Neoplasia Flashcards
What is the difference between a tumor and neoplasia?
A tumor is a swelling
Neoplasia is a new growth –> cancer is a subset of neoplasia
What is the definition of neoplasia?
A tumor or overgrowth resulting from purposeless proliferation or intrinsically derived abnormal cells
What is the actively growing portion of a tumor called?
parenchyma
What is the difference between dysplasia and anaplasia?
Dysplasia is an abnormality of development or an epithelial anomaly of growth and differentiation
Anaplasia is a condition of cells in which they have poor cellular differentiation.
What is the difference between positional and cellular anaplasia?
Positional- cells are morphologically normal but have abnormal relationships to one another
Cellular- individual cells show structural abnormalities and from each other
What is a key feature seen in aplastic cells?
hyperchromasia–> darker staining of nuclei
Name four biological behaviors of tumors
1) shorter doubling time
2) necrosis
3) invasion
4) metastasis
What is Carcinoma in Situ (CIS)?
malignant epithelial cells with cytologic anaplasia have not yet broken through the barrier of the associated basement membrane
What are the four routes of metastasis?
1) hematogenous spread
2) lymphatic spread
3) Serosal spread–> may cross natural passages (pleural or peritoneal spaces)
4) mechanical implantation
What is neoplastic transformation?
When the DNA of a cell is “garbled” usually effecting cellular reproduction and/or cell death –> leads to immortal cells
defined by autonomous, dysregulated proliferation
What is an adenoma?
A benign epithelial neoplasm with glandular or secretory characteristics (example: adrenal adenoma)
What is a papilloma?
A benign epithelial neoplasm resulting from a multilayered epithelium projecting above the surface of the normal epithelium (example: wart)
What is a polyp?
A benign epithelial neoplasm protruding from a secretory surface
What is a carcinoma?
A malignant epithelial neoplasm
What is a sarcoma?
A malignant stromal neoplasm
What is a lymphoma?
malignant tumors of the lymphoid tissue
What are tertomas?
tumors derived from germ cells, usually found in the gonads. may be malignant or benign
What are the three most common fatal cancers in the US for men and women?
Men–> lung, prostate, colon/rectum
women –> lung, breast, and colon/rectum
What is the most common way for a cancer patient to die?
infection due to suppressed immune systems (happens with or without chemo)
What are paraneoplastic syndromes?
some tumors produce atypical substances or hormones that can have an effect upon the host–> not related to invasion or metastasis
What is tumor grading?
how undifferentiated the cells are microscopically –> defined by pathologist
what is tumor staging?
How far the tumor has spread. Defined by clinician
What is the initial event in the development of cancer?
nonlethal genetic mutation –> mutation of DNA
What is the clonal evolution model of tumorigenesis?
tumors start out monoclonal in origin, but they become very heterogeneous as multiple cells acquire different mutation with time
What is the most vulnerable stage of the cel cycle?l
The S phase (replication)
What are the four principal targets of genetic damage that lead to cancer?
1) DNA repair genes (inactivate)
2) oncogenes (activate)
3) tumor suppressors (inactivate)
4) cell survival genes (activate)
What are the 7 molecular features of cancer?
1) the acquisition of self-sufficiency in growth signals
2) insensitivity to growth inhibitory signals
3) evasion of apoptosis
4) limitless replicative potential
5) sustained angiogenesis
6) tissue invasion and/or metastasis
7) defect in DNA repair–> genomic instability
What are cellular oncogenes?
Structural mutations in these genes or their promoters leads to increased function or over-expression
What are viral oncogenes?
genetically altered proto-oncogenes found in retroviruses that can lead to tumors and transformation. Not currently found in humans
What are the 5 functional classes of oncogenes and list an example of each
1) Growth factors- Platelet derived growth factor is a potent mitogen that leads to astrocytoma and osteosarcoma
2) Growth factor receptors-PDGF and EGF receptors
3) signal transducing proteins- ras signalling (mutated GTPase)
4) Nuclear transcription factors- c-myc leading to Burkitt’s lymphoma and neuroblastoma
5) proteins involved in regulating the cell cycle- CDKs and cyclins (D)
Describe the pathogenesis of Burkitt’s lymphoma?
It is the result of a chromosomal translocation in a mature B cell so that it produces lots of c-myc
Describe the pathogenesis of mantle cell lymphoma?
