benign and malignant tumours?

A

Benign - no

Malignant - yes

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26
Q

How are the cells differentiated in benign and malignant tumours?

A

Benign - well

Malignant - poorly

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27
Q

How do the cells appear in benign and malignant tumours compared to normal cells?

A

Benign - similar

Malignant - abnormal

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28
Q

How do the cells function in benign and malignant tumours compared to normal cells?

A

Benign - similar

Malignant - loss of function

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29
Q

Do benign or malignant tumours cause death?

A

Benign - rarely, only if it develops near the brain, heart or major blood vessels

Malignant - frequently

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30
Q

What are the six properties of of cancer cells?

A

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

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31
Q

What is tumour angiogenesis?Why is it essential?

A

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

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32
Q

Why does increased tumour angiogenesis result in a poorer prognosis?

A

Higher chance the tumour cells to get into the blood vessels and form secondary tumours in other sites

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33
Q

What are tumour biomarkers used for clinically?

A

To screen and diagnose cancers

Predict a patient’s prognosis

Select the most appropriate therapy

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34
Q

What are the four groups of biomarkers?

A

Onco-fetal proteins

Oncogenes

Growth factors and receptors

Immune checkpoint inhibitors

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35
Q

What two cancers does an alpha-fetoprotein biomarker associate with?

A

Teratoma of the testis

Hepatocellular carcinoma

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36
Q

What cancer does a carcinogen-embryonic antigen (CEA) biomarker associate with?

A

Colorectal cancer

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37
Q

What cancer does an oestrogen biomarker associate with?

A

Breast cancer

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38
Q

What cancer does a prostate specific antigen biomarker associate with?

A

Prostate cancer

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39
Q

What two processes are involved in the spread of cancer?

A

Invasion

Metastasis

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40
Q

What is involved in tumour invasion?

A

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

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41
Q

What is involved in tumour metastasis?

A

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

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42
Q

What are the four methods in which cancerous cells can spread?

A

Local spread

Lymphatic spread

Blood spread

Trans-coelomic spread

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43
Q

What is trans-coelomic spread?

A

Form of local spread, where the tumour cells spread across body cavities. This type of spread results in multiple tumours developing quite rapidly.

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44
Q

What are tumour spread sites dependent on?

A

Metastatic niche - whether the environment will support tumour growth or not

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45
Q

What are the common sites of metastasis?

A

Liver

Lung

Brain

Axial Skeleton Bone

Adrenal Gland

Omentum/Peritoneum

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46
Q

What are the uncommon sites of metastasis?

A

Spleen

Kidney

Skeletal Muscle

Heart

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47
Q

Where do breast tumours tend to spread to?

A

Bone

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48
Q

Where do prostate tumours tend to spread to?

A

Bone

49
Q

Where do colorectal tumours tend to spread to?

A

Liver

50
Q

Where do ovary tumours tend to spread to?

A

Momentum/Peritoneum

51
Q

What are the local effects of benign tumours?

A

Pressure from surrounding tissues

Obstruction of surrounding tissues

52
Q

What are the local effects of malignant tumours?

A

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
Q

What are the systemic effects of malignant tumours?

A

Weight loss-cancer cachexia - unexplained weight loss

Secretion of hormones

Paraneoplastic syndrome - muscle, pain nerve pain and muscle weakness

Effects of treatment

54
Q

What is normal secretion of hormones by tumours?

A

When tumours of an endocrine organ produce an abnormal amount of its normal hormone

55
Q

What is abnormal secretion of hormones by tumours?

A

When tumours produce a hormone from an organ that does mot usually produce hormones

56
Q

Which two hormones are secreted abnormally? Which cancer are they related to?

A

ACTH and ADH

Lung cancer

57
Q

What is dysplasia?

A

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
Q

Where is dysplasia normally visualised?

A

In the epithelium

59
Q

What are the two common features of dysplasia?

A

Disorganisation of cells

No invasion

60
Q

What does a high grade of dysplasia mean?

A

The higher the degree of abnormality

61
Q

How are dysplastic cells commonly identified?

A

Through cancer screening tests

62
Q

What does cell division allow?

A

Cell to grow and develop

Replace dead tissue

Repair tissue

63
Q

What is the product of the cell cycle?

A

Two genetically identical daughter cells

64
Q

What are the three phases of the cell cycle?

A

Interphase

Mitosis

Cytokinesis

65
Q

What are the three phases of interphase?

A

G1

S

G2

66
Q

Why is it important that the cell cycle is controlled?

A

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
Q

What occurs if the rate of the cell cycle is reduced?

A

Degenerative diseases, as tissues are unable to function properly

68
Q

What occurs if the rate of the cell cycle is increased?

A

Tumour formation

69
Q

Where are the three checkpoints in the cell cycle?

A

End of G1

End of G2

Middle of M - metaphase step

70
Q

What is the role of the G1 checkpoint?

