Chapter 7 Flashcards
What are the two basic components of all tumors?
- tumor parenchyma ( neoplastic cells)
2. reactive stroma ( connective tissue, blood vessels, variable cells of immune and adaptive response
_______ is chracterized by unregulated proliferation that becomes autonomous. “New growth”
Neoplasia
What does it mean for neoplasia to be clonal?
It arises froma. SINGLE CEll. (monoclonal characteristic)
_______ is characterized by Abnormal growth of cells or edema that leads to swelling of tissue
Tumor
__________ is a benign mass composed of mature cells that are native to the tissue of origin but have abnormal tissue organization
Hemartoma
A sarcoma is a malignant tumor arising from ?
solid mesenchymal tissue
ex. fibrsarcoma, chondrosarcoma
A leukemias/lymphomas is a malignant tumor arising from ?
from blood forming cells ; white blood cells
A carcinoma is a malignant tumor arising from ?
epithelial lineage
any of the three germ layers
Papilloma and adenomas are examples of what type of neoplasms?
Benign
A neoplasm that has mature/immature cells from more than one germ cell layer orginates from ?
Totipotent germ cells
This is a TERATOMA
Which neoplasm is extremely RARE im children.
Carcinomas (of epithelial cells)
____is a visible projection above a mucosal surface and projects into gastric or colonic lumen
Polyp
called ADENOMATOUS polyp if the polyp has glandular tissue
Which malignant neoplasms have inappropriate benign terminology?
lymphoma
melanoma
mesothelioma
seminoma
Which of the folllowing will resemble their corresponding normal parenchymal tissue the most?
A. melanoma B. adenoma C. carcinoma D. mesothelioma E. teratoma
B.
All others are malignant
ANAPLASIA (lack of differentiation is a hallmark of malignancy
Can you have a benign proliferation of lymphocytes?
NO
that is only with malignancy!
Dysplasia is a term used only with ____________cells
epithelial
______________is massive amounts of mucus in the peritoneum
pseudomyxoma peritonei
pg 273
it is a result of SEEDINg of malignant tumors
What is a sentinel node and its significance?
- first node in regional lymphatic basin that receives lymph flow from the primary tumor
- BIOPSy of this used for detection FOR PRESENCE OR ABSENCE of metastatic lesions
What is the only absolute criteria for malignancy?
Metastasis
Carcinomas typically spread via?
lymphatics
Sarcomas usually spread via?
Hematogenous spread
Which cancers have a propensity for invasion of veins?
- renal cell carcinoma
2. hepatocellular carcinoma
Cancers arising in close proximity to verterbral column embolize through ?
paravertebral plexus
ex. thyroid and prostate carcinomas
HPV diagnosis predisposes someone to which carcinoma?
- Cervical carcinoma
2. head and neck carcinomas
What are (4) precursor lesions that are associated with high risk of cancer?
- metaplasia
- non inflammatory hyperplasia
- leukoplakia
- benign neoplasms
Mutations that cause overexpression of which two growth factors ___________ can precipitate development of an Astrocytoma
PDGFB growth factor
TGF B
What is the associated tumor that results from overexpression of the PDGFB oncogene?
Astrocytoma
What is the associated tumor that results from AMPLIFICATION of the HER2/neu (c-erbB2) oncogene?
Breast cancer
What type of oncogene is HER2/neu (c-erbB2)?
Growth factor receptor
What is the associated tumor that results from GAIN of function of the ALK oncogene?
Neuroblastoma or Adenocarcinoma of lung
Translocations of the ABL proto-oncogene are associated with?
chronic myelogenous leukemia
Fusion of ALK with EML4
results in what type of malignancy?
lung adenocarcinoma
MUTATION of ERBB1 results in what carcinoma?
Adenocarcinoma of the lung
Gain of functions in the BRAF oncogene result in which cancers (3)
- melanoma
- colon carcinoma
- hairy cell leukemia
Chronic myelogenous leukemia can be treated using which of the following?
A. BCR- ABL antagonist
B. BRAF inhibitor
C. AKL inhibitor
D. HER2 inhibitor
A. the fusion of BCR -ABL as a result of ABL translocation is associated with CHronic myelogenous leukemia
Which of the following relates to the principal of oncogene addiction?
