Patho Cancer Exam

Exam 4

cancer is a genetic disease

something has changed in DNA to allow these cells to grow

they divide rapidly, cells that don’t follow normal rules

removes the “brakes” on normal cells/pushes the gas

cancer is…

abnormal cells

neoplasm

new growth

abnormal mass of tissue that grows d/t cells dividing

some are malignant or benign

carcinogensis

how the normal cell becomes cancerous

step by step process

naming cancers

cancers are named based on where they are/located

carcinomas

epithelial tissue

adenocarcinomas

glandular tissue

sarcomas

connective tissue

lymphomas

lymphatic system

leukemias

blood/blood forming cells

cellular speacialization

body has highly specialized cells with specific jobs that don’t change

ex. RBC - carry’s O2

neurons - conduct impulses

muscle cells - muscle contracts

differentiated cells (cellular specialization)

mature specialized cells

should look like the tissue that they come from

normally do divid (“well behaved")

undifferentiated cells (cellular specialization)

immature/privative cells

don’t have a specific job yet

they divide rapidly to get to their tissue

this is where cancer can step in and take over

cellular adaption

understand how cancer works

cells adapt under stress

if have to constantly adapt, they lose function

atrophy (cellular adaption)

cell is shrinking

not cancer related

can happen normally/part of adaptation

hypertrophy

cells are getting bigger

number of cells are increasing in size

reversible once that stress is removed

hyperplasia

more cells (increase in number of cells)

cancer risk

cells are normal, just too many of them

metaplasia

way for cells to adapt

ex. ciliated cells in lungs

a smoker destroys those cells and turns them into squamous cells

these don’t function the same (have structure tho)

dysplasia

abnormal cell growth and organization

precancerous state

disorganized, dividing more rapidly than they should

step before cancer cells

anaplasia

lose all differentiation

divides rapidly

aggressive cells

major causes of cellular injury

1. inflammation and immunity

2. genetic disorders

3. nutritional imbalance

4. environmental factors

5. hormones

inflammation and immunity

inflammation - damages cells over time

immunity - chronic infection/autoimmune put cells at higher cancer risk

genetic disorders

cells are not functionally normal

come from our parents

repair mechanisms not efficient

nutritional imbalance

cells need the right fuel (too little or too much in imbalance)

protein and vitamin deficiency has low fuel

fats and glucose have too much fuel

environmental factors

smoke

sun

radiation

toxins

directly damage own

hormones

control cell growth

too many - excessive cell growth

too low - cellular atrophy

cellular death

1. apoptosis

2. necrosis

apoptosis

clean, controlled, and normal

programmed cell death

cell will shrink, break apart, and get cleaned up

necrosis

messy, damaging

cellular death not planned

cells swells and bursts - see inflammation and tissue damage

benign tumors

not cancer, abnormal growth

benign tumor characteristics

slow growing (takes months to years)

encapsulated (stay contained, don’t spread)

does not invade (increased pressure by pushing on things)

does not metastasize (don’t travel through blood, lymph, tissue)

resembles tissue of origin (well differentiated, organized)

less tissue damage

damage that can be caused by benign tumors

can cause airway issues/pain

pressure - push on nerves/vessels

ex. brain tumor can increase ICP

thyroid tumor can push on esophagus which leads to difficulty swallowing

malignant tumors

cancer tumors

malignant tumor characteristics

grow rapidly (divide d/t losing normal control and growth)

undifferentiated (don’t look like normal tissue, primitive, less differentiated - more aggressive cancer)

nonencapsulated

invades surrounding tissue

destroys local tissue and compression of blood vessels leading to tissue necrosis (can see pain, organ dysfunction) - slowing or omitting blood flow - leads to ischemia

stimulate angiogenesis (form new blood vessels and form their own blood supply - helps survival and spreading of cells)

normal cells

need permission to grow

only divid when told to divide

require growth signals

when signal stops, dividing stops

cancer cells remove control

sustained proliferative signaling mechanisms (cancer cells)

overproduction of growth factors

increased growth factor receptors on cell surface

mutated signaling proteins (normal signal pathway is broken)

