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Path Neoplasia
KYCOM Block 11
202
Pathology
Graduate
10/14/2013

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Term
what are 5 words that describe a neoplastic cell, explain each
Definition
heritable: cused by genetic changes (parent to daughter cell not mom to baby)

clonal: come from single cell

unregulated: loss of response to growth controls

competitive: compete with normal cells for metabolites

non-autonomous: need blood, nutrients, and sometimes hormones
Term
what are 4 signs of a benign tumor
Definition
innocent microscopic characteristics: resembles tissue of origin, well differentiated

localized

growth is slow and can regress or pause

well demacrated
Term
why can a benign tumor be surgically removed
Definition
it is well demacrated
Term
what are 4 characteristics of a malignant tumor
Definition
anaplasia (most of the time)
metastasis
erratic growth
mitotic figures
Term
define anaplasia
Definition
cells without polarity organization
usually loss of differentiation
many abnormal mititoc figures
Term
define metastasis
Definition
can invade adjacent tissue and spread to distant sites in the body
Term
define dysplasia
Definition
disorderly non-neoplastic proliferation usually of epithelia
Term
what are 4 characteristics of dysplasia
Definition
loss of architectural uniformity and cell orientation
pleomorphic
hyperchromatic
carcinoma-in-situ
Term
define pleomorphic
Definition
cells vary in size and shape
Term
define hyperchromatic
Definition
deeply stained nuclei
Term
define carcinoma-in-situ
Definition
dysplasia through entire epithelial thickness but not BM (pre-invasive cancer)
Term
how is dysplasia treate
Definition
reversable if it does not involve entire epithelial thickness
Term
what are the 5 steps in tumor naming
Definition
1. suffix -oma
2. if benign skip to step 4
3. add carcin- if epithelial origin or sarc- if mesenchyma
4. choose a root to describe cell origin
5. if none of the roots fit choose hamartoma or coristoma
Term
what does -oma mean
Definition
swelling
(for neoplasms and non-neoplasms)
Term
name the root for: fibroblasts, myxoid, cartiladge, osteoblasts, fat
Definition
fibro
myxo
chondro
lipo
Term
name the root for: notochord, smooth muscle, striated muscle, perineurium, endoneurium
Definition
chordo
leiomyo
rhabdomyo
schwannao/neurolemmo
neurofibro
Term
name the root for: vessels, lymphatics, glomus, synovium, mesothelium
Definition
hemangio
lymphangio
glomangio
synovio
mesothelial
Term
name the root for: arachnoid granulations, lymphocytes, placenta, adrenal medulla,
Definition
meningio
lympho
chorio
phrochromocyto
Term
name the root for: glandular epithelium, swuamous or transitional epithelium, resemblence of embryonic cells, totipotent cells from germ layers
Definition
adeno
papillo
blasto
terato
Term
what type of root is for a tumor that has hair and teeth
Definition
terato

totipotent cells from germ layers
Term
what is a hamartoma, how can it be identified
Definition
developmental abnormality, not a tumor

contains tissue of origin but in wrong proportions and disorganized
Term
what is a choristoma (ectopia)
Definition
mass of normal tissue in abnormal location
Term
what is the qualification to be considered a carcinogenesis
Definition
must bypass hayflick limit: length of telomerase or telomerase alternative mechanism
Term
what are the two categories of causes of carcinogenesis
Definition
expansion of single progenerator with non-lethal mutation

defect in DNA repair genes are unable to fix a mutation
Term
what are the two types of single progenitor mutations
Definition
germline / inherited
somatic / acquired
Term
what is the problem in hderditary nonpolyposis colon carcinoma syndrome (NHPCC)
Definition
defect in DNA mismatch repair
Term
what is the problem in xeroderma pigmentosum
Definition
defect in nucleotide excision repair
Term
what is the problem in Bloom's, Werner's, and rothmund thomson syndromes
Definition
RecQ helicase mutations
Term
what is the problem in BRCA1/2 mutations
Definition
defect in double strand break repair cases breast cancer
Term
what are the three effects of carcinogenesis, the thee MOA categories of cancer development
Definition
activation of oncogenes (mutant alleles) transforms cells and promotes autonomous cell growth

mutation of growth inhibiting cancer supressor genes (anti-oncogenes)

