Tumour Pathology Flashcards
(190 cards)
1
Q
What is a tumour?
A
An abnormal growing mass of tissue
2
Q
Describe the growth of a tumour
A
Uncoordinated with that of surrounding normal tissues
Growth continues after the removal of any stimulus which may have caused the tumour
An irreversible change
3
Q
What is an alternative term for tumour?
A
A neoplasm
4
Q
What are the two types of tumours?
A
Benign - noncancerous
Malignant - cancerous
5
Q
What does metastasise mean?
A
The ability of cancer to spread - cancers invade adjacent tissue and grow at other sites within the body
6
Q
Define cancer
A
A malignant growth resulting in uncontrolled division of cells
7
Q
What are the general features of cancer?
A
The major cause of death in the UK
Incidence of specific types of cancer increasing (males>female)
Genetic and environmental factors are important in the causation
Multistep process
8
Q
What are the most common types of cancer in men?
A
- Prostate
- Lung
- Colon
- Kidney
- Melanoma (skin)
9
Q
What are the most common types of cancer in women?
A
- Breast
- Lung
- Colon
- Uterus
- Melanoma (skin)
10
Q
What are the most common types of cancer overall?
A
- Prostate
- Breast
- Lung
- Colon
- Melanoma
11
Q
What are the five-year survival rates of the most common cancers?
A
Melanoma - 90%
Breast - 85%
Prostate - 85%
Uterus - 80%
Kidney - 60%
Colon - 60%
Lung - 10%
12
Q
How are tumours classified?
A
- Based on the tissue of origin
- Benign vs malignant
13
Q
What are examples of tissues from which tumours can arise?
A
Epithelium
Connective
Blood cells
Lymphoid tissues
Melanocytes
Neural tissue
Germ cells (ovary/testis)
14
Q
What is the nomenclature of epithelial tissues?
A
Glandular
Benign: Adenoma
Malignant” Adeno-carcinoma
Squamous
Benign: Squamous papiloma
Malignant: Squamous carincoma
15
Q
What are the names given to benign tumours that arise from connective tissues?
A
Bone - Osteoma
Fat - Lipoma
Fibrous tissue - Fibroma
16
Q
What are the names given to malignant tumours for the connective tissues
A
Bone - Osteosarcoma
Fat - Liposarcoma
Fibrous tissue - Fibrosarcoma
17
Q
What is the (malignant) tumour of the white blood cells called?
A
Leukaemia
No known benign tumours
18
Q
Are there any tumours of the red blood cells?
A
No
19
Q
What is the name given to (malignant) tumours of the lymphoid tissue?
A
Lymphoma
No known benign tumours
20
Q
What names are given to tumours that arise from melanocytes?
A
Benign: Naevus
Malignant: Melanoma
21
Q
What are tumours of the central nervous system called?
A
Astrocytoma
22
Q
What are tumours of the peripheral nervous system called?
A
Schwannoma
23
Q
What are germ cell tumours collectively known as?
A
Teratomas
24
Q
Key points of the germ cell tumours
A
A tumour composed of different tissues
Develop in either the ovary or testis
Ovarian teratomas are usually benign
Testicular teratomas are usually malignant
25
What are features of benign tumours?
Non-invasive growth pattern
Usually encapsulated (contained)
No evidence of invasion
No metastases (does not spread)
Cells are similar to normal, healthy cells
Well-differentiated (look similar to nearby tissue)
Function similar to normal tissue
Rarely cause death
26
Features of Malignant Tumours
Invasive growth pattern
No capsule or the capsule is breached by tumour cells
Abnormal cells
Poorly differentiated
Loss of normal function
Frequently cause death
27
What are tumour suppressor genes?
A tumour suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication.
They inhibit cell proliferation and tumor development.
28
What is an oncogene?
A gene which in certain circumstances can transform a cell into a tumour cell.
29
What are the properties of cancer cells?
Loss of tumour suppressor genes
Gain of function of oncogenes
Altered cellular function
Abnormal morphology
Cells capable of independent growth
Presence of tumour biomarkers
30
What are examples of tumour suppressor genes?