A. tumor cells are not dependent on activity of oncogenes
B. CML responding to ABL inhibitor
C. ALK inhibitor for treatment of breast carcinoma
D. ERBB1 inhibitor for leukemia
C. The term “oncogene addiction” describes a tumor dependent on a single oncogenic pathway or protein for its sustained proliferation and/or survival.
CML depends on ABL oncogene
Pt presents with headache fatigue. Pt is not hypoxic and otherwise appears normal. CBC shows a high hematocrit, elevated white blood cells and red blood cells. To further explain this persons condition what should test for next?
JAK2 mutation
JAK 2 contributes to myeloproliferative disorders which means abnormal proliferation of RBCS
pg 288
A TRANSLOCATION of which oncogene results in overexpression and ultimately Burkitt Lymphoma?
MYC
What is the associated tumor that results from AMPLIFICATION of the N-MYC oncogene?
Neuroblastoma
Translocation of ABL from chromosome _____ to ______ is related to oncogenesis of CML
9; 22
pg 287
Translocation of MYC from chromosome _____ to ______ is related to oncogenesis of Burkitt lymphoma
8; 14
pg 287
Mutations in which tumor suppressor genes. (2) allows for G1/S phase progression?
RB / p53
Gain of function of Cyclin D results in ?
uncontrolled progression through G1/S
Which of the following does NOT contribute to uncontrolled growth of cancer?
A. loss of function of TP53 B. gain of function of Cyclin D C. Loss of function of RB D. loss of function of CDK4 E. amplification of MYC
D.
it should be a GAIN of function of CDK4
Normal function of CDKS is to promote progression of cells to cell cycle
What is the normal state of RB and its normal function?
RB is normally hyperphosphorylated
It blocks progression into cell cycle
Which 4 mechanisms contribute to antiproliferative effect of RB?
- loss of function of RB
- gene amplification of CDK4
- loss of cyclin dependent kinase inhibitors
- viral oncoproteins that bind RB (HPV
With uncontrolled cell cycle progression you would see which of the following?
- increase in p16
- decreased Cyclin D
- increase E2F
- decrease viral oncoproteins
- A mutation in Rb results in constitutively free E2F leading to uncontrolled cell cycle progression
What is the normal function of p53 and what is it bound to in quiescent states?
P53 induces cell cycle arrest/ death under
bound too MDM2
A person with Li fraumeni Syndrome will demonstrate loss of function mutation of ?
TP53
A person with Li fraumeni Syndrome will demonstrate germline loss of function mutation of ?
TP53
What two suppressor genes are inactivated by viral oncoproteins?
RB (HPV E7) and p53 (HPV E6)
A 40-year-old woman presents to her primary care physician with rectal bleeding. On rectal exam, her PCP can feel discrete polyps. Pale red blood coats his finger after the exam. She is adopted and knows no family history of colon cancer. Which of the following would you see with further testing?
A. increase E2F activity B. increased B catenin activity C. loss of function of p53 D. decreased Wnt signaling E. increase of HIFs
B. this describes colonic polyps which is due to decreased APC sequestering of B catenin ( increased Wnt signaling)
so B catenin activates transcription of growth factors
A 23-year-old man presents with tumor that develops from the Schwann cells in the peripheral nervous system (schwanomma). Which of the following is contributing to his condition?
A. decrease in GTPase activity
B. decrease in cytoskeletal protein
C. decrease in DNA repair factors
D. decrease in cell adhesion molecule
Pt has a schwanomma. Which is related to loss of function of NF2 ( this encodes a cyctoskeletal protein merlin OR neuro fibrin 2
Pt presents with Gorlin syndrome. The increased hedgehog signaling increases risk for this pt to develop which of the following sporadic carcinoma?
A. schwanomma B. neuroblastoma C. retinoblastoma D. basal cell carinoma E. colonic carcinoma
D. Gorlin syndrome is a result of loss of function of PTCH (patched protein)
Table 7-7
(sporadic cancers)
A. NF2
B. WT1
C. RB
E. APC
Lack of inhibition of HIFs can cause….
- familial retinblastoma syndrome
- Li Fraumeni Syndrome
- Von Hippel Lindau Syndrome
- Gorlin Syndrome
- loss of function of VHL
NOT
- RB
- TP53
- PTCH
germline loss of function of __________ can result in nonpolyposis colon carcinoma.
MSH ( function is to repair DNA mismatch
Biallelic loss of function mutation in VHL are common in which sporadic carcinoma?