mutation of genes controlling apoptosis
Term
in general, how do oncogenes cause cancer
Definition
dominant: only one needs to be activated

change gene sequence making new protein that is no longer inhibitory (oncoprotein)

product causes over production of normal proteins
Term
what is an autocrine loop
Definition
when some cancer cells acquire the ability to make the same growth factors they are responsive to so it creates loop that sitmulates the continued growth of the tumor
Term
how do anti-oncogenes work
Definition
mutation of growth inhibitng cancer supressor is recessive so both genes must be damaged
Term
what is an example of dominant mutation of genes controling apoptosis
Definition
overproduction of BCL-2 in follicular lymphoma
Term
what is an example of recessive mutation of genes controling apoptosis
Definition
homozygous loss of p53 in most cancers
Term
what is the two hit hypothesis
Definition
two mutations are needed to cause retinoblastoma (an many other cancers)

applies to all recessive cancer genes
Term
what are the two reasons cancer can divide unlimitedly
Definition
telomerase is turned on

alternative lengthening of telomeres mechanism
Term
how does the alternative lengthening of telomeres mechanism work
Definition
recombination and amplification of dna at chromosome ends
Term
what is the normal activity over time at the telomere, what is a telomere made of
Definition
repeat on end of chromosome with TTAGGG telomeres that shorten as the cell divides (unless it has telomerase like in germ or stem cells)
evuntally it will get too short and will register as DNA damage and signal apoptosis
Term
why does a tumor need to do angiogenesis, what if it doesnt
Definition
blood can only diffuse 2mm so when a big tumor grows blood cannot get to the center

some neoplasms grow so fast the interior necrosis
Term
how do tissues protect against excessive angiogenesis
Definition
tissues have anti-angiogenesis factors and angiogenesis inhibitors to keep it in check
Term
what are the ways cancer increases angiogenesis
Definition
loss of angiogenic inhibitors
production of angiogenic initiators
Term
what are the inhibitors of angiogenesis cancer turns off
Definition
p53 mutation allows for angiogenesis to start
Term
what are the angiogenic initiators cancer turns on, how are they induced
Definition
VEGF: controlled by RAS, induced by hypoxia inducible factor (HIF-1)

FGF: stored in ECM, released as tumor cleaves ECM during invasion
Term
how does angiogenesis work in benignn tumors
Definition
it dosent
the pituitary grows until it pushes on stella turcia and squishes the vessels and then it spontaneously regresses due to the nutrient limitation
Term
what are the 4 things a cancer needs to overcome to metastasise
Definition
breech BM, interstitial CT, and vessel wall
evade host immune system
Term
what are 2 ways cancer tries to evade host immune system
Definition
form emboli with platelets so they hide in cell

travel as single cell and hope to not get caught
Term
what is the most common 2 places of cancer spread
Definition
liver and lungs
Term
what are the 2 least common places for cancer spread
Definition
skeletal muscle
Term
where does a cracinoma usually spread
Definition
lymph
Term
where does a sarcoma usually spread
Definition
hematogenous
Term
where does colon carcinoma usually spread
Definition
penetrates gut wall and spreads to peritoneal cavity
Term
where does lung cancer usually spread
Definition
pleural cavity
Term
where does ovarian cancer usually spread
Definition
peritoneum
Term
what are the 4 MOA to cancer malignancy
Definition
detachment of tumor cells from eachother
attachment of tumor cells to matrix components
degredation of ECM
migration of tumor cells
Term
3 ways tumor cells detach from eachother
Definition
inactivation of E-cadherin genes (in almost all epithelial cancers)

mutation of B-catenin genes

changes in cellular adhesion molecules (CAMs) gene expression
Term
how do tumor cells attach to matrix when traveling (2)
Definition
lamanin: cancer cells have receptors on all sides (unlike normal cells)

fibronectin: cancer cells dont have it so they can detach from ecm and reattach to it later
Term
how do tumor cells degrade ECM (4 steps)
Definition
tumor secretes proteases or stimulates fibroblasts to make...

