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173 Cards in this Set
- Front
- Back
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what is G6PD?
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an enzyme present on the x-chromosome
want to keep a 1:1 ratio of G6PD isoforms in hyperplasia; because all tumor cells are derived from one cell in neoplasia, only one isoform will be expressed so this is how you can prove a growth is neoplasia rather than hyperplasia |
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how can clonality be determined by Ig light chain phenotype?
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light chain will either be kappa or lambda in a 3:1 ratio; if one cell expands than ratio may grow to 20:1
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what is a benign tumor from the epithelium? (2)
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adenoma (glands)
papilloma |
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what is a malignant tumor from the epithelium? (2)
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adenocarcinoma
papillary carcinoma |
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what is a benign tumor from the mesenchyme?
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lipoma
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what is a malignant tumor from the mesenchyme?
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liposarcoma
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what is a malignant tumor from a lymphocyte?
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lymphoma/leukemia
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what is a benign tumor from a melanocyte?
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nevus (mole)
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what is a malignant tumor from a melanocyte?
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melanoma
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what is a benign tumor from fibrous cartilage?
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fibroma
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what is a malignant tumor from fibrous cartilage?
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fibrosarcoma
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what is a benign tumor from cartilage?
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chondroma
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what is a malignant tumor from cartilage?
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chondrosarcoma
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what is an adenomatous polyp?
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a colon polyp composed of a proliferation of glands with some intervening stroma
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what is a polyp?
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raised lesion that grows outward from a mucosal surface
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what is a tumor of neuroendocrine cells that produces many hormones?
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small cell carcinoma
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what is the replacement of one cell type with another?
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metaplasia
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what is always found in association with tissue damage and repair?
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metaplasia
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what may lead to dysplasia?
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metaplasia
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what is disorganized growth?
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dysplasia
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what is it called when there is some loss of polarity?
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dysplasia
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what is it called when dysplastic changes involve the full thickness of the epithelium?
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carcinoma in situ
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what is considered to be a preinvasive cancer that will eventually progress to an invasive carcinoma?
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carcinoma in situ
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how many cell divisions must occur before the earliest symptoms of cancer arise?
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30
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is dysplaisa reversible?
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yes
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what type of cancer will aflatoxins from aspergillis cause?
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hepatocellular carcinoma
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what type of cancer will alkylating agents cause?
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leukemia/lymphoma
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what type of cancer will alcohol cause? (2)
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squamous cell carcinoma of oropharynx
pancreatic carcinoma |
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what type of cancer will arsenic cause? (2)
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squamous cell carcinoma of skin
lung cancer |
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what type of cancer will asbestos cause? (2)
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lung carcinoma
mesothelioma |
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what type of cancer will cigarette smoke cause? (5)
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oropharynx
esophagus lungs kidney bladder |
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what type of cancer will nitrosamines cause?
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stomach cancer (especially in japan)
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what type of cancer will napthylamine cause?
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urothelial carcinoma of the bladder
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what type of cancer will vinyl chloride (PVC pipes) cause?
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angiosarcoma of the liver
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what type of cancer will nickel and chromium cause?
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lung cancer
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what encodes for an enzyme involved in the metabolism of polycyclic hydrocarbons?
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CYP1A1
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what will a mutation in CYP1A1 cause?
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increased inducibility of the enzyme metabolizing polycyclic hydrocarbons which then increases their activation in the lungs
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what is an oncogenic virus associated with nasopharyngeal carcinoma?
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EBV
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what is an oncogenic virus associated with Burkitt lymphoma?
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EBV
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what is an oncogenic virus associated with CNS lymphoma in AIDS?
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EBV
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what is an oncogenic virus associated with B cell lymphoma?
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EBV
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what 2 genes are responsible for the transforming effects of EBV?
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LMP1 and EBNA2
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what gene acts as a constitutive CD40 receptor, stimulating cells to proliferate and promote survival?
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LMP1 in EBV
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what gene upregulates cyclin D and other protooncogenes?