A

Checks whether there is the correct number of organelles

Checks cell size

Checks the external stimulus

Checks nutrient supply

Check for DNA damage

71
Q

What is the rate-limiting step in the cell cycle? Why?

A

G1/S transition step

Cells that progress through this point are committed to enter the S phase.

72
Q

What happens when a go-ahead signal is not reached at the G1 checkpoint?

A

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
Q

What is the role of the G2 checkpoint?

A

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
Q

What happens if a cell passes the G2 checkpoint?

A

Start of mitosis is triggered by a complex called the mitosis promoting factor (MPF)

75
Q

What happens if a cell fails the G2 checkpoint?

A

Apoptosis

76
Q

What is the role of the metaphase checkpoint?

A

Checks chromosome alignment - to ensure each daughter cell received one chromatid from each chronometer

To ensure spindle formation was successful

77
Q

What happens if a cell passes the M checkpoint?

A

It proceeds to anaphase

78
Q

What happens if a cell fails the M checkpoint?

A

Apoptosis

79
Q

What regulatory molecules determines a cell’s progress through the cell cycle? How?

A

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
Q

What happens to a cell if there are no active CDK/cyclin complexes?

A

Enter G0

81
Q

Why are different cyclins used for each phase of the cell cycle?

A

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
Q

What are CDK inhibitors?

A

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
Q

Name two CDK inhibitors

A

INK4A gene family

CIP/KIP gene family

84
Q

What CDK does p16INK4A inhibit and at what phase?

A

CDK4

G1

85
Q

What phase do CIP/KIP gene families inhibit CDK/cyclin complexes?

A

G1

86
Q

What regulatory protein determines a cell’s progress through the cell cycle? How?

A

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
Q

What is carcinogenesis? Why does it occur?

A

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
Q

When is DNA repair likely to occur after DNA damage?

A

When a minor mutation has occurred that only affects one amino acid

89
Q

When is apoptosis likely to occur after DNA damage?

A

When a major mutation has occurred that affects multiple amino acid

90
Q

What protein is activated when DNA is damaged?

A

p53

91
Q

What three things does p53 do when it is activated?

A

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
Q

What three proteins repair DNA?

A

CDKI

p21

GADD45

93
Q

What are environmental factors that cause carcinogenesis called?

A

Genotoxins

94
Q

What is the two hit hypothesis?

A

Explains that multiple hits to DNA are required for cancer to develop

95
Q

How does the two hit hypothesis explain why cancer can be genetically inherited?

A

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
Q

What is the role of tumour suppressor genes?

A

Regulate the cell cycle and apoptosis.

97
Q

What three genes are regulated by tumour suppressor genes? What processes are these genes involved in?

A

Rb - cell cycle

INK4A family - cell cycle

p53 - apoptosis and repair

98
Q

What hypothesis do tumour suppressor genes follow? What does this mean?

A

Two hit hypothesis

Recessive alleles, which means that loss of both normal copies give rise to cancer

99
Q

What genes may be inherited by an individual that results in them having a predisposition to developing cancer?

A

Tumour supressor genes

Mismatch repair genes

Protoncogenes

100
Q

What cancers are commonly genetically transmitted?

A

Breast

Colorectal

Gynaecological

Endocrine

Retinoblastoma

Familial adenomatous of colon

101
Q

What are proto-oncogenes?

A

Normal genes coding for normal growth of regulating proteins

102
Q

What are oncogenes?

A

Derived from proto-oncogenes but have an additional function.

103
Q

What are the two ways that oncogenes can be activated?

A

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
Q

How do chemical carcinogens cause cancer?

A

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
Q

How do radiation carcinogens cause cancer?

A

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
Q

How do viral carcinogens cause cancer?

A

Carry a gene that encodes for an overactive oncogene, called viral-oncogene.

107
Q

What three viruses are known to cause cancer?

A

HPV

Hepatitis B

EBV

108
Q

What cancer does HPV cause?

A

Cervical

109
Q

What cancer does EBV cause?

A

Lymphoma

110
Q

What cancer does Hep B cause?

A

Liver

111
Q

What cancer does the Kras biomarker relate to?

A

Colorectal

112
Q

What cancer does the Braf biomarker relate to?

A

Melanoma

113
Q

What cancer does the EGFR biomarker relate to?

A

Lung

114
Q

What cancer does the PDL-1 biomarker relate to?

A

Lung

115
Q

What cancer does the Her-2 biomarker relate to?

A

Breast + gastric

116
Q

Where does breast cancer commonly metastasise to?

A

Bone

117
Q

Where does prostate cancer commonly metastasise to?

A

Bone

118
Q

Where does colorectal cancer commonly metastasise to?

A

Liver

119
Q

Where does ovary cancer commonly metastasise to?

A

Ometum/peritoneum

Year One - Principles of Disease (15 decks)

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