REnal cell carcinoma
Nivolumab is an anti-checkpoint monoclonal antibody that binds to _________on T cells.
PD1
Avelulab is an immunostimulant that works by targeting the ________ to allow T cell killing of tumor
PD-L1
Which drug is associated with CTLA-4 targeting to treat cancer?
ipilimumab
jhas serious side effects compared to drugs targeting PD1
Which of the following should be targeted to help treat someone with Psoriasis?
A. CTLA4
B. PDE4
C. PD-1
D. CAMP
B.
PDE4 decreases CAMP
CAMP is known to promote antiinflammatry mediators
Which of the following should be targeted to help treat someone with Psoriasis (aberrant inflammation of the skin)?
A. CTLA4
B. PDE4
C. PD-1
D. CAMP
B.
PDE4 degrades CAMP
CAMP is known to promote antinflammatory mediators (you want more CAMP to treat psoriasis)
The Warburg effect states that cancers produce energy via a high rate of glycolysis followed by _________
lactic acid fermentation
Which apoptotic pathway is most often disabled in cancer?
intrinsic (mitochondrial)
List some ways cancer avoids apooptosis?
- loss of p53 expression
- overexpression of BCL2 (antiapoptotic )
- increased inhibitors of apoptosis (IAP)
fig 7-33
Matrix metalloproteases and cathepsins are relased from tumor cells and stromal cells to promote degradation of??
Basement membrane to allow for metastasis
Which 2 genes promote EMT (epithelial -mesenchymal transitions) to promote metastasis?
TWIST and SNAIL
The epithelial–mesenchymal transition (EMT) is a process by which epithelial cells lose their cell polarity and cell-cell adhesion, and gain migratory and invasive properties
Which gene products (3) induce genomic instability and can result in development of lymphoid neoplasms?
RAG1, RAG2, AID
Hereditary nonpolyposis colon cancer is characterized by …
A. mismatch repair defects
B. defect in nucleotide excision repair
C. defect in homologous recombination
A.
NOt B. related to xeroderma pigmentosa
Not C. related to Bloom syndrome or ataxia telangiectasia
What is the result of deletions of miRs ?
mIRs, normally silence mRNA translation
if deleted , will contribute to carcinogenesis because it has tumor suppressor properties
What molecular step must occur to transition from an adenoma to A carcinoma ?
HOMOZYGOUS LOSS OF cancer suppressor genes
*** cancers arise from accumulation of multiple mutations
What is the role of long noncoding RNAs?
Normally they restrict RNA polymerase accessing genes
If abnormal could lead to carcinogenesiis
A 47-year-old man presents to the emergency room with 2 months of fevers, cough, and night sweats. He also reports having hemoptysis. He recently tested negative for tuberculosis. Lab results showed positive culture for Aspergillus.
What chemical carcinogen is associated with this patients presentation?
Aflatoxin- is produced by aspergillus a fungus/strain of mold
pg 323
ASpergillus
What is an example of direct acting carcinogen
alkylating agents
What is an example of indirect acting carcinogen?
aflatoxin, benozo -pyrene
A 42-year-old fair-skinned woman is concerned about a mole on her cheek. She has no significant past medical history, but reveals that she regularly goes to tanning salons and beaches. She admits that she occasionally forgets to apply sunscreen and does not re-apply when she is outside all day.
What do you expect to be true of her condition?
A. presence of pyrimidine dimers in DNA
B. increased DNA strand breaks
C. increased chromotrypsis
A. carcinogenicity of UV light is due to formation of pyrimidine dimers in DNA
Place the following in order of decreasing vulnerability to radiation induced cancer
A. breast , lungs, salivary galnd
B. thyroid cancer
C. myeloid leukemia
C> B> A
Myeloid leukemia is most frequent result of ionizing radiation induced cancer
Which wavelength of UV is most responsible for formation of cutaneous cancer?
UVB
NOt UVA or UVC
What protein is that contributes to transforming activity of viral HTVL-1?
Tax protein
- increases cyclin D
- it interferes with DNA repair
- increases genomic stability … etc
A 55-year-old woman presents to the emergency room with a 5-month history of worsening back pain. She recently immigrated from Japan and has a history of sexually transmitted diseases, each successfully treated. Imaging of the spine is normal. Serologic testing is positive for a retrovirus.
Pt has which of the following?
