Path Flashcards
Lack of differentiation is defined as
Anaplasia
Dysplasia is
preinvasive - lesion is WITHIN epithelia
HAS NOT penetrated BM
Carcinoma in situ
Dysplastic changes are marked and involve the entire thickness of the epithelium
Incidence of cancers in men
1) Prostate
2) Lung
3) Colon
Incidence of cancer in women
1) Breast
2) lung
3) colon
cancers by death for men and women
men
1) Lung 2) Prostate 3) colon
women
1) lung 2) breast 3) colon
% of cancers that are heritable
5-10%
Inherited cancers
- brca 1 and 2 mutations
NF
-MEN
FAP
DNA repair syndromes
Lynch syndrome
Xeroderma pigmentosum
stomach cancer incidence higher in
Skin cancer incidence higher in
prostate cancer incidence
Japan
Australia
african american
EBV can cause
burkitts
B cell lymphomas in immunosuppressed patients
nasopharyngeal carcinomas
H. pylori can cause
gastric adenocarcinomas
MALT gastric lymphoma
Characteristics of cancer
uncontrolled proliferation
loss of differentiation
invasion
metastasis
Self sufficiency in growth - Ret Ras Abl Myc Cyclin D1
RET: GDNF receptor –> MEN 2 often germline
RAS: active forms binds GTP - inactivated by GTPases- lung cancer
ABL: bCR-abL9/22- CML AML
MYC: amplified or translocation - N-myc: neuroblast L-myc: SCLC - Burkitt’s IgH/Myc
CYCLIND: Phophorylate Rb G1-S work with CDK4 and 6 IgH/CyclinD - Mantle cell lymphoma
IgH- Myc
IgH-CyclinD1
IgH - Bcl2
Burkitt’s 8/14 translocaton
Mantle cell lymphoma
B cell follicular
Insensitivity to growth inhibitory signals - TSG! Rb p16 cdk Inhib APC p53 others: Pten wT1 - Wilm's
Rb: Retinoblastoma - 2 mutations needed
p16: specific to CDK4 can have germline mutations and O/E!! in HPV
APC: wnt signaling Beta catenin translocation - FAP
Critical cell cycle regulators
CDK4, Cyclin D, Rb, P16
DNA repair genes p53 NER genes MLH MSH genes homologous recombination
p53: acts on p21, bound to mdm2, activates Bax Li Fraumeni
HPV e6 e7
MMR genes –> microsatellite instability - Lynch syndrome
HNPCC
NER genes –> xeroderma pigmentosum
HRR: Brca1 and 2
E2 genes in HPV normally
E6 binds…
E7 binds
suppress E6 and E7
p53 - degrades p53 AND Bax, activates telomerase
Rb: displaces E2F allow cell proliferation
Evading apoptosis
Bcl2
Follicular B cell lymphomas O/E bcl2
Limitless replicative potential
reactivation of telomerase
present in >90 % of cancers
Sustained angiogenesis
Bevacizumab - anti-VEGF monoclonal Ab
Locomotion of metastatic cells
hepatocyte growth factor scatter factor
Tumor antigen recognition
1) products of mutated genes
2) O/E or aberrant expression e.g. tyrosinase in melanoma, fetal proteins, and Cancer testis antigesn
3) products of oncogenic viruses
mechanisms of defence immunological
CD8+ T cells
NK cells
macrophages
limited role for antibodies
Evading defenses
1- loss of MHC 2- antigen-negative variants 3- immunosuppression TGFbeta 4- antigen masking 5- apoptosis of cd8 T cells
3 examples of benign tumors with adverse effects
1- hemangioma
2- leiomyoma
3- meningioma
paraneoplastic syndrome
a symptom that cannot be explained by a local or distant spread of the tumor
examples of paraneoplastic syndromes
1- ecctopic ACTH
2- ectopic adh- SCLC - siADH
3- hypercalcemia - squamous cell carcinoma
3 ways you may get hypercalcemia
1) parathyroid adenoma
2) bone mets
3) squamous cell lung carcinoma
cachexia characterized by
increased BMR
release of TNF IL-1
promote muscle catabolism
