Exam 2 - Neoplasia Flashcards
Benign macroscopic features
circumscribed, encapsulated
necrosis uncommon (slow growth)
more boundary
Metastatic macroscopic features
invasive into adjacent tissues necrosis common (fast growth) less boundary
Benign microscopic features
well differentiated (looks like origin tissue) low turnover less mitotic activity no invasion organized
Metastatic microscopic features
poor differentiation high turnover more mitotic activity invasion poor organization pleiomorphism
Hallmarks of Cancer
Evading apoptosis Self-sufficiency in growth signals Insensitivity to anti-growth signals Tissue invasion and metastasis Limitless replicative potential Sustained angiogenesis
Histologic Grade
Low = more differentiation, closer to normal
High = less differentiation, further from normal
Take into account mitotic activity/architectural features
Less reliable than disease stage
Tumor/Disease Stage
T: Tumor (is,1-4)
N: Regional LN (X, 0, 1, 2), where 1=1-3
M: Distant metastasis (X, 0, 1)
N,M relate more to prognosis
Three metastatic disseminations
Direct seeding (cavitary)
Lymphatic spread
Hematogenous spread
4 Steps of the metastatic cascade
- Invasion
- Intravasation
- Extravasation
- Colonization
Invasion (metastatic cascade)
- loss of E-cadherin, down regulated
- Degradation of BM/CT (cleaves/squeezes)
- De-attachment to ECM (should apoptose, don’t)
- Locomotion (protrusion, adhesion, translocation, retraction)
Epithelial to mesenchymal transition
Normal process used inappropriately by cancer cells
Ex: palate formation, neural crest fusion
EMT to undergo intravasation
MET to undergo extravasation
More M character = more aggressive
Metastatic organ preference
Prostatic carcinoma
Neuroblastomas
Prostatic= bone
Neuroblastoma= liver/bone
Seed and soil (environment)
Ewing’s mechanical arrest (stop in first capillary bed)
Cancer effects
Direct effects: invasive mass interference
Indirect effects: paraneoplastic syndrome (7-15%)
Paracrine/endocrine effects
Causes of death in cancer
- Infection (chemo)
- Organ Failure
- Hemorrhage
- Thromboembolism
- Emaciation
Emerging Hallmarks of Cancer
Deregulation cellular energetics
Avoiding immune destruction
Genome instability/mutation
Tumor-promoting inflammation
Environmental impact on cancer
- 80% caused by environmental factors
- Variation due to region/country
- Migrants/decendents adopt risk of new country
Most common cancer incidence men/women
- Prostate/breast
- Lung
- Colorectal
Most common cancer death men/women
- Lung
- Prostate/breast
- Colorectal
Ames test
Measures ability of chemical to mutate salmonella
His- agar, biosynth reveals mutation
Clear zone = toxic, ring = low dose/mutagenic
Animal testing conclusions on cancer
Effect is dose dependent
One carcinogen = one type cancer
Requires time/proliferation
Transmittable to daughter cells
Two step model of carcinogensis
Initation (mutagen, irreversible)
Promotion (nonmutagen, reversible, often inflammation or proliferation stimulating)
4 types of lung carcinoma
- Squamous
- Adenocarcinoma
- Large cell
- Small cell
Squamous cell carcinoma (lung)
Strongly linked to smoking
Occur centrally
Large, necrotic, hemorrhagic
Keratin pearls
Adenocarcinoma (lung)
Central or periphery (sometimes scarring)
Little stroma
Best prognosis
Large cell lung carcinoma
Pleomorphic, aggresive
Small cell lung carcinoma
Anywhere in lung
High grade cancer
Small, dark staining, + stain for neuroendocrine markers
Terrible prognosis
Risk Factors Lung Carcinoma
Pack years
Family fx
Industrial vapors
Risk Factors Pancreatic Carcinoma
Unknown!
Diabetes mellitus
Back pain, jaundice, cachexia
Colon carcinoma
Most sporadic,
Conditions that increase risk for colon carcinoma
FAP
Lynch Syndrome
MutY
Risk Factors Prostate Cancer
Age
Race
Genetics
Sunlight via Vit D?
PIN and Pca
Non-invasive precursors in prostate cancer Gleason grade (differentiation grade)
Primary chemotherapy
on it’s own
often palliative (sometime curative)
primary cancer treatment
Neoadjuvant therapy
before local therapy to make local more effective
easy to assess effects during local therapy
Adjuvant therapy
after local therapy, targets micromets
harder to assess from research pov
Classes of anti-tumor agents
DNA damaging Topoisomerase Microtubule interacting Hormonal Antibodies Kinase inhibitors
Common resistance mechanisms
Drug efflux (common) Resistance to apoptosis (common) Mutations in drug target (specific) Activation of repair enzymes (specific) Other ways to activate receptors (specific)