Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
90 Cards in this Set
- Front
- Back
Importance of Glucose-6-phosphate enzyme isoforms?
|
Clonality can depict neoplasm. Normally women inherit an X-linked G6PD isotype from each parent. The ratio of each type should be 1:1. If it's asymmetrical you have a monoclonal growth that can indicate a neoplastic growth. Theoretically any X-linked isoform would work, so if androgen receptors have isotypes you could use those instead. X-linked and thus ONLY WORKS ON WOMEN
|
|
B cell clonality determined by Ig light chain phenotype
|
Ig has 2 heavy, 2 light chains each b cell expresses light chains that are either kappa or lambda
the NORMAL ratio is 3:1 kappa to lambda any extreme asymmetry from this ratio could indicate neoplasm |
|
3:1 ratio represents?
|
3 Kappa light chains to 1 LAMBDA Light chain
|
|
Enlarged lymph node DDx
|
Metastatic Cancer
Reactive hyperplasia due to infection Lymphoma DIAGNOSTIC FOR LYMPHOMA is a Kappa to Lamda ratio that is NOT 3:1 |
|
Lamda to Kappa ratio of 3:1 and enlarged lymph node
|
LYMPHOMA b/c should be 3:1 K:L
|
|
Kappa to Lamda ratio of 3:1 and enlarged lymph node
|
NORMAL
|
|
Aflatoxin
|
hepatocellular carcinoma, produced by Aspergillus which can contaminate stored grains
|
|
history with a grain silo
|
Aspergillus, can make aflatoxins which cause hepatocellular carcinoma
|
|
Alkylating agents
|
Leukemia/lymphoma this can be a side effect of chemotherapy
|
|
Squamous cell carcinoma of oropharynx and upper esophagus
|
alcohol
|
|
pancreatic carcinoma
|
alcohol
|
|
MCC of hepatocellular carcinoma
|
alcohol
|
|
Carcinogens in cigarette smoke
|
Polycyclic Hydrocarbons, Arsenic, Naphthylamine
|
|
Squamous cell carcinoma of skin risk factor
|
Arsenic - was used as skin whitener
|
|
lung cancer can be caused by this chemical in cigarettes
|
arsenic
|
|
Lung carcinoma
|
Asbestos This is MORE LIKELY than mesothelioma after asbestos exposure
|
|
Mesothelioma
|
asbestos
|
|
Most carcinogenic chemical in cigarette smoke?
|
polycyclic hydrocarbons
|
|
Cigarette smoke causes...
|
Carcinoma of oropharynx, esophagus, lung AND kidney, bladder due to hyperconcentration of carcinogens in urine.
Also, increases likelihood of cervical cancer. |
|
History of eating large amount of smoked foods with Japanese descent
|
Think Nitrosamines Stomach cancer, Intestinal type, NOT diffuse
|
|
Urothelial carcinoma of bladder
|
Naphthylamine (cigarette smoke derivative concentrated in urine)
|
|
What symptom would you expect to see from occupational exposure to Polyvinyl chlorides such as those used to make PVC pipes?
|
Angiosarcoma of the liver caused by the vinyl chloride exposure
|
|
Occupational exposure to Nickel, chromium, beryllium or silica
|
Lung cancer b/c inhaled
|
|
Chinese male or indigenous african presenting with neck mass
|
Nasopharyngeal carcinoma secondary to EBV. Because very early on the tumor metastasizes to local regional lymph nodes
|
|
Cancer associated with EBV
|
Burkitt's lymphoma, nasopharyngeal carcinoma, and CNS lymphoma in AIDS patients
|
|
Older eastern european male and you see a papular erythematous lesion
|
Kaposi Sarcoma (tumor of endothelial cells ->purplish raised lesions on skin) caused by HHV-8. Afflicts AIDS patients, transplant patients (immune system suppressed), older Eastern Europeans males b/c strain in the region more likely to cause KS.
|
|
Which hep viri preclude hepatocellular carcinoma?
|
Hep B and Hep C Hep B = Hepadnavirus Hep C = Flavivirus (RNA virus)
|
|
HTLV-1
|
HTLV-1 (Human T-cell Leukemia Virus-1) is a retrovirus that predisposed to Adult T-cell leukemia/lymphoma
|
|
HPV high risk? low risk?