Adenomatous polyposis (APC) - involved in colon cancer
Retinoblastoma (Rb) - involved in tumours of the retina of the eye
BRCA1 - involved in breast cancer
31
What are examples of oncogenes?
B-raf
Cyclin D1
ErbB2
c-Myc
K-ras
N-ras
32
What is B-raf associated with?
A range of tumours including melanoma
33
What is Cyclin D1 associated with?
Lymphoma
34
What is ErbB2 associated with?
Several types of tumours
35
What is c-Myc associated with?
Lymphoma
36
What are K-ras and N-ras associated with?
Several types of tumours but most notably colorectal cancer
37
What is a tumour biomarker?
Tumour-related proteins
38
What are the different categories of tumour biomarkers?
Onco-fetal proteins
Oncogenes
Growth factors and receptors
Immune checkpoint inhibitors
39
Describe the cellular function of cancer cells
Loss of cell-to-cell adhesion
Altered cell-to-matrix adhesion
Production of tumour related proteins aka biomarkers
40
What is the clinical usage of tumour biomarkers?
Screening
Diagnosis
Prognostic - identifying patients with a specific outcome
Predictive - identifying patients who will respond to a particular therapy
41
What is the biomarker for Teratoma of testis and hepatocellular carcinoma?
Alpha-fetoprotein
42
Where does hepatocellular carcinoma arise from?
Liver cancer arises from cells of the liver
43
What is the biomarker for colorectal cancer?
Carcino-embryonic antigen
44
What is the biomarker for Breast cancer?
Oestrogen receptor
45
What is the biomarker for Prostate cancer?
Prostate specific antigen
46
What are the predictive tumour biomarkers for colorectal cancer?
K-ras, an oncogene
47
What are the predictive tumour biomarkers for lung cancer?
EGFR - epidermal growth factor receptor
PD-L1 - an immune checkpoint
48
What are the predictive tumour biomarkers for breast cancer and gastric cancer?
Her2
49
What are the predictive tumour biomarkers for melanoma?
Braf
50
What is the variation in size and shape of cancer cells referred to as?
Pleomorphism
51
Is mitosis present in cancer cells?
Yes however it is abnormal
52
What is tumor growth?
A balance between cell growth and cell death
53
What two processes are vital in tumour growth?
Angiogenesis
Apoptosis
54
What is angiogenesis?
Angiogenesis is the formation of new blood vessels by tumors which is required to sustain tumor growth.
The more blood vessels in a tumour, the poorer the prognosis
55
What does angiogenesis provide a route to?
Release of tumour cells
56
What is apoptosis?
Mechanism of programmed and controlled single cell death.
It is an active cell process that regulates tumour growth and is involved in response to chemotherapy and radiotherapy.
57
How can the spread of cancer be divided up?
Invasion
Metastasis
58
What is a major clinical problem of cancer?
Formation of metastatic (secondary) tumours
Prognosis depends on extent of cancer spread
59
What are the characterizations of invasion and metastasis?
- Multi-step process
- Increased matrix degradation by proteolytic enzymes
- Altered cell-to-cell and cell-to-matrix adhesion
60
What are the modes of cancer spread?
Local - spread to adjacent anatomical structures. Invasion.
Lymphatic
Blood
Trans-coelomic - a special type of local spread. Spread between body cavities ie the pleural cavity
61
Steps in tumour invasion
Malignant tumout
Invasion into connective tissue
Invasion into lymph/blood vessles
62
Steps of tumor metastasis via lymphatics
Adherence of tumor cells to lymph vessels
Invasion from lymphatics
Invasion into the lymph node
Formation of metastasis in lymph node
Clinical evidence of metastasis
63
Steps of tumor metastasis via blood
Adherence of tumour cells to blood vessels
Invasion from blood vessels
Invasion into tissue
Formation of metastasis
Clinical evidence of metastasis
64
What type of tumors show trans-coelomic spread?
Tumours of lung, stomach, colon and ovary
65
What are the common sites of metastasis?
Liver, lung, brain, bone (axial skeleton), adrenal gland, omentum/peritoneum
66
What are the uncommon sites of metastasis?