A. EBV
B. HTLV1
C. HPV
D. Merkel cell polyomavirus
B. HTLV1
- is transmitted through sexual activity, blood , breastfeeding
- high occurence in JAPAN, S. aMerica, carribena
- RETROVIRUS
A 38-year-old female presents to the clinic with a history of soft, raised flesh-colored warts on the labia majora. She is sexually active with multiple partners and uses condoms infrequently. What is this person at risk to develop?
A. lung carcinoma
B. adult t cell leukemia
C. neck and head tumor
D. B cell lymphoma
Pt presents with HPV
HPV increases risk for cervical cancer AND head and neck tumors
An elderly Chinese male comes into your office for repeated episodes of nose bleeds. On exam, you notice swelling of the nasal mucosa and biopsy confirms a tumor. Which of the following is most associated with this condition?
- Human Herpes Virus-8
- Epstein Barr Virus
- H. pylori
- .Alcohol Intake
- EBV is rrelated to increased risk of NASOPHARYNGEAL carcinoma
- prevalent in CHINA , africa
- causes Nasal tumor
A 35-year-old man presents to his primary care physician for routine check-up. During this visit, he states he has been feeling excessively fatigued with weight loss, lack of energy, and abdominal discomfort. He has a history of alcohol abuse as well as acute hepatitis. On PE, he has mild tenderness to palpation. Laboratory evaluation shows elevated liver enzymes and confirmed presence of DNA virus.
Which of the following is also true regarding this patient?
A. elevated Hbx protein B. elevated tax protein C. elevated E6 protein D. Elevated E7 protein E. elevated Cag A
A. this pt is likely to have developed hepatocellular carcinoma associated with HBV
-HBV causes chronic inflammation and liver injury
HBx protein is impt for carcinogenesis of HBV
NOT HCV because HCV is RNA virus
A 78-year-old man presents to his primary care physician for abdominal pain. His abdominal pain is in the epigastrium and has been persistent. He has unintentionally lost 10 pounds over the course of 3 weeks. He has a past medical history of H. pylori infection.
Which of the following is most likely also true regarding this patient?
A. elevated Hbx protein B. elevated tax protein C. elevated E6 protein D. Elevated E7 protein E. elevated Cag A
E. Cag A associated with gastric adenocarcinoma which can be a result of past H. pylor infection
Which immune mediator contributes to cancer cachexia?
TNF alpha
What laboratory method should be used to detect antigens in a leukemia?
Flow cytometry
used to identify antigens in LIQUID tumors f BLOOD forming tissue
What laboratory method should be used to determine the origin of a metastatic tumor?
Immunohistochemistry
What laboratory method should be used to detect and characterize RARE solid tumor cells?
assessment of Circulating Tumor cells
Which 3 tumor markers are used to detect for reCurrence of tumor after excision? (lack specificity and senstivity)
PSA, CEA , AFP
Detection of tumor markers RAS , TP53 and APC is related to which tumor?
Colon cancer
Detection of RAS and TP53 in sputum and serum relates to what cancer?
Lung cancer
Detection of RAS and TP53 in sputum and serum relates to what cancer?
Lung cancer
Detection of HcG relates to what cancer?
trophoblastic tumors
Detection of which of the following relates to ovarian cancer?
CA 125
CA19-9
CA 15-3
CA 125
Detection of which of the following relates to ovarian cancer?
CA 125
CA19-9
CA 15-3
CA 125
CA 19-9 colon/ pancreatic cancer
CA 15-3 breast cancer
A 65-year-old man with a 40 pack-year smoking history presents to his primary care physician for fatigue and cough. He reports that his symptoms began approximately 1 year ago and has progressively worsened. Physical examination is notable for finger clubbing. Which of the following is most likely an associated clinical symptom?
- myasthenia
- DIC
- hypertrophic osteoarthropathy
- hypercalcemia
- dermatomyosistis
- hypertrophic osteoarthropathy is a paraneoplastic syndrom associated with bronchogenic carcinoma (lung cancer)
table 7-11
Acanthosis Nigricans can present as a paraneoplastic syndrome associated with ___________
Gastric carcinoma
Myasthenia is a paraneoplastic syndrome associated with __________
Thymic neoplasms
or n
bronchogenic carcinoma
Which paraneoplastic syndrome is associated with Acute promyelocytic leukemia?
