Neoplasia (PPT) Flashcards
1
Q
An abnormal mass of tissue the growth of which exceeds and is uncoordinated with that of normal tissue and persists in the same excessive manner after cessation of stimuli which evoked the change
A
Neoplasia
2
Q
This means new growth
A
Neoplasm
3
Q
Onco means
A
Tumoe
4
Q
Term used to describe malignant epithelial tumor
A
Carcinoma
5
Q
Term used to describe malignant mesenchymal tumor
A
Sarcoma
6
Q
Nomenclature of tumors are based on its
A
Biologic behavior
Tissue of origin
7
Q
Types of biologic behavior
A
Benign
Malignant
8
Q
Different tissue of origin
A
Epithelial
Mesenchymal
Mixed
Teratoma
9
Q
Characteristics of squamous cell carcinomas
A
Lots of desmosomes and tonofilaments on EM
Lone apoptosis
Keratin pearls
Tumor cells are strikingly similar to normal squamous epithelial cells
10
Q
Two types of mixed tumors
A
With mixed differentiation
Teratoma
Aberrant differentiation (not true neoplasms)
11
Q
Example of tumors with mixed differentiation
A
Pleomorphic adenoma
Wilm’s tumor
12
Q
Carcinosarcoma
A
Tumors with mixed differentiation
13
Q
Tumor comprised of cells from more than one germ layer
A
Teratoma
14
Q
Arise from totipotent cells (usually gonads)
A
Teratoma
15
Q
Benign cystic teratoma of ovary
A
Most common teratoma
16
Q
Aberrant differentiation that is characterized by disorganized mass of tissue whose cell types are indiginous to the site of the lesion
A
Hamartoma
17
Q
Aberrant differentiation characterized by ectopic focus of normal tissue (heterotopia)
A
Choriostoma
18
Q
Misnomers in neoplasia
A
Hepatoma: malignant liver tumor
Melanoma: malignant skin tumor
Seminoma: malignant testicular tumor
Lymphoma: malignant tumor of lymphocytes
19
Q
Benign tumor composed of smooth muscle cells
A
Leiomyoma
20
Q
Characteristics of Leiomyoma
A
Display typical characteristics of benignity, well-delineation, non-necrotic and non-invasive
21
Q
Analogy. Fat cells
Lipoma: __________
Liposarcoma: ___________
A
Lipoma: Mature fat cells
Liposarcoma: Immature fat cells (lipoblasts)
22
Q
Bulky tumor affecting the femur
A
Osteosacroma
23
Q
Defining feature of osteogenic sarcoma
A
Malignant osteoid
Matrix secreted by osteoblast
24
Q
Features of rhabdomyosarcoma
A
Anaplastic tumor
Marked cellular and nuclear pleomorphism
Hyperchromatic nuclei
Tumor giant cells
25
True or False.
As the cell population expands, a progressively higher percentage of tumor cells leaves the replicative pool by reversion to G0, differentiation, and death.
True
26
Danger signals of cancer
| Mnemonic: CAUTION US
```
Change in bowel or bladder habits
A sore that does not heal
Unusual bleeding or discharge
Thickening or lump (breast or elsewhere)
Indigestion or difficulty of swallowing
Obvious change in a mole or a wart
Nagging cough or hoarseness
Unexplained anemia
Sudden unexplained weight loss
```
27
True or False.
Presence of the danger signs/symptoms do not necessarily mean one has cancer. But having these symptoms should compel one to see a physician.
True
28
Estimated highest cancer incidence in males and females
Males: Prostate
Female: Breast
29
Estimated highest cancer death in males and females
Male: Lungs
Females: Lungs
30
True or False.
| The occurrence of cancers is related to components of the environment.
True.
31
In both sporadic and familial form of retinoblastoma, mutations happen on the
Retinal cells
32
Defective gene in retinoblastoma
RB gene
33
Transfer of defective RB gene in familial form retinoblastoma is based on what type of heredity
Autosomal dominant
34
Triggered pathways of apoptosis and mechanisms used by tumor cells to evade cell death
CD95 receptor–induced and DNA damage
35
Role of APC
Regulate the stability and function of B-catenin
36
Biologic behavior of tumors depend on
Rate of Growth
Degree of Differentiation
Local Invasion
Presence or absence of Metastasis
37
Hallmark of malignancy
Metastasis
38
Benign or Malignant.
| Well-circumscribed
Benign
39
Benign or Malignant.
| Ill-defined.
