Lecture | Neoplasms (part 2) Flashcards
Cancer grading is subjective and semi-quantitative. T/F
True
Is based on the degree of anaplasia and number of proliferating cells
Cancer grading
Is based on the shape and regularity of cells, presence and distinct differentiated features
Degree of anaplasia
Is based on evidence of rapid growth, which includes large number of mitoses, presence of atypical mitoses, nuclear pleomorphism, and tumor giant cells.
Number of proliferating cells
Tumor marker that can also be used yo quantify how much of these cells are actively proloferating
Ki67
Correlation of cytological grade and biological behavior is variable. T/F
True
The higher the anaplasia, the poorly differentiated the tumor, and the large number of mitosis correlates with a higher grade. T/F
True
Refers to the extent of tumor spread; influence choice of surgical approach or treatment modalities
Cancer staging
Criteria used in cancer staging:
- Tumor size,
- Extent of local growth,
- Presence of lymph node metastasis,
- Presence of distant metastasis
The bigger the tumor, the most likely it will be resectable. T/F
False,
… will not be resectable
One global scheme to address cancer staging; has a specific staging for particular malignancies in the different organs of the body
TNM cancer staging
What is TNM cancer staging?
T stands for Tumor - evaluates tumor size and the extent of its growth in relation to the structures that is located.
N stands for Nodal metastasis - pertains to the regional lymph nodes
M stands for Metastasis - refers to the distant metastasis
Most cancers arise from a single transformed cell. T/F
True. (Evidence-based)
Malignant change in the target cell is referred to as
Transformation
Stage 3 usually involves
Nodal metastasis
Stage 4 usually means that there is already
Distant metastasis
Transformation is the last step in the natural history of a malignant tumor. T/F
False,
It is the initial step
Accompanied by mutations of the DNA/genome of the cell
Transformation
Diagnosis should be early when the tumor is still small, when it is still amenable for resection. T/F
True
Additional treatment modalities if a tumor is very hard to manage due to late diagnosis.
Chemotherapy and radiation
Literally means abnormal growth
Dysplasia
Malignant transformation is a single-step process. T/F
False,
It is a multistep process
Precursor lesion of cancer
Dysplasia
In dysplasia, some features of malignancy are present microscopically. T/F
T
Dysplasia may develop into malignancy such as:
Uterine cervix and colon polyps
Dysplasia is irreversible like neoplasia. T/F
False,
It is still reversible unlike neoplasia
What is needed to remove in dysplasia so that the cells will go back to a normal state?
Instigating stimuli
If stimuli is not removed, dysplasia would eventually develop into malignancy
Dysplasia is graded as _, and what are its involvement?
Low grade - involves the lower portion of the epithelium
High grade - involves the entire layer of the epithelium
Dysplasia may not develop into malignancy. T/F
True.
It may not develop into malignancy if there is an early diagnosis and early treatment. If diagnosis and/or treatment is late, it may develop into malignancy.
When abnormality of the cells involves the entire thickness (or almost the entire layer of the epithelium), it will now become ____.
High grade dysplasia
If cell abnormality incorporates all the layers of the epithelium (or full thickness of the epithelium) and there’s no invasion of the basement membrane, it will now be called
Carcinoma in situ
Once basement membrane is breached, it will now become
Invasive carcinoma
The problem with a transformed cell is that it will not be under the tight regulation of the cells because once the tumor is malignant, it becomes a cancer cell and it will now have an ___
Autonomous growth
What lengthens as tumor grows?
Doubling time of tumor cells
Tumor cells actually needs ________for the cell to become space occupying lesion
10 more doublings ([1kg] lethal burden)
30 doublings (?) = ?
30 doublings (10^9 cells) = 1g
Fraction of tumor cells in replicative pool
- May be only 20% even in rapidly growing tumors
- Tumor stem cells
Rate / cellular processes at which tumor cells
are shed or lost
- Apoptosis (when cells signal the arrest/suicide of these tumor cells)
- Maturation (cancer cells are unable to grow further)
The rate of the tumor growth may be loss or it will stabilize, otherwise the tumor cells will cease to grow. T/F
False,
… tumor cells will continue to grow until it becomes very very big
The bigger the tumor, the chances of invasion and metastasis will be increased. T/F
True
Transformed cell will divide forming this genetically abnormal cells; these are ?