MMP (matrix metalloproteases): digest protein

cathepsin D: peptodase

type IV collagenase
Term
how do tumor cells migrade (3)
Definition
clevage produces of some ECM components are chemotactic for tumor cells

tumor cell derived cytokines (autocrine motility factor)

growth factors IGF-1 and II
Term
what are the 3 most common cancers in men
Definition
prostate
lung and bronchus
colon and rectum
Term
what are the 3 most common cancers in women
Definition
breast
lung and bronchus
colon and rectum
Term
what are the 3 most deadly cancers in men
Definition
lung and bronchys
prostate
colon and retcum
Term
what are the 3 most deadly cancers in women
Definition
lung and bronchys
breast
colon and rectum
Term
where do most cancers come from
Definition
epithelium
Term
how can mortality of cancer be determined, give two examples
Definition
more preventable = more deadly

smoking: lung cancer
western diet (low fiber, high fat): colon and rectal cancer
Term
who is cancer more common in
Definition
elderly and men
Term
what is the common cause of cancer in the young
Definition
genetic mutation
Term
what is the most common cancer in japan
Definition
stomach
Term
what is the most common cancer in us
Definition
breast
Term
what is the most common cancer in africa
Definition
hepatocellular carcinoma
Term
what is the most common cancer in KY, why
Definition
lung and bronchial
number one smoking state
Term
where does hepatocellular carcinoma come from, what cancer does it cause
Definition
aspergillus in moldy nuts and grain releases alfatoxin causing carcinogens that progresses to liver cancer
Term
what is the most potent carcinogen
Definition
alfatoxin from aspergillus
Term
what is the most common origin for cancer under 4yo
Definition
neural or hematopoetic
Term
what is the most common origin for cancer over 4yo
Definition
soft tissue
Term
how can familial cancers be identified
Definition
in 2+ close relatives
multiple or bilateral tumors
Term
what are the six causes of acquired paraneoplasitc disorders
Definition
persistent regenerative cell replication

hyperplastic and dysplastic proliferation

chronic atrophic gastritis

chronic ulcertive colitis

leukoplakia of oral cavity, uvula, or penis

vilous adenomas of the colon
Term
two examples of persisent regenerative cells replication causing cancer
Definition
squamous cell carcinoma in long unhealed wounds

hepatocellular carcinoma in cirrhotic liver
Term
two examples of hyperplastic and dysplastic prolieration causing cancer
Definition
endometrial carcinoma from hyperplasia

bronchogenic carcinoma in dysplastic bronchial mucousa of smokers
Term
one example of chronic atrophic gastritis causing cancer
Definition
gastric carcinoma in pernicious anemia
Term
example of chronic ulcerative colitis causing cancer
Definition
colorectal carcinoma
Term
example of leukplakia of oral cavity, vulva, or penis causing cancer
Definition
squamous cell carcinoma
Term
example of vilous adenoma of the colon causing cancer
Definition
high risk of transformation to colorectal carcinoma
Term
explain the normal process of regulation og G1 to S stage of the cell cycle
Definition
cyclins are transcribed from DNA and complex with CDK phosphorlyating them

complexes phosphorlyate RB protein

RB protein release E2F transcription factor

E2F promotes proteins allowing cell to go from G1 (rest) to S (prep for division)

in M phase RB is dephosphorlyated

RB binds E2F transcription factor

cell division stops in G1
Term
what three oncogene dysruptions in the cyclin cell regulation cause cancer
Definition
cyclin D over expression

CDK4 over expression

CDK inhibitor down regulation
Term
what differnt combinations of cyclins and CDK are there (4)
Definition
cyclin D with CDK4 or CDK 6

cyclin E with CDK2

cyclin A with CDK
Term
what does cyclin D overexpression cause to happen, what three cancers have this
Definition
lots of CDK4 activation

breast, liver, lymphoma
Term
what does CDK4 over expression cause to happen, that three cancers have them
Definition
lots of RB phosphorlyation

sarcoma, melanoma, glioblastoma
Term
how are CDK inhibitors rendered ineffective by oncogenes (4)
Definition
down regulation
degredation
cytoplasmic mislocation
sequesteration
Term
what occurs in a RB mutation
Definition
RB cannot be dephosphorlyated so it cannt bind E2F
Term
what are the three types of RB mutations
Definition
familial retinoblastoma
sporadic retinoblastoma
oncogenic virus retinoblastoma
Term
familial retinoblastoma: inheritence, effets (2)
Definition
autosomal recessive but looks like dominant because it is only one random mutation away from dominant

retinoblastoma and WATCH OUT FOR osteosarcoma
Term
what occurs in sporadic retinoblastoma
Definition
both normal RB genes get a somatic mutation
Term
what occurs in oncogenic virus retinoblastoma, 3 example viruses
Definition
virus binds RB so it cannot bind E2F

(polyomavrus, adenovirus, HPV)
Term
explain how normal p53 works (2 prep steps, 3 cell effects)
Definition
DNA damage signals unbinding of p53 from MDM2

p53 activates transcription factors that turn on genes to...