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EBNA2 in EBV
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what oncovirus is associated with kaposi sarcoma?
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HHV8
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what is manifested as purple, raised lesions on the skin that is more common in older eastern European males and AIDS patients?
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kaposi sarcoma
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what oncovirus is associated with hepatocellular carcinoma? (2)
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HBV and HCV
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what oncovirus is associated with adut T cell lymphoma and leukemia?
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HTLV1
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what oncovirus is endemic in Japan and Carribean?
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HTLV1
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what oncovirus is transmitted via needles, blood, sex, and breast feeding?
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HTLV1
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what oncovirus is associated with squamous cell carcinoma of the vulva, vagina, anus, and cervix?
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HPV
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how does HTLV1 transform cells?
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through the tax gene which activates transcription of several host genes involved in T cell proliferation and inacitvates p16/INK4 to interfere with DNA repair
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what does the tax gene do?
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activated several host genes involved in t cell proliferation in HTLV1
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what does p16/INK4 do?
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responsible for DNA repair; inactivated in HTLV1
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how does HPV transform cells?
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results in the loss of HPV E2 and overexpression of HPV E6 and E7
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what bacteria is associated with gastric adenocarcinoma?
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H pylori
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what gene in H pylori gets constitutively activated and what does it do?
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CagA
growth factor signal transductase pathway |
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what cancers does ionizing radiation cause? (3)
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AML
CML papillary carcinoma of the thyroid |
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what cancer is cystitis associated with?
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bladder carcinoma
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what cancer is ulcerative colitis associated with?
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colon cancer
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what cancer is reflux esophagitis associated with?
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esophageal carcinoma
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what cancer is gastritis associated with (2)?
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gastric carcinoma
MALT lymphoma (low grade B cell lymphomas) |
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what cancer is lichen sclerosis associated with?
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vuvlar carcinoma
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what are the epidermal growth factors that are amplified in breast carcinoma?
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ERBB2/Her2Neu
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what are the epidermal growth factors that are associated with squamous cell carcinoma of lung?
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ERBB2/Her2Neu
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what is the neural growth factor receptor that gets overexpressed in sporadic medullary carcinoma of the thyroid?
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RET (due to a point mutation)
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If RET undergoes gene rearrangement, what will it result in?
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papillary thyroid carcinma
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how are papillary thyroid carcinoma and sporadic medullay carcinoma of the thyroid related?
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both are due to mutations in the RET gene
papillary thyroid carcinoma = gene rearrangement sporadic medullary carcinoma of the thyroid = point mutation |
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what signal transducer undergoes a point mutation and results in neurofibromatosis?
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RAS
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what signal transducer undergoes a point mutation and results in carcinoma?
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RAS
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what signal transducer undergoes a point mutation and results in melanomas?
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RAS
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what signal transducer undergoes a point mutation and results in lymphomas?
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RAS
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what is the oncogene that gets overexpressed in astrocytoma?
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platelet derived growth factor
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what is ABL?
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a tyrosine kinase
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what kind of mutation does ABL undergo and what does it result in?
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9:22 translocation
CML & AML |
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what does RAS become insensitive to that makes is constantly activated?
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GAP
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what is CCND1?
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a cyclin
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what kind of mutation does CCND1 undergo and what does it result in?
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11:14 translocation involving IgH
results in a mantle cell lymphoma |
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what is INK4a/ARF?
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a cyclin dependent kinase
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what kind of mutation does INK4a/ARF undergo and what does it result in?
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silencing
results in cervical carcinoma |
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what kind of mutation does CDK4 undergo and what does it result in?
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amplification
melanoma |
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what are 3 key transcription factors that can be mutated?
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C-MYC, N-MYC, L-MYC
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what kind of mutation does C-MYC undergo and what does it result in?
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11:14 translocation involving IgH
Burkitt lymphoma |
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what is the hallmark of burkitt lymphoma?
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starry cell appearance
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what kind of mutation does N-MYC undergo and what does it result in?
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amplification
neuroblastoma |
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what kind of mutation does L-MYC undergo and what does it result in?