Malignant
40
Benign or Malignant.
| Encapsulated
Benign
41
Benign or Malignant.
| Irregular margins
Malignant
42
Benign or Malignant.
| Well-differentiated
Benign
43
Benign or Malignant.
| Anaplastic
Malignant
44
Benign or Malignant.
| Pushing margins
Benign
45
Benign or Malignant.
| Presence of invasion/metastasis
Malignant
46
Benign or Malignant.
| Absence of metastasis
Benign
47
Rate of growth in neoplasia is determined by
Doubling time of the tumor cells
Fraction of tumor cells that are in the replicative pool
Rate at which cells are shed and lost in the growing lesion
48
Fraction of tumor cells that are in the replicative pool
Growth fraction
49
Provides surveillance mechanisms for ensuring that critical transitions occur in the correct order with fidelity in their completion
Cell growth checkpoint
50
Cause cell cycle arrests by promoting inhibitory pathways or inhibiting activation pathways
Cell growth checkpoint
51
p53 activation in response to DNA damage which in turnm activate p21 (CDK inhibitor
Cell growth checkpoint
52
Mechanism of apoptosis
Abnormal mitochondrial membrane permeability ➡️ allows escape of cytochrome-c into the cystosol ➡️ activates proteolytic enzymes (caspases) ➡️ execution of the process ➡️ removal of dead cell fragments by phagocytosis without inflammatory reactions
53
Crucial event that initiates apoptosis
Abnormal mitochondrial membrane permeability
54
True or False.
| Apoptosis goes through several complex phases
True
55
Apoptotic pathway that is the result of increased mitochondrial permeability and release of pro-apoptotic molecules intocytoplasm (no death receptors)
Intrinsic (mitochondrial) pathway
56
Types of injury that initiate the intrinsic pathway
Radiation, toxins, free radicals, hypoxia, withdrawal of growth factors or hormones
57
Injury to the mitochondria stimulates the production of these anti-apoptotic components
Bcl-2
| Bcl-x
58
Intrinsic pathway can be inhibited to protect virally infected cells from Fas apoptosis by
FLIP
59
True or False.
In intrinsic pathway, death agonists cause changes in the inner mitochondrial membrane, resulting in the mitochondrial permeability transition (MPT) and release of cytochrome c and other pro apoptotic proteins into the
cytosol, which activate caspases. AIF, Apoptosis-inducing factor.
True
60
Mechanism of extrinsic (death-receptor-initiated pathway of apoptosis)
1. Fas cross linked to FasL.
2. 3 death domains (FAD) come together and form binding site for and adaptor protein.
3. FADD attached to death receptors binds inactive caspase-8 which come together and autocatalytically activated to active caspase-8
4. Cascade of other caspase activates executioner caspases.
5. Apoptosis initiated
61
Lack of differentiation
Anaplasi
62
The extent to which parenchymal cells resemble comparable normal cells, both morphologically and functionally
Differentiation
63
Disordered growth
| Disordered maturation
Dysplasi
64
Characteristics of Anaplasia
```
Pleomorphism
Hyperchromaticity
Increased nucleocytoplasmic ratio
Abnormal (atypical) mitotic figures
Loss of polarity (loss of orientation)
Presence of multiple or enlarged nucleoli
Formation of tumor giant cells
```
65
Malignant cells confined to epithelial lining (intraepithelial and intramucosal), limited by the basement membrane
In-situ
66
Malignant cells have breached basement membrane and are in the sub-epithelial stroma, lamina propria or submucosa
Invasive
67
Examples of intraepithelial neoplasia
Cervical, valvular, vaginal
68
Local invasion include
Invasion through basement membrane,
Invasion into lamina propria
Invasion through muscularis mucosa
69
Metastasis include
Contiguous invasion to adjacent organ
Seeding of body cavities/fluids
Lymphatic spread
Hematogenous spread
70
Sequence of events in invasion of intracellular matrix
1. Detachment of tumor cells (E-cadhedrins)
2. Attachment to matrix components (Laminin, Fibronectins)
3. Degradation of extracellular matrix (Collagenase, cathepsin D)
71
Vascular dissemination/homing
Vascular/lymphatic drainage in microenvironment
72
Eight fundamental physiological changes in the neoplastic cell
Mnemonic: SA3LISE
```
Self-sufficiency in growth signals
Ability to invade and metastasize
Ability to evade host response
Altered cellular metabolism
Limitless replicative potential Insensitivity to growth-inhibitory signals
Sustained angiogenesis
Evasion of APOPTOSIS
```
73
Mechanism of cell proliferation
1. Binding of growth factor to receptor on the cell membrane
2. Stimulation of GF to activate several signal transducing proteins on the membrane
3. Transmission of signals via 2nd messengers or cascade of signal transduction molecules
4. Induction and activation of nuclear regulatory factors that initiate DNA transcription
5. Entry and progression of the cell into the cell cycle resulting in cell division
74
True or False.
| Disorder of cell growth and behavior, must be defined at the cellular and molecular level.