1. activate CDK inhibitors stopping cyclin/CDK complexes from phosphorlyating RB protein pausing the cell cycle

2. activate DNA repair

3. activate apoptosis if it is not successful
Term
what does p53 do in a successful and unsuccessful DNA repair
Definition
success: p53 promotes transcription of MDM2 which degrates p53 (short half life)

not: p53 promotes transcription of apoptosis genes (like BAX)
Term
what are three ways to have a p53 problem
Definition
Li-fraumeni syndrome - inherited
inhibited by DNA viruses
acquired- two random mutations
Term
what occurs in li-fraumeni syndrome, what is the effect
Definition
inherit 1 p53 mutation in every cell
25x chance of malignancy by 50 yo
Term
how do viruses inhibit p53, 3 example viruses
Definition
proteins of virus encode oncogenes
(HPV, HBV, EBVg7)
Term
how does TGF-B regulate cell cycle
Definition
binds receptors 1-3 and sends signal to SMAD and stimulates CDK1 which stops transcription of cyclin E and A, stopping cell in G1
Term
when is TGF-b mutated, what part of the process is normally wrong
Definition
mutated in cell cancers

usually SMAD4 or type II receptor mutation
Term
explain how cell size is regulated
Definition
B-catenin senses cells are too far away and activates growth
B-catenin binds E-catenin making intracellular adhesions when cells are closing stopping B-catenin from activating cell growth
Term
what is the role of APC, how does it work
Definition
some B-catenin will be unable to pair with C-cadherin and may still go to the nuclei and say for the cell to grow

APC comes in and complexes with TcF transcription factor in quiescent cells forming destruction complexes and degrading excess B-catenin
Term
what occurs in a homozygous APC/B-catenin mutation
Definition
loss of APC activity stops degradation of B-catenin causing trancription of cell cycle proteins and cell growth
Term
what occurs in a heterozygous APC/B-catenin mutation
Definition
familial adenomaus polyposlsosis:
adenomatus polyps form on colon in teens and 20s
some will ahve malignant transofrmation
Term
how does MYC work
Definition
cell is induced to divide so MYC binds DNA causing transcription of growth genes (like CDK)

right after delivering the message they should stop being made
Term
what happens in a oncogene induced MYC mutation
Definition
amplification of a region that contains MYC
Term
what are the 4 oncogene induced MYC mutations
Definition
MYC over expression
N-MYC over expression
L-MYC over expression
burkitt lymphoma (B cell tumor)
Term
what cancers result from MYC over expression (3)
Definition
breast, colon, lung
Term
what cancer results from N-MYC over expression, what is a microscopic sign
Definition
neuroblastoma

karotype double minutes (little MYC chromosomes with repeats)
Term
what cancer results from L-MYC over expression, what is a microscopic sign
Definition
small call cancer in the lung

karotype double minutes (little MYC chromosomes with repeats)
Term
what is the cause of burkitt lymphoma
Definition
B cell tumor due to translocation of MYC from CH8 to CH14 next to heavy chain Ig genes increasing Ig production in WBC
Term
what should a chromosome 14 issue tell you
Definition
lymphoma
Term
how does ABL work
Definition
phosphorlyates things via tyrosine kinase, sends signals to nucleus, promotes apoptosis when DNA is damaged
Term
explain how oncogenes cause ABL translocation
Definition
oncogene induces translocation of ABL from CH9 long arm to CH22. ABL is now with BCR making phildelphia chromosome. CH9 becomes abnormally long and CH22 short.
Term
what does a ABL translocation cause to happen within the cell
Definition
TK activates RAS which cannot localize to the nucleus and apoptosis stops
Term
what is a phildalphia chromosome diagnostic for
Definition
chronic myeloid leukemia
Term
what does RAS do
Definition
GF binds RAS receptor which signals cell proliferation via MAP kinase mediated transcription of cell cycle proteins

inactivated RAS is bound to GDP after ONE signal is sent
Term
what is the most common oncogene mutation, what happens
Definition
RAS mutation