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amplification
lung carcinoma |
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what are chromosomal deletions associated with?
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loss of tumor suppressor genes
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what will a 13q14 deletion result in?
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retinoblastoma
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what will a 17p, 5p, and 18q deletion result in?
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colorectal carcinoma
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what will a 3p deletion result in? (2)
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small cell lung cancer
renal cell carcinoma |
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what portion of the cell cycle does p53 regulated?
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G1 --> S
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if repair is not possible, what does p53 do?
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induces apoptosis via BAX
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what is LiFraumeni syndrome?
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germline mutation of p53
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in tumors that do not have a p53 mutation, what do they have?
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a mutation in MDM2, something that regulated p53 by marking it for degradation
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what type of treatment are malignant neoplasms with p53 mutations resistant to?
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chemo and irradiation
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what part of the cell cycle does Rb regulate?
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G1 --> S
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how does Rb work?
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"holds" E2F; E2F is released when Rb is phosphorylated
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where is the Rb mutation found?
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Rb pocket
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what will a sporadic Rb mutation result in?
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unilateral retinoblastoma
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what will a germline Rb mutation result in? (2)
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bilateral retinoblasoma
osteosarcoma |
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what is a membrane associated phosphatase that serves as a brake on the P13/AKT pathway?
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PTEN
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how does PTEN work?
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cleaves PO4 from PIP3
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what will germline mutations in PTEN lead to?
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Cowden syndrome with benign skin lesions and juvinille GI polyps
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what is cowden syndrome?
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benign skin lesions and juvenille GI poylps due to germline mutations in PTEN
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what will somatic mutations in PTEN lead to? (5)
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breast, prostate, thyroid, and endometiral carcinomas
gliomas |
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what is TGF-beta?
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a potent inhibitor of proliferation via phosphorylation of CDKIs
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What will be mutated in 100% of pacreatic cancers and 83% of colon cancers?
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TGF-beta
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what are 2 components of the TGF-beta pathway that act as tumor suprpessors?
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SMAD2 and SMAD 4
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what is overexpressed in a majority of colon cancers?
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COX-2
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what 2 molecules mediate the extrinsic pathway?
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FasL, FADD, FLIP
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A decrease in expression of this will render tumor cells less susceptible to apoptosis
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Fas
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What is normally stabilized in the mt membrane, blocking the release of cytochrome C?
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Bcl2 (so when Bcl2 is there is prevents apoptosis)
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what type of mutation occurs with Bcl2 and what will it result in?
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14:18, Bcl2 becomes over expressed
follicular lymphoma |
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how can tumor cells evade immune survailance?
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down regulate MHC1
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what 2 factors are produced by tumor cells to promote angiogenesis?
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FGF & VEGF
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what is the Warburg effect?
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when cancer cells shift their glucose metabolism away from oxidative phosphorylation to aerobic glycolysis
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what ag is over expressed in some melanomas?
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tyrosinase
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what is MAGE normally expressed in and what cancer is it found in?
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normally in testis
expressed in melanomas |
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what proteins are expressed at high levels in cancer cells and fetal tissue?
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alpha feto-protein
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what often expresses gangliosides GM2 and GD?
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melanomas
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what often overexpresses CA-125?
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ovarian carcinomas
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what often overexpresses CA-19-9
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pancreatic carcinomas
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what cancer is positive for CD20?
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b cell lymphomas
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what are epigenetic changes?
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heritable, reversible changes in gene expression that occur without mutations via DNA methylation of histone modifications
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how can the tumor suppressor gene p21 be repressed via epigenetic changes?
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over expression of EZH2 places repressive chromatin marks at the promoter of the p21 gene
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what is over expresses in breast and prostate cancers?
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EZH2 which represses the p21 tumor suppressor
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how can micro RNAs lead to cancer?
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bind to complementary sequences on target mRNAs and block translation of the target mRNA which leads to gene silencing
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in what cancers do miRNAs have decreased expression (and what will this result in an increased expression of?) (2)
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decreased miRNA expression in some leukemias and lymphomas (thus increased BCL2 expression)
decreased miRNA expression in some lung cancers (thus increased RAS expression) |
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what will cells down regulate in order to metastitcize?