It is the result of a chromosomal translocation in B cells so that lots of cyclin D exists in the cell keeping in the replicative phase.
Describe the pathogenesis of follicular lymphoma?
It is the result of a chromosomal translocation in B cells resulting in overexpression of BCL2 –> an antiapoptosis gene
What are the 5 mechanisms by which oncogenes become activated?
1) mutational activation (frameshift, point…)
2) chromosomal translocation
3) Transcriptional activation
4) Epigenetics
5) microRNAs
What is the function of the retinoblastoma gene product?
It is a tumor suppressor. It is normally hypophosphorylated and binds to transcription factor, E2F, keeping it in its inactive form. Cyclin D phosphorylates retinoblastoma and it separates from E2F which can then go on to increase transcription in the S phase.
Inherited mutation of p53 result in which disease?
Li-Fraumeni syndrome
What is the function of p53?
It is a tumor suppressor that prevents the propagation of genetically damaged cells. It is activated when a cell is mutated and it up regulates p21 which induces cell cycle arrest in G1 and up-regulates GADD45 which is a repair gene that attempts to fix the damage. If it cannot be fixed p53 up-regulates bax which causes apoptosis.
If p53 is damaged in a tumor what would NOT be a good therapy?
radiation
What are 5 characteristics of tumor suppressor genes?
1) Recessive at the cell level (loss of function)
2) tissue specificity
3) germline inheritance frequently leads to cancer
4) No known analogues in oncogenic viruses (in humans)
5) Germline mutations may initiate, but mutation to neoplasia only occurs during progression
What 3 things can inactivate a tumor suppressor?
1) DNA mutations
2) epigenetic changes
3) microRNAs
What are the proapoptotic proteins?
Bax, Bak, Bid and Bim
What are the antiapoptotic proteins?
Bcl-2, Bcl-XL, Bcl-W
What are the three general classes of signaling factors that mediate angiogenesis?
1) soluble factors and their receptors –> VEGF and fibroblast growth factors
2) integrins and adherins
3) extracellular proteases
What classes of molecules are involved in metastasis and tissue invasion?
1) cell-cell adhesion molecules like CAMs, cadherins, and inegrins
2) extracellular proteases like MMps
What is the Warburg Effect?
Most cancers shift glucose metabolism and ATP production away from mitochondria to aerobic glycolysis –> used in PET scanning
Describe some key features of the initiation phase of the multistage model of carcinogenesis
occurs in single cells
irreversible
dose dependent
usually involves a single mutational event
Not all initiated cells go on to become cancer
Describe some key features of the promotion phase of the multistage model of carcinogenesis
reversible
exogenous signaling that is usually receptor mediated
has a detectable dose response and threshold
increases proliferation or decreases apoptosis
Describe some key features of the progression phase of the multistage model of carcinogenesis
irreversible
acquisition of multiple mutations often resulting in genomic instability
What are some examples of autosomal dominant monogenetic inheritance?
retinoblastoma, p53 and APC (familial adenomatous polyposis coli)
What are some examples of autosomal recessive monogenic inheritance?
DNA repair genes that result in disorders like ataxia telangiectasia and xeroderma pigmentosa
T/F most inherited cancers are monogenic
FALSE. polygenic
What is a procarcingogen?
a chemical substance that becomes a carcinogen only after it is altered by metabolic processes (becomes an electrophile)
What examples of procarcinogens?
polycyclic aromatic hydrocarbons (tobacco and animal fats)
Aromatic amines and azo dyes like b-naphthylamine–> bladder cancer
Aflatoxin B1–> hepatocellar carcinomaq
What kind of cancers does EBV lead to?
Burkitt’s lymphoma
Nsopharyngeal carcinoma
some Hodgkins and some B cell lymphoma
What kind of cancers does HBV lead to?
hepatocellular carcinoma
What kind of cancers does herpes virus 8 lead to?
karposi sarcoma
What kind of cancers does HTLv1 and 2 lead to?
T cell leukemia/lymphoma
What kind of cancers does helicobacter pylori lead to?
gastric carcinoma
MALT lymphoma
What kind of cancers does schistosoma hematobium lead to?
bladder cancer
What kind of cancers does opisthorchis viverrini lead to?
hepatic cholangiocarcinoma (bile duct epithelium)