Clone cells
In sun exposure, what causes injury to the DNA of the cell?
Ultraviolet radiation (basis for skin cancer)
___ tend to be prone to develop skin cancer compared to ___
Caucasians ; blacks / heavily pigmented people
Blacks have low incidence of melanoma, so do normally pigmented areas like ___ on white people
Areola
Geographic and environmental factors that may promote tumor growth
- Sun exposure
- Smoking and alcohol abuse
- Body mass
- Environmental vs. Racial factors
- Viral exposure
Overweight = __% increase in cancer
50%
For females, there’s an increased risk of ____, while for males, there’s an increased risk of ___
Breast cancer; prostate cancer
What plays a role in breast carcinoma
Testosterone and estrogen
What plays a role for the growth of prostatic carcinoma
Testosterone
There are also viruses that are ___, example pf this viruses include ___ which causes a cancer of uterine cervix
Oncogenic; Human Papillomavirus (HPV)
Hepatitis B virus (HBV) causes ?
________ causes burkitt’s lymphoma and nasopharyngeal carcinoma
Human Herpesvirus-8 causes ?
Liver cancer
Epstein-Barr virus (EBV)
Kaposi’s sarcoma
Diet high in nitrates can be converted to ___ which is a risk factor for ? cancer
Nitrosamines ; colon cancer
Japanese immigrants now in japan has a diet that is heavily composed of _____. Thus most of the cancers associated with the japanese are ____, followed by liver, colon, and prostate
Fish; stomach
Americans has a diet heavily composed of ____. Thus, Japanese immigrants that now live in USA will show a decrease in ____ and an increase in ___.
Meat; decrease in stomach cancer; increase in colon cancer
Most cancers occur in the elderly aging ___, however there are also childhood malignancies like ____ and ___
> (and equal to) 55 years ; leukemias & CNS neoplasms ; and bone tumors
There’s a familial transmission of these genetic abnormalities
Genetic predisposition
What explains the differences in the genetic constituencies among closely related individuals?
Ex: 2 brothers who smoke heavily, one developed cancer later on but the other one did not. What explains this phenomenon?
Genetic polymorphism
- since they’re brothers, they have difference in their genes that will encode certain enzymes. These enzymes may convert a potential carcinogen to a non-carcinogenic substance. Thus, the other brother may have this gene (which encodes the enzyme) while the one brother that developed cancer may lack this gene.
Hydrocarbons from smoke can be converted to ___ which can cause lung cancer
Epoxides
Early age at onset; two or more primary relatives with the cancer; multiple or bilateral tumors
Familial cancer syndromes
Nonhereditary predisposing conditions
- Chronic inflammation (causes the growth of malignancies)
- Precancerous conditions
Precancerous conditions in nonhereditary predisposing conditions
- Chronic ulcerative conditions / Crohn’s disease (causes colonic cacinoma)
- Atrophic gastritis of pernicious anemia
- Leukoplakia of mucous embranes
Hepatitis B can cause liver cirrhosis which can be a harbinger for
Hepatocellular carcinoma
Tumor cells do not necessarily proliferate at a faster rate than their normal counterparts. T/F
True
Major determinant of tumor growth is ?
More cells produced than die in a given time
Time taken for number of cells in mass to double
Doubling time
Detectable size for mass to be palpable?
30 doubling time
- 1.0 cm^3 (1.0 g) = 10^8 to 10^9 cells = doubles 30x
Tumor is palpable around ?
When is it not palpable?
2cm = palpable
<2cm = not palpable
___ can be employed to detect mass lesion
Imaging studies like CT scan, X-ray, MRI
Sprouting of new capillaries from pre-existing blood vessels; requirement for continued growth of cancers
Tumor angiogenesis
Absence of blood vessels indicate
Tumors grows no larger than 1-2 mm in diameter
Tumor will not grow unless they are fed by new blood vessels because these tumors needs nutrients. T/F
True
Tumors will secrete _____ particularly _____ which enhances the formation of small blood vessels.