|
High risk = strains 16, 18, 31, 33 of HPV (Squamous cell carcinoma of lower GU tract (vulva, vagina, anus, cervix). Also ADENOcarcinoma of cervix Low Risk = 6, 11 (condyloma acumulatum-> genital warts caused by 6 or 11HPV)
|
|
A worker during the japanese nuclear meltdown is predisposed to
|
ionizing radiation causing AML, CML and papillary carcinoma (finger like projections covered by epithelial cells with blood vessel running down the middle) of the thyroid
|
|
What is the malignant cell in AML
|
myeloblast - Unipotent stem cell in Bone Marrow that can differentiate into granulocytes (Neutrophil, Basophil, Eosinophyl) and Monocyte/dendritic cell
|
|
What is the MOA of ionizing radiation
|
generation of hydroxyl free radicals that damage DNA as radioactive particles hit water
|
|
MOA of non-ionizing radiation
|
pyrimidine dimers are created which are normally excised by restriction endonucleases
|
|
non-ionizing radiation(UVB light) predisposes to....
a/w? |
Basal cell carcinoma of skin, squamous cell carcinoma of skin and melanoma of the skin
Xeroderma Pigmentosum - base excision is repair via restriction endonucleases is mutated/broken. |
|
Most common cancers of INCIDENCE
|
breast/prostate
lungs colorectal |
|
Most common cancers of MORTALITY
|
lung
breast/prostate colorectal |
|
Mammography looks for which cancer?
|
DCIS, ductal carcinoma in situ - visible because ductal carcinoma proliferates rapidly in ducts of breasts and dies. Calcium binds to necrotic tissue and this calcification is visible on x-ray
|
|
Where does prostate cancer generally present?
|
posterior periphery ->rectal exam works because rectum is posterior to prostate.
|
|
How many divisions does average cancer undergo before becoming symptomatic
|
30. The sooner you catch it, or even better when it is still dysplasia and remove it, the better the chance that it has not yet metastasized.
|
|
Why is lung cancer survival still 15%?
|
There is so much room in the lung that no symptoms (e.g. compression) experienced until >30-40 divisions. Therefore cancer often detected after MANY mutations and it has metastasized.
|
|
Describe the RAS pathway
|
ras-GDP associated with GF in an inactive state
Receptor binding causes GDP to be replaced with GTP activating ras ras sends growth signals to nucleus ras inactivated itself by cleaved GTP to GDP. This is overseen by GTPase activating protein NOW ABNORMALA mutated ras inhibits GTPase activating protein, resulting in its constitutively activation. |
|
Describe role of p53 in DNA repair
|
p53 is the cell cycle cop It stops a cell in G1 going to S and checks the DNA. If its crappy DNA, it'll say to go get fixed. If it can't get fixed, p53 euthanizes the cell via the Bcl pathway. p53's thug, BAX breaks the Bcl2 that stabilizes the mitochondrial membrane, and thus cytochrome c leaks out and activates apoptotic pathways.
|
|
Li-Fraumeni syndrome
|
germline mutation of one p53 gene.
|
|
Rb's role in cell cycle regulation
|
Rb is bound to E2f, this keeps the cell cycle in G1. When CDK comes over and phosphorylates Rb, E2f falls off and gives the green light for S phase and parties like its 1939. If Rb is mutated, then it is NEVER attached to E2f and the cell ALWAYS has the greenlight to party. That's bad
|
|
Germline retinoblastoma is A/w?
|
osteosarcoma
|
|
What gene is overexpressed in follicular lymphoma?
|
Bcl2. This overstabilizes the mitochondrial membrane, which isn't usually a problem except in the thymus, where you need negative selection to get rid of autoreactive t-lymphocytes. Also B-cells that would undergo apoptosis during somatic hypermutation...don't. This leads to lymphoma, which is probably polyclonal.
|
|
Follicular lymphoma is associated with what translocation?
|
t(14;18) moves Bcl2(18) to the Ig heavy chain locus(14) making it constitutively active
|
|
Describe the process of tumor invasion
|
TUMOR INVASION!!