Spleen, kidney, skeletal muscles, heart
Relates to blood flow and the environmental factors of each organ
67
Where do breast, prostate, and colorectal cancer often metastasize to?
Breast - bone
Prostate - bone
Colorectal - liver
Ovary - omentum/peritoneum
68
Local effects of benign tumors
Pressure
Obstruction - especially if the tumor is in a hollow structure such as the intestine
69
Local effects of malignant tumours
Pressure
obstruction
Tissue destruction - ulceration/infection
Bleeding, if tumour erodes into blood vessels- anemia, haemorrhage
Pain - pressure on nerves, perineural infiltration (area surrounding the nerves), bone pain from pathological fractures
Effects of treatment
70
What is perineural infiltration?
The process of neoplastic invasion of nerves and is an under-recognized route of metastatic spread.
71
What are systemic effects of a malignant tumour?
Unplanned weight loss may amount to cancer cachexia if weight loss is significant and sustained
Secretion of hormones - can be either normal or abnormal. Can also promote weightloss.
Paraneoplastic syndromes - a group of uncommon disorders that develop in some people who have cancer
Effects of treatment
72
What is normal hormone production by tumors?
Hormones are produced by tumors of the endocrine organ but there is abnormal control of hormone production/secretion
Secreted either at an inappropriate time or in response to an inappropriate stimulus or in an appropriate amount.
73
What is abnormal hormone production by tumors?
Produced by tumour from an organ that does not normally produce hormones
74
What is an abnormal hormone secretion caused by lung cancer tumours?
ACTH
ADH
75
What are paraneoplastic syndromes?
Cannot be explained by local or metastatic effects of tumors eg neuropathy, myopathy
76
Why is it important to detect cancer at an early stage?
Reduce/prevent morbidity and moratlity
77
Morbidity vs morality
Morbidity refers to an illness or disease.
Mortality refers to death.
78
How can cancer be detected at a pre-invasive stage?
Detection of dysplasia/intraepithelial neoplasia
79
What is dysplasia?
Dysplasia is a broad term that refers to the abnormal development of cells within tissues or organs.
80
Features of dysplasia
Pre-malignant change
Earliest change in the process of malignancy that can be visualized
Identified in the epitheliuim
No invasion but can progress to cancer
81
What are the features of dysplasia?
Disorganisation of cells - increased nuclear size, mitotic activity and abnormal mitoses
Grading of dysplasia - low and high
No invasion
82
What does early detection of cancer need?
Effective test that is sensitive/specific and accetable
83
What is cervical cancer screening used to reduce?
Detects oncogenic HPV of the squamous carcinoma of the cervix to rncidence of the squamous carcinoma of the cervix
Established NHS program
84
What is the cell cycle defined as?
The interval between mitotic divisions
85
What are the external factors that affect cell cycle control?
Hormones, growth factors, cytokines, stroma
86
When is the cell cycle dependant on external stimuli and when is it autonomous?
Prior to restriction point - external stimuli
After restriction point - autonomous
87
What is the genome chromosome pair?
The human genome is stored on 23 chromosome pairs. 22 of these are autosomal chromosome pairs, while the remaining pair is sex-determining.
88
How many chromosomes are in a cell?
23 pairs of chromosomes
46 total chromosomes
89
What does each turn of the cell cycle do?
Divides the chromosomes in a cell nucleus
90
What does mitosis start and end as?
Diploid cell produced 2 genetically identical diploid cells
91
What does meiosis start and end as?
Diploid cell produces 4 haploid daughter cells
92
What are the three periods the cell cycle can be divided into?
Interphase
Mitosis
Cytokinesis
93
What happens in interphase?
Cell grows and accumulates nutrients needed for mitosis;
Cell is synthesizing RNA, producing protein and growing in size.
The molecular events that regulate the cycle are ordered .
94
What stages make up interphase?
G1
S
G2
95
What happens during mitosis?
Cell splits itself into two genetically identical daughter cells (diploid cells)
96
What happens during cytokinesis?
New cell is completely divided
97
What happens in G1?