Growth factors ; Angiogenic factors
Small blood vessels will nourish the growing tumor. T/F
True
Angiogenic factors (7)
- FGF (Fibroblasts Growth Factor)
- TNF-a (Tumor Necrosis Factor alpha)
- EGF (Epidermal Growth Factor)
- VEGF (Vascular Endothelial Growth Factor)
- TGF (Transforming Growth Factor)
- PDGF (Platelet-derived Growth Factor)
- Angiogenin
Cell proliferation is balanced by apoptosis in the absence of tumor angiogenesis; or may be due to cell cycle arrest
Tumor dormancy
Unregulated growth of cancer cells results from sequential acquisition of somatic mutations in genes that control and differentiation or that maintains the integrity of the genome. T/F
True
Hereditary predisposition
Concept of cancer gene
In cancer gene, there is a presence of chromosomal abnormalities in neoplastic cells. T/F
True
In cancer gene, there is a correlation of _ and _
Impaired DNA repair and occurrence of cancer
In the concept of cancer gene, there is a close association between _ and _
Carcinogenesis and mutagenesis
Most common mechanism of mutagenesis relates to
Spontaneous errors in DNA replication and repair
Genes involved in the pathogenesis of cancer:
- Oncogenes
-Tumor surpressor genes - Mutator genes
These are positive effectors of neoplastic phenotype
Oncogenes
Genes wherein there is loss of function will permit unregulated cell growth
Tumor suppressor genes
The inactivation of this genes will allow further mutations
Mutator genes
Alteration in structure of protooncogene results in
Abnormal gene product
- change in nucleic acids sequence by point mutation, deletion, chromosomal translocation which leads to the synthesis of mutant protein that functions abnormally
Increase in expression of protooncogenes causes
Overproduction of normal gene product
- increased transcription occurs insertional, mutagenesis, chromosomal translocation, and gene amplification
Example of activation by mutation wherein there is a point mutation in codon __ resulting in substitution of _
C-RAS in bladder cancer : point mutation in codon 12 = valine to glycine
- because of the point mutation, C-RAS is activated resulting in urinary bladder cancer
Example of Activation by Chromosomal Translocation wherein it is found in 95% of Chronic Myelogenous Leukemia.
Philadelphia chromosome
In Philadelphia chromosome, ____ on chromosome 9 translocated to chromosome 22 where it is placed in juxtaposition to a site known as ___, wherein an aberrant protein with very high kinase activity is coded
C-ABL Protooncogene; Breakpoint Cluster Region (BCR)
This BCR will ultimately code for an enzyme with a very high kinase activity which will now result or manifested as
Granulocytic hyperplasia (increase in the number of WBCs), a manifestation of Chronic Myelogenous Leukemia
Increase number of gene copies
Activation by gene amplification
____ found in neuroblastoma (a common childhood tumor) or _____ is found in the breast and ovarian cancer.
N-myc protooncogene ; erb protooncogene
Mechanisms of actions of oncogenes (6)
- Extracellular growth factors
- synthesis of PDGF-like factors by neoplastic cells
- Cell surface receptors
- generation of mitogenic signals that override normal control of signaling pathways
- Intracellular signal trandpsduction pathways
- activation of growth factor receptors
- DNA-binding nuclear proteins (transcription factors)
- C-myc activation render cells competent to receive signals for mitosis
- Cell cycle proteins (cycling and cyclin-dependent protein kinases)
- Inhibitors of apoptosis (bcl-2)
Loss of heterozygosity by deletion or somatic mutation predispose to tumor development
Tumor suppressor genes
What happened if the tumor suppressor gene will be subject to mutation?