GTPase activity is broken and RAS is always activated causing continous transcription of cell cycle proteins
Term
what are two categories of issues an oncogene can cause with growth factor receptors
Definition
mutant receptor proteins deliver continous mitogenic signals to cells

over expression of growth factor receptor
Term
what occurs in a mitogenic EGF receptor mutation
Definition
it is continously activated (despite absence of EGF or TGFa and more cell division occurs allowing more chance for mutations
Term
what occurs in oncogenic over expression or ERBB1 EGF, where does this happen
Definition
increased activation
squamous cell carcinoma
Term
what occurs in HER3 (ERBB2) oncogenic over expression
Definition
increased activation causes gene to be expressed over and over and so when transcription is turned on HER2 builds up on surface of cellls causing breast cancer
Term
how is apoptosis regulated and activated
Definition
BCL-2 binds BAX so cytochrome C isnt activated

BCL-2 lets go of BAX which binds BAD which activates cytochrome C which binds APAF-1 which begins capsase cascade
Term
what are three types of apoptosis mutations
Definition
BCL-2 over expression
follicular lymphoma
APAF-1 mutation
Term
what occurs in BCL-2 over expression
Definition
too much BAX is stopped so apoptosis cannot occur
Term
what occurs in follicular lymphoma
Definition
BCL-2 translocates from Ch12 to CH14 by Ig heavy cjain gene causing excessive (not rapid) proliferation
Term
what occurs in a APAF-1 mutation
Definition
loss of functional gene in some melanomas
Term
how does UV ratiation cause neoplasm
Definition
causes pyrimidne dimers in DNA mutating protoncogenes and tumor supressor genes causing skin cancer
Term
what causes ionizing radiation
Definition
X, Y, a, B rays, protins, neutrons
Term
how does ionizating radiation cause neoplasm
Definition
causes ss and ds breaks of cells, especially those in G2
Term
what is an example of RNA oncogenic virus that causes neoplasm, what kind of neoplasm
Definition
human T cell leukemia virus (HTLV-1) targets CD4 causing leukemia
Term
what are three DNA oncogenic visues and what neoplasm do they cause
Definition
hepatitis B: hepatocellular carcinoma
EBV: burkitt (B cell) lymphoma
HPV: benign squamous cell papilloma
Term
what types of HPV cause cervical cancer
Definition
16 and 18
Term
what kind of cancers are HPV very commonly involved in
Definition
75% of squamous cell carcinoma and 100% of preneoplastic disorders (dysplasia)
Term
what is HHV8
Definition
kaposki sarcoma associated herpes virus
Term
what two parts of HPV cause problems
Definition
viral proteins E6 and E7
Term
what does HPV viral protein E6 do
Definition
inhibit p53 stopping apoptosis
Term
what does HPV viral protein C7 do (3)
Definition
inhibits p53 stopping apoptosis

inhibits p21 which now can no longer inhibit cyclin D / CDK4 complex so now it can run free and cause growth

inhibits RB-E2F complex so it can cause transcription and growth
Term
what neoplasms does helobacter pylori cause
Definition
gastric carcinoma and gastric lymphoma (aka marginal lymphoma or maltoma)
Term
what is evidence that host immune defenses have a role in tumor frmation
Definition
increased risk of cancer and autoimmune disease
Term
what are the two types of tumor antigens, where are they located
Definition
on cell surface MCH-1 to be recognized by CD8

tumor specific antigens: only on tumor cells

tumor associated antigens: on tumor cell and some normal cells
Term
where are tumor specific antigens appearing (5)
Definition
oncoprotein (RAS), over expressed proteins (HER-2), oncogenic virus antigens, oncofetal proteins (CEA), a-feroprotein
Term
what are the types of tumor associated antigens
Definition
tissue specific and differentiation specific
Term
what is an example of a tumor associated antigen, what can it be used for
Definition
prostate specific antigen