True
75
Predominant cause of sporadic cancers
Somatic mutations (frequently due to environmental factor)
76
Other causes of sporadic cancers
Age
Heredity
Acquired preneoplastic disorders
77
In very young and very old individuals
Somatic mutations increase
| Immune competence decrease
78
Familial cancer are commonly seen in
Early age, tumors among close relatives or multiple or bilateral tumors
79
True or False.
| Nonlethal genetic damage lies at the heart of carcinogenesis.
True.
80
```
True or False.
Nongenetic damage (or mutation) may be acquired by the action of environmental agents, such as chemicals, radiation, or viruses, or it may be inherited in the germ line.
```
True.
81
True or False.
The genetic hypothesis of cancer implies that a tumor mass results from the clonal expansion of a single progenitor cell that has incurred genetic damage (i.e., tumors are monoclonal).
True
82
Four classes of normal regulatory genes
1. growth-promoting proto-oncogenes,
2. growth-inhibiting tumor suppressor genes,
3. genes that regulate programmed cell death (i.e., apoptosis)
4. genes involved in DNA repair-are the principal targets of genetic damage
83
Tumor suppressor genes that release breaks on cell proliferation, also called promoters
Rb
| p53
84
Tumor suppressor genes that ensures integrity of the genome, also called caretakers
DNA repair genes
85
Genes that regulate apoptosis
Proto-oncogenes
86
Dominant genes that may also behave as tumor suppressor genes
Proto-oncogenes
87
Two general groups to tumor suppressor genes
Promoter genes
| Caretaker genes
88
The traditional tumor suppressor genes, such as RB or p53, where mutation of the gene leads to transformation by releasing the brakes on cellular proliferation.
Promoters
89
Responsible for processes that ensure the integrity of the genome, such as DNA repair.
Caretaker genes
90
True or False.
| Mutation of caretaker genes does not directly transform cells by affecting proliferation or apoptosis.
True
91
True or False.
DNA repair genes affect cell proliferation or survival indirectly by influencing the ability of the organism to repair nonlethal damage in other genes, including proto-oncogenes, tumor suppressor genes, and genes that regulate apoptosis.
True
92
True or False.
A disability in the DNA repair genes can predispose cells to widespread mutations in the genome and thus to neoplastic transformation.
True
93
Encode proteins that normally inhibit cell proliferation
Tumor suppressor genes
94
Cel surface protein of tumor suppressor genes
DCC (cell adhesion)
95
Signal transduction protein of tumor suppressor genes
NF-1 (GTPase activator)
96
True or False.
Most oncogenic RAS are mutations with a single base pair change that alters an amino acid at position 12, 13, or 61 in the protein product.
True.
97
Proteins that regulate transcription
p53, pRb
98
True or False.
RAS mutations destroy GTP-ase activity but retains GTP-binding activity, and current thinking is that these stay locked "on", telling the transformed cell, "Keep dividing!"
True
99
Genes that promote autonomous cell growth in cancer cells
Oncogenes
100
They are derived by mutations in proto-oncogenes and are characterized by the ability to promote cell growth in the absence of oncoproteins
Oncogenes
101
Normal growth-promoting signals products that resemble the normal products of proto-oncogenes except these are devoid of important regulatory elements, and their production in the transformed cells does not depend on growth factors or other external signals
Oncoproteins
102
Most commonly activated by point mutations.
RAS
103
Mutations in these locations interfere with GTP hydrolysis that is essential to convert RAS into an inactive form
Three hotspots which encode residues either within the GTP-binding pocket or the enzymatic region essential for GTP hydrolysis
104
When mutations in the three hotspots occur
RAS is trapped in its activated GTP-bound form
| The cell is forced into a continuously proliferating state
105
True or False.