It becomes defective
Deletion or mutation of tumor suppressor genes enables the damaged DNA to progress through the cell cycle. T/F
True
Most common genetic change in human cancer (deleted or mutated in 80% of cases of colon cancer, frequently in breast cancer, small sell carcinoma of lung, hepatocellular carcinoma, astrocytoma)
Also give its location
P53 gene
Location: small arm of chromosome 17
- protein product of this gene is present in all normal tissues
In P53 gene, mutations allow cells with damage DNA to progress through the cycle. T/F
True
Other tumor suppressor genes:
- _______ - implicated in familial adenomatous polyposis coli and colorectal cancers
- ______ - hereditary Wilm’s tumor
- ______ - neurofibromatosis type 1
- ______ - 90% of pancreatic cancers
- ______ - breast and some ovarian cancers
- APC gene
- WT-1 gene
- NF-1 gene
- DPC-4 gene
-BRCA-1 and BRCA-2 genes
_____ are called _____ which exercise surveillance over the integrity of genetic information by participating in cellular response to DNA damage
Mutator genes ; caretaker genes
Loss of these gene functions renders the DNA susceptible to the progressive accumulations of mutation; when these affect protooncogenes or tumor suppressor genes, cancer will result
Mutator genes
It is estimated that ____ are responsible for 15% of all human cancers
Viral infections
The strongest association of viruses and human cancer includes:
- HTLV-1 virus = T-cell leukemia and Lymphoma
- HPV = squamous cell carcinoma of the cervix
- HBV = hepatocellular carcinoma
- EBV = Burkitt’s lymphoma and Nasopharyngeal carcinoma
- HHV-8 = Kaposi’s sarcoma
Hepatitis B virus > chronic hepatitis > ________ > _______
Liver cirrhosis > liver cancer
______ are proven by epidemiological studies and animal studies
Chemical carcinogen as mutagens
An agent that can permanently alter the genetic constitution of a cell
Mutagen
About 90% of known carcinogens are mutagenic, and all mutagens are carcinogenic. T/F
False,
Most (not all) mutagens are carcinogenic
Many compounds known to be potent carcinogens are relatively _____ in terms of chemical reactivity; most require _______ before they can react with cell constituents
Inert ; metabolic activation
Is a short-term laboratory test done on _______ wherein you will expose this bacteria to these particular chemicals and look for mutations in the genetic material of the bacteria.
It is a test for potential mutagenic capacity of these chemicals
AMES test ; Salmonella typhimurium
4 stages of chemical carcinogenesis
- Initiation - mutations in a single cell
- Promotion - characterized by clonal expansion of the initiated cell
- Progression - growth becomes autonomous; cancer is independent of the carcinogen or promoter; instability of the genome with the end result of further clonal expansion
- Cancer - result when cells acquire the capacity to invade and metastasize
Are inherently reactive to bind covalently to cellular macromolecules. E.g., ______
Direct acting carcinogens ; benzyl chloride
________ through enzymatic reactions effected by cellular systems
- ex: __________ to epoxides (cigarette smoke -> lung cancer)
- aromatic amines and azo dyes converted to _____ (aniline dyes -> _____)
Conversion to a more reactive compound
- polycyclic aromatic hydrocarbons
- hydroxyl derivatives ; bladder cancer
Bronchogenic carcinoma is a relatively common phenomenon because of
Increased smoking cigarettes
Cancers attributed to sun exposure, due to ____, namely:
- Basal cell carcinoma
- Squamous cell carcinoma
- Melanoma
______ are not prone to skin cancer but _____ show increased cases of skin cancer
Blacks / heavily pigmented people with more melanin content ; Caucasians
Carcinogenic effects of UV radiation occurs at wavelength of
290nm to 320nm
Effects of uv radiation in cells include
Enzyme inactivation, inhibition of cell division, mutagenesis, cell death, and cancer
Most important biochemical effect of UV radiation is the _______________ which distorts the backbone of the DNA helix (unless repaired, this genomic injury is mutagenic and carcinogenic)
Formation of pyramidine dimers on DNA
Material widely used in construction, insulation, and manufacturing
Asbestos
Characteristic tumor associates with asbestos is
Malignant mesothelioma of the pleura and peritoneal cavities
These small fibers can cause changes in the cells lining the lung cavity
- ‘Serpentine’ - chrysotile
- ‘Amphiboles’ - crocidolite and amosite
In the ____, asbestos has been banned as a construction material but there is a long latent period of about _____ between exposure and appearance of tumor
1970s ; 20years
Most common cause of death associated with malignancy
Lung cancer
Followed by prostate / breast, colon, stomach, liver, and leukemia
What are usually detected late in the clinical course
Lungs, prostate, and colon
Cause of cancer in males and females:
M: Lungs, prostate, and then colon
F: Lungs, breast, and then colon