not good for prostate cancer because it shows cancer, inflammation, enlargement, ejaculation, etc
Term
anything that decreases immunity....
Definition
increases risk for cancer
Term
list 4 cancer immunosurvelence mechanisms
Definition
subclones with antigens recognized by immune system are eliminated

tumor may have abnormal HLA and get destoried

tumor may not have co-stimulatory molecules for sensitization to T cells

immune supression by carcinogen or expression of FAS B tumor stimulates apoptosis of T cells
Term
what are the 4 clinical features of a neoplasm
Definition
impinge on adjacent structures

hormone production

ulceration

cancer cachexia
Term
what are two examples of a neoplasm impinging on adjacent structures
Definition
pituitary adenoma: compresses and destories gland (hypopitutiarism)

carcinoma of the bile duct: fatal biliary tract obstruction
Term
what are two examples of a neoplasm secreting hormones
Definition
adenoma in islets causes hyperinsulinism

carcinoma of adrenal cortex causes hyperaldosteronism
Term
what are 4 complications of neoplasm ulcer
Definition
bleeding
predisposition to infection
gastric ulcer can cause Fe deficient anemia
intrussuception: tumor protrudes into lumen and causes telescoping leading to infarction
Term
what are 5 signs of cancer cachexia
Definition
cancer wasting syndrome: loss of body fat and mass, weakness, anorexia, anemia

with increased metastasis comes increased cachexia
Term
what are 4 persumed causes of cancer cachexia
Definition
increased calories expended and basal metabolic rate

reduced food intake due to abnormal appetite control

protein mobilizing or lipolytic molecules released caused by tumor or host cytokines and proteolysis factor release

TNF release inhibiting appetite and lipoprotein lipase
Term
what are 5 examples of paraneoplastic syndromes
Definition
cushings syndrome
SIADG
hypercalcemia
venous thrombus
non-bacterial thrombotic endocarditis
Term
define paraneoplastic syndrome
Definition
cannot be explained by tumor tiself, its origin, or secretions
Term
what are 3 concerns with paraneoplastic syndrome
Definition
early sign of neoplasm
lethal side effects
mimic metastastic pattern
Term
what are three neoplasms that are associated with cushings synfrom and what do they secete
Definition
small cell carcinoma of lung: insulin
pancreatic carcinoma: ACTH
neural tumor
Term
what are two neoplasms that are associated with SAIDH and what do they release
Definition
small cell carcinoma of the lung: ADH, ANP

intracranial neopasm
Term
what neoplasm is hypercalcemia associated with, what does it release
Definition
small cell carcinoma of the lungs: PTH, TNFa, TNF, IL-1
Term
what two neoplasms are associated with brnous thrombosis, what do they produce, what effect does this have
Definition
pancreatic carcinoma
bronchogenic carcinoma

make mucins that cause clotting
Term
what neoplasm is non-bacterial thrombotic endocarditis associated with, what does it secrete, what is the effect
Definition
found in advanced cancer