Cell increases in size
Cellular contents are duplicated
98
What happens in S phase?
DNA replication
Each of the 46 chromosomes (23 pairs) is replicated by the cell
99
What happens in G2?
Cell grows more
Organelles and proteins develop in preparation for cell division
100
What happens in M phase?
Mitosis followed by cytokinesis (cell separation)
Formation of two identical daughter cells
101
What happens in G0?
While some cells are constantly dividing, some cell types are quiescent.
These cells exit G1 and enter a resting state called G0.
In G0, a cell is performing its function without actively preparing to divide. G0 is a permanent state for some cells, while others may re-start division if they get the right signals.
102
What is the progression of cells through the cell cycle is controlled by?
By various checkpoints at different stages.
103
What do checkpoints in the cell cycle detect and what does it do?
If a cell contains damaged DNA and ensure those cells do not replicate and divide.
104
Where can the restriction checkpoint (R) be found?
The restriction point (R) is located at G1 and is a key checkpoint.
The vast majority of cells that pass through the R point will end up completing the entire cell cycle.
105
What happens if damaged DNA is detected during any checkpoint?
Activation of the checkpoint results in increased p53 protein production.
106
What is p53 and what does it do?
A tumour suppressor gene
Stops progression of the cell cycle and starts repair mechanisms for the damaged DNA.
107
What happens to damaged DNA if they can not be repaired by p53?
The cell undergoes apoptosis and can no longer replicate.
108
What are the checkpoints in the DNA cycle?
G1
G2
Metaphase
109
What does the G1 checkpoint detect?
Inadequate nutrient supply
External stimulus lacking
Abnormal cell size
DNA damaged
110
What does the G1 checkpoint detect?
Abnormal cell size
DNA damage
Unreplicated DNA
111
If the DNA is not replicated, where will the cell cycle cease?
S phase
112
If DNA damage is detected, where will the cell cycle cease?
G1 or G2
113
If there is chromosome misalignment, where will the cell cycle cease?
Metaphase
114
What is the main purpose of the G1, G2 and M phase checkpoints?
G1 - Checks DNA integrity
G2 - Checks proper
chromosome duplication
M - Assesses attachment of each kinetochore to a spindle fiber
115
What is an example of a tumour suppressor protein that works in the cell cycle?
Retinoblastoma protein (Rb).
Rb restricts the ability of a cell to progress from G1 to S phase in the cell cycle.
116
What does CDK do?
CDK phosphorylates Rb to pRb, making it unable to restrict cell proliferation, thereby inhibiting its cell growth-suppressing properties.
This allows cells to divide normally in the cell cycle.
117
What external facts can affect the cell cycle?
Cytokines
Growth factors
Horomes
118
What is the role of cytokines?
Cytokines regulate cell proliferation by cell-cycle-regulatory proteins, in which cyclin-dependent kinase inhibitors (CDKI) inhibit cell proliferation.
119
What are the catalytic sub-units called and what are they activated by?
Cyclin dependant kinases Activated by a regulatory sub-units called cyclins
120
What is the name given to the active enzyme complex?
CDK/cyclin complex
121
What is the effect of CDK/cyclin complexes?
Phosphorylate target proteins
122
What is the result of the CDK/cyclin complexes phosphorylating the target proteins?
Results in activation or inactivation of that substrate
123
What is the function of the substrates that are inactivated or activated by CDK/cyclin complexes?
Substrates regulate what happens in the next phase of the cell cycle
124
How are CDK's and cyclins regulated?
CDK's are constitutively expressed in an inactive form
Cyclins accumulate and are destroyed as cycle progresses
CDK inhibitors
124
How are CDK's and cyclins regulated?
CDK's are constitutively expressed in an inactive form
Cyclins accumulate and are destroyed as cycle progresses
CDK inhibitors
125
What are the two methods of inhibition of the CDK inhibitors?
Bind to CDK and prevent the association of these CDK's with their cyclin regulatory proteins. They bind to the CDK/cyclin complexes
126
What are the environmental factors that can cause genetic damage?
Chemicals
Radiation
Oncogenic viruses
127
What are the targets for radiation carcinogenesis?