DIC
Which cells undergo metaplasia to become malignant?
precursor stem cells, NOT adult differentiated cells
The growth and spread of a tumor is dependent on ?
stroma
- made of CT, blood vessels, and variable amounts of other cells of the immune system
How would you name benign epithelial neoplasms that produce papillary patters that protrude into cystic spaces?
papillary cystenadenoma
What morphological changes are seen in tumors?
pleomorphism
- abnormal nucleus (1:1 ratio of nucleus to cytoplasm, irregular shape, hyperchromatic)
- many cells in mitosis (may be seen in normal rapidly dividing tissues)
- atypical, bizarre mitotic figures that can have tri-, quad-, or multipolar spindles
- loss of polarity
- ischemic necrosis
What does the likelihood of whether or not a cancer will metastasize correlate with?
- lack of differentation
- aggressive local invasion
- rapid growth
- large size
Most common way for carcinomas to spread initially
via lymphatics
Which tumor suppressor gene is associated with increased risk of osteosarcoma ?
RB
with both osteosarcoma and retinoblastoma
in order to invade, tumors downregulate expression of which protein to allow deattachment from primary tumor?
E CADHERIN
*** allows for deattachment of tumor cells from primaru tumor
pg 293 and pathoma
Explain the steps of InVasion of tumor ? (4)
- dissociation of cancer cells from one another (E cadhering decrease)
- degrade Basement membrane (proteolytic enzymes)
- attach cells to ECM proteins (ex. laminin)
- locomotion into BM that was degraded
Is dysplasia reversible or irreversible?
REVERSIBLE : if it does not involve full thickneess of epithelium
irreversible : when it becomes a neoplasm
What are the most prevalent cancers in MEN in DEVELOPING nations?
lung, stomach, liver
What are the most prevalent cancers in WOMEN in DEVELOPING nations?
lung, cervix , breast
Overexpression of BCL2 results in what type of cancer?
Follicular lymphoma (translocation 14:18)
What is the role of MYC in the limitless replicative potential of cancer?
MYC upregulates TELOMERASE
Loss of expression of ___________ causes increased invasiveness, loss of cohesiveness of tumor
E cadherin
What would be the function of VEGF inhibitors?
SLOW growth of cancer
Cancer needs blood supply (angiogenesis) to grow
IN a person with previous H. pylori, what would eventually progress into gastric adenocarcinoma?
CHRONIC gastritis
the development of gastric cancer due to H pylori has to due with INCREASED cell proliferation due due CHRONIC INFLAMMATION
A MALToma (which is a proliferation of B and T cell) can acquire constituitive activation of _______________ which allows it to continue to grow
NF kB
maltoma is a result of H.pylori
Local excision of _________ has 100 % cure rate
in situ carcinoma
doesnt invade and is limited to epithelium
Loss of function mutations in GAP ( GTPase activating proteins) results in similar effect as Gain of function of _______
RAS
- upregulates MAPK and PI3K / AKT
contributes to colon, lung and pancreatic cancer
germline mutations of p16 has increased risk for ________
familial melanomas
p16 (cell cycle inhibition)
p16 inhibits cDKS, but if mua
Loss of the second copy in (Rb) leads to the occurrence of__________
retinoblastoma in CHILDREN
List the 2 growth inhibitors
TGFB and p53
these stimulate the CDK inhibitors
pg 293 fig 7-29
List the 2 growth factors?
EGF, PDGF
these activate the cyclin D to proceed with cell cycle
Explain how a loss of NF1 gene relates to RAS activity?
NF1 codes for a GAP genes (GTPas activating protein) that allows for increase in RAS activity.
this leads to FAMILAL NEUROFIBROMATOSIS
Mutant NF1 allele can result in ?
malignant peripheral nerve tumor
What germline gene mutation is associated with schwannoma of acoustic nerve, decreased merlin protein and cells lacking stable cell to cell junction?
NF2
What two factors help determine where a circulating primary tumor will metastasize?
- tumor cells with certain adhesion molecules matching a certain organ
- chemokines
Expression of _______ enhances spread of cancer to lymph nodes and other metastatic site.
CD44
Immunocompromised individuals like those with HIV and AIDs or XLP (x linked lymphoproliferative syndrome) are susceptible to what cancer __________?
B cell lymphoma
pg 313
IMMUNOCOMPRIMISED ppl are susceptible to viral induced cancers
Which tumor supressor gene inhibits invasion and metastasis of cancer?
CDH1 that encode E cadherin
E cadhering maintains cell to cell adhesion