All signal transduction pathways enter the nucleus and have an impact on a large bank of responder genes that orchestrate the cells' orderly advance through the mitotic cycle
106
Ultimate consequence of signaling through oncogenes like RAS or ABL is
inappropriate and continuous stimulation of nuclear transcription factors that drive growth-promoting genes
107
Consequence of mutations affecting genes that regulate transcription of DNA
Growth autonomy
108
Gene that can either activate or repress the transcription of other genes
MYC gene/protein
109
Activate MYC
Growth-promoting genes, including cyclin-dependent kinases (CDKs)
110
Repress MYC
CDK inhibitors
111
Mechanism by which MYC promotes turmorigenesis
Increasing expression of genes that promote progression through the cell cycle and repressing genes that slow or prevent progression through the cell cycle
112
Dysregulation of the MYC gene resulting from a t(8;14) translocation occurs in
Burkitt lymphoma, a B-cell tumor
| amplified in breast, colon, lung, and many other cancers
113
Amplified in neuroblastomas and small-cell cancers of lung
The related N-MYC and L-MYC genes
114
Governor of proliferation
Rb gene
115
First tumor suppressor gene discovered
Rb gene
116
Product of Rb gene
DNA-binding protein that is expressed in every cell type examined, where it exists in an active hypophosphorylated and an inactive hyperphosphorylated state
117
The importance of the Rb lies in
its enforcement of G1, or the gap between mitosis (M) and DNA replication
118
Initiation of DNA replication requires the activity of
Cyclin E/CDK2 complexes
119
Expression of cyclin E is dependent on the
E2F family of transcription factors
120
True or False.
Early in G1, Rb is in its hypophosphorylated active form, and it binds to and inhibits the E2F family of transcription factors, preventing transcription of cyclin E.
True
121
Hypophosphorylated RB blocks
E2F-mediated transcription
122
One of the most commonly mutated genes in human cancers
p53
123
Mutations in p53 causes
Activation of temporary cell cycle arrest
Induction of permanent cell cycle arrest
Triggering of programmed cell death
124
Temporary cell cycle arrest
Quiescence
125
Permanent cell cycle arrest
Senescence
126
Programmed cell death
Apoptosis
127
In other words, mutation on the p53 gene causes
Quiescence
Senescence
Apoptosis
128
Gene that senses DNA damage and assists in DNA repair by causing G1 arrest and inducing DNA repair genes
P53
129
A cell with damaged DNA that cannot be repaired is directed by p53 to either enter ___________ or undergo ____________.
senescence
| apoptosis
130
Guardian of the genome
p53
131
Mechanisms of cellular aging
DNA Damage
Decreased cellular replication
Reduced regenerative capacity of tissue stem cells
Accumulation of metabolic damage
132
DNA damage occurs through
Faulty DNA repair genes
| Calorie restriction
133
Incomplete replication and progressive shortening of telomeres that causes decreased cellular replication
Replicative senescence
134
Distinctive form of cellular metabolism with high level of glucose uptake and increased conversion to lactose fermentation via glycolytic pathway
Warburg effect
135
Aerobic glycolysis
Warburg effect
136
Provides rapidly dividing cells with metabolic intermediates needed for synthesis of cellular components
Warburg effect
137
Gene damage that further leads to clonal proliferation
Carcinogenesis
138
Mechanisms of carcinogenesis
Point mutation
Chromosomal translocation
Chromosome deletion
Gene amplification
139
DNA-binding protein proto-oncogenes
MYC family
140
Present in all eukaryotes, whose protein products are intranuclear and bind to DNA itself, enabling DNA synthesis
MYC
141
Activation is usually by amplification (excess copies of a gene) and/or translocation rather than by mutation
MYC
142
MYC causes
Gene amplification
143
Targets of genetic damage
Growth-promoting proto-oncogenes
Growth inhibiting cancer suppressor genes
Apoptosis-regulating genes
144
True or False.
The related neu (once erb2, now HER2) is amplified in many carcinomas, notably adenocarcinomas, especially of the breast, and the degree of amplification strongly correlates with bad outcome.
True
145
True or False.
| Carcinogenesis is a multistep process that causes tumor progression.
True
146
Neoplastic cell arise from a SINGLE CELL
| 30 population doubling time produce 109 cells = 1 gram
Clonality
147
Acquisition of permanent, irreversible qualitative changes in one or more characteristics of a neoplasm
Progression
148
Cellular genes that can become activated to become cancer causing oncogenes
Encode proteins involved in normal differentiation or proliferation
Proto-oncogenes
149
Inhibitor of apoptosis
Bcl-2
150
True or False.