Purine and pyrimidine bases
128
Which forms of high energy radiation are carcinogenic?
Ultraviolet radiation
X rays
Gamma radiation
129
Which genes mutate at G1-S to cause cancer?
Rb, CDK4, Cyclin D and p16
130
What is the function of P53?
Maintains genomic integrity
131
What is the effect of increased levels of P53?
Cell cycle arrest at G1
Facilitates DNA repair
Apoptosis
132
What is the effect of a mutated P53 gene?
No G1 arrest or repair of DNA
Genetically damaged cells proliferate and form malignant neoplasms
133
What are the cell cycle inhibitors?
CDK inhibitors (CDKIs) - inhibitor molecules binding to cyclin/CDK complexes
134
What are the two families of genes that prevent cell cycle progression ?
INK41 gene family - p16
GIP/KIP gene family - p21, p27
135
What is the function of the pRb phosphoprotein?
CDK/cyclin complexes phosphorylate this protein. Once phosphorylated it becomes inactive and loses affinity for the E2F transcription factor.This free E2f now activates vital target genesE2F is a potent stimulator of cell cycle entry
136
What does cell cycle balance?
Propliferation and apoptosis
137
What is carcinogenesis?
Failure of cell cycle control, balance between proliferation and apoptosis is distrupted
138
What causes carcinogenesis?
Mutations in genes regulating cell division, apoptosis, and DNA repair cause a cell to lose control of proliferation
139
What does uncontrolled proliferation of cells cause?
Tumours
140
What are the two regulatory pathways disrupted in carcinogenesis?
1.The cyclin D-pRb-E2F pathway
2. p53 pathway
141
Where are all cancers dysregulated?
G1-S
142
What are mutated cell cycle regulating genes?
Cyclin D
CDK4
p16
Rb
143
How do tumour suppressor genes function?
Discourage cell growth or temporarily halt cell division to carry out DNA repair
144
What is an anti-oncogene?
A tumour suppressor gene
Responsible for Apoptosis
DNA repair and the negative regulation of mitosis
145
What do mutations in retinoblastoma gene cause?
Favour cell proliferation since it is an anti-oncogene (a tumour suppressor gene)
146
What other mutations can cause the same effect of a mutated RB gene?
Mutational activation of Cyclin or CDK (naturally responsible for the phosphorylation of the pRB)
Mutational inactivation of CDKI's
147
What is the inherited form of oncogenesis?
One defective copy of the RB gene
Somatic point mutation of the other copy
148
What is the sporadic form of oncogenesis?
Both hits occur in a single cell
149
What does mutation of tumour suppressor genes cause?
Loss of function
150
What is the two hit hypothesis of tumour suppressor genese?
Tumour suppressor alleles are usually recessive
Loss of both normal allelic copies gives rise to cancer
151
Discuss inherited cancer
Account for 5-10% of all cancers
Genetic predisposition to develop cancer
Early onset of multiple tumours
152
Discuss the inherited predisposition to familial retinoblastoma cancer
Carriers have 10000x risk of bilateral retinoblastoma
Increased risk of second cancers eg bone sarcomas
Autosomal dominant pattern
153
Discuss the inherited predisposition to familial adenomatous polyposis of colon
Thousands of polyps
100% risk of colon cancer by age 50 years
Caused by a defect in the adenomatous polyposis coli (APC) gene.
Autosomal dominant pattern
154
Discuss the inherited predisposition to Hereditary Non-polyposis Colorectal Cancer Syndrome
Germline mutations in DNA mismatch repair genes
hMSH2, hMLH1, MSH6
Autosomal dominant inheritance.
155
What is the function and the inherited mutation of APC?
Function: Signal transduction
Inherited mutation: FAP colon cancer
156
What is the function and the inherited mutation of p53?
Function: cell cycle/apoptosis after DNA damage
Inherited mutation:
Li-Fraumeni syndrome:
Multiple carcinomas and sarcomas
157
What is the function and the inherited mutation of Rb?
Function: Cell cycle regulation
Inherited mutation: Retinoblastoma, osteosarcoma
158
What is the function and the inherited mutation of p16(INK4a)?