secretes tissue factors that cause hypercoagulation
Term
what is the purpose of staging and grading
Definition
quantify agressiveness and current spread
Term
what is the purpose of grading a tumor
Definition
tells agressiveness.
differes per type of carcinoma
tells how well differentiated
Term
what are the levels of tumor grading, what do they mea
Definition
1: typical tissue - well differentiated
2: nothing like the neighboring tissue
Term
what are the two ways to stage cancer
Definition
TNM and american joint comission
Term
what does TNM stand for
Definition
primary TUMOR
regional NODE involvement
METASTIASIS
Term
what are the 5 T rankings, what do they mean
Definition
Tis: confined to epithelium (in situ)
T1: small
T2: more invasion at primary site (medium)
T3: large - invasion beyone primary site margin
T4: very large - in adjacent tissues
Term
what are the 4 N rankings, what do they mean
Definition
N0: not spread to adjacent nodes
N1: spread to regional nodes
N2: spread to many regional nodes
N3: spread to distand nodes
Term
what are the 2 M rankings, what do they mean
Definition
M0: no metastasis
M1: metastasis
Term
what TNM is stage 0
Definition
Tis N0M0
Term
what TNM is stage 1
Definition
T1 N0M0
Term
what TNM is stage 2
Definition
T3 N0M0
Term
what TNM is stage 3
Definition
any T, N > 0, M0
Term
what TNM is stage 4
Definition
any T, any N, M1
Term
what are the three categories of testing for tumors
Definition
obtaining sample
immunohistochemistry
serum tumor markers
ancillary tests
Term
what are 4 ways to obtain a tumor sample
Definition
excision
biopsy
aspiration
smear (PAP)
Term
what is the purpose of tumor immunohistochemistry
Definition
determine tissue of origin of metastic or poor differentiated tumor
Term
how does immunohistochemistry work
Definition
monoclonal antibody markers are identified
Term
what are 4 examples of monoclonial antibody markers that are identified with immunohistochemistry and their associated cancers
Definition
thyrobluboin - thyroid cancer
S100 - melanoma or neural
CD markers - lymphoma/leukemia
estrogen - breast cancer
Term
what are the uses of serum tumor markers
Definition
tumor specific or associated markers that screen, monitor Tx, or detect recourrance of tumors
Term
what are three examples of serum tumor specific markers and their associated cancers
Definition
a-fetoprotein (AFP): hepatoma, testicular germ cell tumor
B-hCG: trophoblastic tumor, carcinoma
prostatic specific antigen: prostate cancer
Term
what are 4 ancillary tests for tumors, what two are used for prognosis
Definition
flow cytometry: prognosis
PCR/dnA probes
karyotyping: prognosis
flourescent in situ hybridization (FISH)
Term
what is a proband
Definition
person you are studying in a inheritence chart
Term
whem you have anemia in an adult you should think of...? why?
Definition
GI problem because Fe deficiency in the USA is very uncommon without some GI condition
Term
what is a guaiac test
Definition
fecal occult blood screen looks for RBC exodgenous peroxidase (turns blue)
Term
what does hematochezia mean
Definition
visible blood in stool, distal GI bleed
Term
what does melena mean
Definition
tarry black stool from blood exposed to digestive enzymes
stomach or upper GI bleed
Term
what causes a false positive guaiac test
Definition
rare meat
crvicterous veggies
horseradish
myoglobin
Term
what causes false negative guaiac test
Definition
ascorbic acid (reducers)
Term
what is the problem in LeFraumini syndrome
Definition
p53 mutation
Term
sporatic colon cancer: when does it appear, now many areas affected, how do you get it, where does it go
Definition
shows in older age
1 affected spot
little family hx (20%) its spontanous
majority on left/distal colon
Term
familial adenotamous polyposus: cause, when does it appear, how many areas affected, how do you get it, where does it go
Definition
APC mutation allows B-catenin into cell to allow division
appears in 20-30s
thousands of polyps
germline mutation
majority on left/distal colon
Term
hereditary non-polypupus cancer syndrome: when does it show up, how many areas effected, how do you get it, where does it go
Definition
shows in 40s
several polyps
family history of colon cancer (1 inherited mutation increases chances of more)
appears in right/proximal colon
Term
what cancers is HMPCC associated with
Definition
endomterial and ovarian
Term
what causes HMPCC
Definition
microsatelite instability in APC gene

repetative microsatelites are subject to mismatch and when DNA replicates it slips and messes up so DNA mis match repair fixes it. but the repair gene is broken so it allows for amplication of the microsatelites

if this occurs in a coding gene (like APC) it allows for bad proteins. bad APC allows B-catenin to keep allowing cell replication
Term
how is HMPCC identified in the lab
Definition
immunohistochemistry

antibody used against genes. if they bind there gene is there and working.

varability in length of microsatelites in ANY (not just the tumor) tissue can cause mis match repair issue
Term
what does a TP53 mutation cause to happen
Definition
prevents apoptosis in all cancers
Term
how often is a RAS mutation seen
Definition
30% of all tumors
Term
explains what happens in chronic myeloid leukemia
Definition
ABL normall detects DNA damage and uses TK to phosphorlyate to cause apotosis

ABL is translocated from Ch9 to Ch22 where it fuses with BCR and activates RAS causing cell cycle protein trancription and is prevented from going to nucleucs to start apoptosis
Term
what gene mutations cause growth promotion (5)
Definition
HER2
RAS
ABL
MYC
CD/CDK4
Term
what gene mutations cause loss of tumor supression (3)
Definition
RB
TGF-B
APC
Term
what gene mutations cause stop of apoptosis (3)
Definition
TP53
BCL-2
APAF-1
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