Pathoma Ch. 3 - Neoplasia Basics Flashcards
Determining clonality in somatic cells vs. B cells
Somatic - G6PD isoform (normal = A:G 1:1)
B cells - Ig light chain (normal = kappa:lambda 3:1)
Leading causes of death in adults vs. children
Adults: Cardiovascular, cancer, cerebrovascular
Kids: Accidents, cancer, congenital defects
Why is lung cancer the most popular killer?
No good detection mechanism
Classes of oncogenes (w/ classic examples)
Growth factors (ex. PDGF-beta)
Growth factor receptors (ex. HER2, RET, KIT)
Signal transducers (ex. RAS, ABL)
Nuclear regulators (ex. Myc)
Cell cycle regulators (ex. cyclin D1, CDK4)
Classic tumor suppressor genes (w/ fxns of each)
P53 (slow G1 –> S cell cycle, upregulate DNA repair, and/or induce apoptosis via BAX if DNA damage can’t be repaired)
Rb (slow G1 –> S cell cycle by holding E2F inactive)
Rb phosphorylated vs. dephosphorylated
What inactivates it?
Phosphorylated = release E2F Dephosphorylated = hold E2F
Cyclin D/CDK4
What is true regarding the mutations for both p53 and Rb?
- Inactivating mutations
2. BOTH copies must be knocked out
Bcl overmutation
Result?
Follicular lymphoma
No apoptosis –> increased germinal centers, etc.
Overactive…
- PDGF-beta - RET - KIT - ABL - CKD4
Astrocytoma MEN2, Sporadic medullary thyroid cancer GIST CML, adult ALL Melanoma
Contaminated stored grains
Aflatoxins – HCC
Alcohol - cancers (4)
Oropharynx SCC, Upper esophagus SCC, Pancreas, HCC
Arsenic - cancers (3)
SCC of skin, Lung cancer, Liver angiosarcoma
Cigarette smoke - cancers (5)
Oropharynx, Esophagus, Lung, Kidney, Bladder
Smoked foods in japan
Nitrosamines - intestinal stomach cancer
Naphthylamine
Urothelial carcinoma of bladder
Vinyl chloride
Common route of exposure here
Angiosarcoma of liver
PVC pipe
Nickel, chromium, beryllium, or silica
Lung cancer
EBV
Nasopharyngeal carcinoma (Asia, Africa), Burkitt lymphoma (endemic), primary CNS lymphoma (AIDS)
HHV-8 in eastern european male
Treatment?
Kaposi sarcoma
Excise it
High risk HPV
SCC of vulva, vagina, anus, cervix
Adenocarcinoma of cervix
Ionizing radiation (Chernobyl, cancer)
AML, CML, papillary thyroid cancer (free radicals)
UVB sunlight
BCC, SCC, Melanoma (pyrimidine dimers)
Angiogenesis in cancers occurs via what?
FGF and VEGF
Tumor cells dissociate via ____
Tumor cells attach to ___ on BM and destroy it via ____
Tumor cells attach to ___ in the ECM to spread locally
Down-regulation of E-cadherin
Laminin; Collagenase (type 4 collagen destruction)
Fibronectin
IN GENERAL, carcinomas spread via ___
Exceptions? (4)
Lymphatics (regional LNs)
- RCC (renal vein)
- HCC (hepatic vein)
- Follicular thyroid carcinoma
- Choriocarcinoma (trophoblasts find BVs)
Classic characteristics of malignant tumors (7)
- Poorly differentiated
- Disorganized growth
- Nuclear pleomorphism
- Hyperchromasia
- High nuclear:cytoplasm ratio
- High mitotic activity w/ atypical mitoses
- Invasion (metastatic potential)
Cancer types…
- Keratin
- Vimentin
- Desmin
- GFAP
- Neurofilament
Epithelium Mesenchyme Muscle Neuroglia Neuron
Cancers…
- Thyroglobulin
- Chromogranin
- S-100
Thyroid FOLLICULAR cells
Neuroendocrine cells
Melanoma, LC Histiocytosis
Elevated serum tumor marker (ex. PSA)…must do what?
Biopsy
Low grade means ___
High grade means ___
Well-differentiated (looks like parent tissue)
Poorly-differentiated (does NOT look like parent tissue)
Which is more important: stage or grade?
Single most important prognostic indicator?
STAGE
Metastasis (M)