Function: inhibits CDK's
Inherited mutation: malignant melanoma
159
What are proto-oncogenes?
Normal genes coding for normal growth regulating proteins:
Growth factors
Growth factor receptors
Signal transduction
160
What are cancer causing genes?
Oncogenes that are derived from proto-oncogenes
161
Which gene is responsible for DNA repair and causes breast and ovarian cancer?
BRAC 1/2
162
What are oncogenes activated by?
Alteration of proto-oncogene structure
163
What happens when there is dysregulation of proto-oncogene expression?
Gene amplification
Over expression
164
What can cause dysregulation of proto-oncogene expression?
Gene amplification
Over expression
165
What can cause alteration of proto-oncogene structure?
Point mutation
Chromosome rearrangements + translocations
166
Give examples of oncoprotein products
Growth factors
Growth factor receptors
Proteins involved in signal transduction
Nuclear regulatory proteins
Cell cycle regulators
167
What mutation of the PDGF growth factor causes Astrocytoma and osteosarcoma's?
Over expression
Proto-oncogene: sis
168
What mutation of the growth factor receptor EGF causes Breast ovarian lung and stomach cancer?
Amplification
Proto-oncogene: HER2/neu
169
What mutation in GTP binding signal transducaers causes lung, colon, pancreas, leukaemia?
Point mutation
Proto-oncogene: ras
170
What mutation in transcriptional activators (a nuclear regulatory protein) causes Burkitt lymphoma?
Translocation
Proto-oncogene: myc
171
What type of mutation are cell cycle regulators Cyclin D and CDK4 susceptible to?
Amplification
Cyclin D also susceptible to translocation
172
What type of cancer can a mutation in Cyclin D cause?
Translocation - mantle cell lymphoma
Amplification - breast, liver, oesophageal
173
What type of cancer does a mutation in cyclin dependant kinase cause?
Melanoma, sarcoma
174
What are the mechanisms of viral carcinogenesis?
Virus genome inserts near a host proto - oncogene
Viral promoter or other transcription regulator causes proto-oncogene over expression
Retroviruses insert oncogene into host DNA causing cell division.
175
Chemical carcinogenesis involves adduct formation, what does this lead to?
Activation of oncogenes and suppression of anti-oncogenes
176
What is a neoplasm?
A new and abnormal growth of tissue in the body.
177
What is the function of the p16 protein?
It is an inhibitor of the CDK's which are involved in the phosphorylation of the of the pRB - progression from G1 to S phase
178
What happens when pRB is bound to E2F?
The complex acts as a growth suppressor - prevents progression through the cell cycle
When unbound - no inhibition exists - progression is possible
179
Discuss multistep carcinogenesis?
All sporadic cancers harbour multiple genetic aberrations
Mutations accumulate with time
Activation of several oncogenes and loss of two or more anti-oncogenes occurs in most cancers
180
What causes chemical carcionogenesis?
Purine and pyrimidine bases in DNA are critically damaged by oxidizing and alkylating agents
Chemical carcinogens react with DNA forming covalently bound products (DNA adducts)
Adduct formation can lead to activation of oncogenes and loss of anti-oncogenes
181
What causes viruses can cause cancer?
HPB - genital, throat and anal cancers
Hep B - liver cncer
EBV - lymphoma
182
What are the stages of mitosis?
Prophase
Metaphase
Anaphase
Telophase
183
What can help you remember stages of mitosis?
Pee on the MAT
184
What happens in interphase?
The cell spends most of its life in this phase. The DNA in chromosomes copies itself ready for mitosis.
185
What happens in prophase?
The DNA in chromosomes and their copies condenses to become more visible. The membrane around the nucleus disappears.
186
What happens in metaphase?
The nuclear membrane breaks down. Chromosomes and their copies line up in the middle of the cell.
187
What happens in anaphase?
Chromosomes and their copies are pulled to different ends of the cell.
188
What happens in telophase?
New membranes form around the chromosomes at each end of the cell.
189
What happens in cytokineses?
The cell membrane pinches in and eventually divides into two daughter cells.