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E cadherin
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what type of cancers have a high growth fraction and what type of treatment do they respond best to?
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leukemias and lymphomas
chemo |
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what is the growth fraction?
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number of tumor cells that are in the proliferative pool
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what cancers have a low growth fraction?
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colon and breast cancer
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how do you treat cancers with low growth fraction?
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shift tumor cells from G0 into the cell cycle by removing a lot with surgery or radiation
the surviving cells then enter the cell cycle and become susceptible to chemo |
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will most cells be in the proliferative pool by the time a tumor is detected?
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no
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what type of spread is characteristic of carcinomas?
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lymphatic spread
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what type of spread is characteristic of sarcomas?
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hematogenous
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what does a renal cell carcinoma use to spread?
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renal cell carcinoma
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what does a hepatocellular carcinoma use to spread?
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hepatic veins
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what is the most common cancer to spread to the vertebral vein
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protstate cancer
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what cancer is known for seeding of body cavities and "omental caking"?
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ovarian carcinoma
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what do breast cancers express that increase metastasis to lymph nodes?
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CXCR4
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how do drugs that block CXCR4 work?
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block CXCR4 binding thus decreasing metastasis to lymph nodes
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what results from a defect in DNA mismatch repair creating characteristic microsatellite instability leading to frameshift mutations?
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HNPCC
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what is mutated in breast cancer that results in a mutation in homologous DNA repair?
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BRCA1 and BRCA2
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what is a normal nuclear:cytoplasmic ratio and what is it in cancer?
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normal = 1:4
malignancy = 1:1 |
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in immunohistochemistry, what will keratin show?
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epithelium (carcinoma)
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in immunohistochemistry, what will vimentin show?
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mesenchyme (sarcoma)
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in immunohistochemistry, what will desmin show?
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muscle
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in immunohistochemistry, what will GFAP show?
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neuroglia
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in immunohistochemistry, what will neurofilaments show?
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neurons
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PSA is an indicator for
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prostatic epithelium
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ER is an indicator for
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breast epithelium
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thyroglobulin is an indicator for
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thyroid follicular cells
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chromogranin is an indicator for
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neuroendocrine cells (eg small cell carcinoma of the lung and carcinoid tumors)
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S-100 is an indicator for
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melanoma
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alpha feto-protein is an indicator for (2)
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hepatocellular carcinoma
nonseminomatous germ cell tumors of the testis |
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CA-15-3 is an indicator for
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breast carcinoma
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what are serum tumor markers?
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proteins released by tumors
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what does grading of a cancer determine?
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the differentiation of the cells
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what is a well differentiated tumor?
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resembles the parent tissue
good prognosis |
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what is the hallmark of malignany?
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anaplasia, lack of differentiation
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what is staging of cancer based on?
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shape and size
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what is the key prognostic factor for cancer?
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its stage, not grade
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what is TMN staging?
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T = tumor size or depth of invasion
N = spread to regional lymph nodes; second most important prognostic factor M = metastasis; single most prognostic factor |
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what is cancer cachexia?
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progressive loss of body fat, lean body mass, weakness, anorexia
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what is cancer cachexia believed to be caused by?
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mediators (cytokines, proteolysis inducing factors, lipid metablozing factors)
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what is cushings syndrome due to?
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small cell carcinoma of the lung and ACTH
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what is hypercalcemia due to?
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squamous cell carcinoma of the lung and PT related to H
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what is polycythemia due to?
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renal cell carcinoma and erythropoitin
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what is trousseau syndrome?
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migratory thrombophlebitis
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what is trosseau syndrome due to?
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pancreatic adenocarcinoma and mucins that acitvate clotting
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what is autoimmune hemolytic anemia due to?
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lymphoma and antiRBC antibodies
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what is acanthosis nigricans due to?
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adneocarcinoma of the GI tract and TGF-alpha
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