Tumor-suppressor genes keep cells benign, even when the oncogenes are activated. To lose their anti-cancer effect, BOTH copies must be altered.
True
151
Biology of tumor growth
Tumor angiogenesis, progression and heterogeneity
152
Components of tumor angiogenesis
Vascular endothelial growth factor
Basic fibroblast growth factor
Anti-angiogenic factors
153
Factors causing tumor progression and heterogeneity
Increased aggressiveness
Genetic instability/random mutations
Loss of p53, DNA repair genes
154
Recognition and destruction of NON-SELF tumor cells upon their appearance
Immune surveillance
155
Components of immune surveillance
CD8+cytotoxic T cells (CTLs)
Natural killer cells
Macrophages
Humoral mechanism
156
Major defense mechanism againts tumors
CTLs
157
Categories of antigens
Tumor specific antigens
| Tumor-associated antigens
158
Tumor cells escape immunosurveillance by
Selective outgrowth of antigen negative variants
Loss or reduced expression of HLA antigens
Tumor-induced immunosuppression
No co-stimulation/no sensitization
Apoptosis of cytotoxic T-cells
159
Mechanisms of immune surveillance escape by tumor cells
Mutation
Downregulate MHC molecules on tumor cell surface
Lack of CO-stimulation molecules, e.g., (CD28, ICOS)
Immunosuppressive agents
Antigen masking
Apoptosis of cytotoxic T-Cells (CD8); damn tumor cell KILLS the T-cell
160
Mechanism of the activation of proto-oncogenes
Point mutation
Chromosome rearrangments
Gene amplification
161
DNA sequences within eukaryotic cells that seem to be involved in the development and maintenance of tumors
Oncogenes
162
Genes that direct the synthesis of proteins that under some conditions transform a benign host cell into a cancer cell
Oncogenes
163
Proto-oncogene minus its regulatory sequences, or with a characteristic mutation, or in an excessive number of copies ("amplification")
Viral oncogene
164
Capable of causing cancer by themselves, and hence are very different from their normal counterparts (i.e., have been damaged several times)
Viral oncogene
165
Examples of viral oncogene
Human Papilloma virus
Epstein-Barr Virus
Hepatitis B virus
166
HPV type that causes squamous cell carcinoma in the cervix
HPV 16 and 18
167
HPC type that causes genital warts
HPV 6 and 11
168
Diseases caused by EBV
Burkitt’s lymphoma: t(8,14)
Nasopharyngeal carcinoma
Lymphoma in AIDS
169
Hepatitis B virus causes
Hepatocellular carcinoma
170
Grading of neoplasia depends on
Differentiation of tumor (well, moderate, pootly differentiated)
171
Staging of neoplasia depends on
Timor size
Node involvement
Presence or absence of metastasis
172
Better method for prognosticating neoplasias
TNM system
173
Soft tissue tumors which are definitionally high grade
```
Ewing’s sarcoma
Rhabdomyosarcoma
Angiosarcoma
Pleomorphic liposarcoma
Soft tissue osteosarcoma
Mesechymal chondrosarcoma
Demspolastic small cell tumor
```
174
Grading of low grade soft tissue tumors
```
Well-differentiated liposarcoma
Atypical lipomatous tumor
Dermatofibrosarcoma protuberans
Infantile fribrosarcoma
Angiomatoid MFH
```
175
Atypically proliferating
Boderline tumors/low malignant potential
176
Criteria for Borderline Serous Tumors or APST
1. Stratification and budding in > 10% of tumor
2. Cribriform and micropapillary pattern less than 5mm area (if >5mm =>MPSC, micropapillary serous carcinoma)
3. Mitoses < 4 per 10 high power fields
4. Absence of stromal invasion
177
Laboratory Diagnosis of Cancer
Morphologic methods
Biochemical assays
Molecular diagnosis
Molecular profiling
178
Morphologic methods used to diagnose cancer
Cytology
Immunohistochemistry
Flow cytometry
179
Biochemical assay used to diagnose cancer
Tumor markers
180
Molecular diagnostics used to diagnose cancer
PCR/FISH
181
Molecular profiling used to diagnose cancer
DNA-microarray
182
Examples of cytologic procedures
Cervial pap’s smear
Fine needle aspiration biopsy
Frozen section diagnosis
183
In immunohistochemistry, the basic batteries used to differentiate tumors include
Cytokeratine
Vimentin
LCA
S-100/NSE