1.) downregulation of E-cadherins, which normally keep cells attached to each other, -> Detachment. 2.) Tumor cells bind to laminin, and in the process destroy the basement membrane (type IV collagen) via collagenase 3.) Attach to fibronectin in the ECM and spread locally 4.) Depending on whether they reach a blood or lymph vessel, they will spread down that route. Lymphatic spread usually moves to lymph node, while hematogenous spread tends to be to distant sites. |
|
Sarcoma's generally spread...
|
haemotogenously - b/c a lot of immediate blood supply. Tumors that spread hematogenously typically reach distant sites.
|
|
Breast cancers initially/most commonly spread...
|
lymphatically b/c closest easiest site for the to reach. Spread to Axillary Lymph nodes and proliferate inside them b/c axillary lymph nodes drain the breast. Lymphatics are usually more accessible to epithelial tumors.
|
|
omental caking
|
ovarian carcinoma. Commonly seeds body cavities, like the peritoneum b/c when breaks through Basement Membrane and ECM, it is in body cavity.
|
|
Epithelial neoplasias that do not spread Lympahtically but rather Hematogenously
|
Typically these neoplasms are near areas of large blood supply.
1) Renal cell carcinoma(invades renal vein) = spreads to distant sites 2) Hepatocellular carcinoma(invades hepatic vein) 3) Follicular carcinoma of the thyroid (follicular cells normally release T3/T4 directly into capillaries that juxtapose them -> lots of nearby blood vessels) 4) choriocarcinoma(placental malignancy) b/c it is a cancer of cells that line villi of placenta (trophoblasts) that are normally programmed to find blood vessels and invade them (this is the job of the placenta after all) |
|
Keratin stains
|
epithelium
|
|
vimentin
|
mesenchyme
|
|
Desmin
|
muscle
|
|
GFAP
|
neuroglia
|
|
neurofilament
|
neurons
|
|
neurons IMF
|
neurofilament
|
|
neuroglia IMF
|
GFAP
|
|
muscle IMF
|
desmin
|
|
Mesenchyme IMF
|
vimentin
|
|
Epithelium IMF
|
Keratin
|
|
S-100
|
Melanin
|
|
What do you look for to be positive in melanoma's?
|
S-100
|
|
Chromogranin
|
Small cell carcinoma of lung and carcinoid tumors both of those are neuroendocrine tumors
|
|
Neuroendocrine tumors
|
Small cell carcinoma of lung and carcinoid tumors
stains Chromogranin |
|
Absolute definition of benign neoplasm
|
Will never metastatize
|
|
CA-125
|
ovarian cancer, NON-specific test
|
|
Single most prognostic indicator?
|
metastasis
|
|
Grade or Staging more important?
|
Staging -- TNM
|
|
Staging or Grade more important?
|
Staging -- TNM
|
|
PDGFB mutation a/w?
|
overexpression, autocrine loop that can lead to an astrocytoma
|
|
breast carcinoma's can sometimes express this receptor
|
ERBB2[HER2/Neu] amplification of receptors expressed.
|
|
Common treatment for ERBB2 cancers
|
Trastuzumab
|
|
RET function
|
neural growth factor receptor
|
|
RET A/W
|
MEN 2A, MEN 2B, sporadic medullary carcinoma of thyroid
|
|
KIT function?
|
Stem cell growth factor receptor
|
|
KIT A/W
|
gastrointestinal stromal tumor
|
|
RAS gene family A/W
|
Carcinomas, melanoma and lymphoma
|
|
ABL
|
Tyrosine kinase
|
|
ABL A/W
|
CML and some types of ALL(poor prognosis)
t(9;22) with BCR. Abl starts on 9, but swaps with BCR which is on 22 |
|
c-MYC A/W
what translocation? |
Burkitt Lymphoma transcription factor
t(8;14) involving IgH (Ig Heavy chain) on chromosome 14, which is always on. So when MYC (transcription factor for growth factors) gene normally found on chromosome 8 is translocated to the IgH location, it becomes constitutively turned on, and problems arise! In the party factory. |
|
N-MYC
|
amplification mutation leading to Neuroblastoma
|
|
L-MYC
|
Small cell lung carcinoma
|
|
CCND1(Cyclin D1)
What translocation? |
Mantle cell lymphoma t(11;14) involving IgH which is always on. So when cyclin, which regulates cell cycle is ALWAYS on, the cops never roll that party.
|
|
CDK4 mutation
|
Melanoma
|
|
Growth Factor Receptors
|
ERBB2[HER2/neu]
RET KIT |
|
Signal Transducers
|
RAS gene family - GTP binding protein
ABL - Tyrosine Kinase |
|
Nuclear Regulators
|
c-MYC
N-MYC L-MYC they're all transcription factors |
|
Cell Cycle Regulators
|
CCND1(Cyclin D1)
CDK4 |