autocrine signaling (self stimulation) (cancer cell releases own growth factor and responds to own growth factor)

immune surveillance and cancer normal role

identify abnormal cells

destroy cells

immune surveillance hypothesis

immune system in constantly preventing cancer

tumor strategies

hiding antigens (change surface of antigen so immune system can’t see them)

producing immunosuppressive signals (suppressing T-cells, inhibit immune response, blocking immune system)

tumor-suppressor genes (anti-oncogenes)

we want these

stop uncontrolled growth

slow down cell division

repair DNA

trigger apoptosis

when lost, cancer risk increases

oncogenes

abnormal

TP53 (“guardian of the genome”)

gatekeeper

most important tumor suppressor gene

detects DNA damage

triggers apoptosis if cells are abnormal

if mutated, cells will continue to grow leading to cancer

caretaker genes

repair DNA

maintain genetic stability

tumor suppressor genes

both prevent cancer

gate keeper - control cell growth

care taker - repair cell damage

ocogenesis

formation of cancer

pathway of oncogenesis

normal cell - DNA damage - DNA can repair genes (fix the problem) or fails to fix problem

failure of DNA repair - mutation in cell genes

mutation in cell genes can lead to:

1. activation of growth promoting oncogenes - increased rate of cell growth and proliferation (increase division of cells, ignore stop signals)

2. activation of apoptosis controlling genes (supposed to be turned off) - unregulated cell growth and proliferation (supposed to be stopped but continue to divide) - malignant neoplasm

3. loss of growth suppressing anti-oncogenes - unregulated cell growth and proliferation (supposed to be stopped but continue to divide) - malignant neoplasm

genomi instability

cell DNA becomes prone to mutations

when system fails, mutation continues to accumulate

genomic instability causes

mutations in TP53 and caretaker genes

chronic inflammation

radiation exposure

broca gene 1 + 2 (mutations cause breast cancer)

toxins/chemical/carcinogens

enabling replication immortality (cancer cell immortality)

normally cells can only divide a limited amount of times (ex. age)

cancer cells DO NOT

telomeres

protective caps on the end of chromosomes

with every divide, caps get shorter and cells stop dividing

cancer cells can activate telomerase

telomerase is an enzyme that rebuilds telomeres

prevent shortening, allowing continuous cell division, never reaches its limit

why does this matter? (telomerase in cancer)

cells divide indefinitely

cells avoid apoptosis and continue to grow

makes cancer mortality high

chronic inflammation and cancer risk

chronic inflammation is important in development of cancer (helps cancer grow)

it causes DNA damage and damage to growth signals

this increases risk of cancer/cellular mutation

causes of chronic inflammation

smoking

irradiation

environmental exposure

infection

tumor-associated macrophage (TAMs)

destroy abnormal cells

they get recruited into tumors, pull into tumor, and help the tumor

how do abnormal TAMs promote cancer?

help cancer grow, protect tumor

promote growth factors

stimulate angiogenesis

activating invasion and metastasis

spread of cancer from primary tumor through blood, lymph system, and body cavities

steps in metastasis

1. local invasion - tumor grow into local tissues

2. intravasation - cells enter blood/lymph system

3. circulation - cells moving through all systems

4. extravasation - cells push out of vessels themselves

5. colonization - new tumor will develop

mechanisms of action (metastasis)

decreased cell adhesion (break away from cells)

protease enzymes (help breakdown tissue)

increased motility (cells are moving)

angiogenesis (creating own blood cell)

immune evasion (can survive d/t immune system not seeing them)

angiogenesis

growth of new vessels

reroute the blood

cancer cells create their own

why does tumor induced angiogenesis matter?

allows tumor to suck in O2 and nutrients

can grow bigger and get rid of own waste

gives it a way to get in blood stream

tumor induced angiogenesis key drivers

vascular endothelial growth factor (stimulate new vessel growth)

tumor induced angiogenesis clinical revelance

use meds to help starve tumor by stopping angiogenesis

cancer staging

where the cancer is

purpose is to help plan treatment

gives survival expectations

cancer staging system used

TNM system

1. T (tumor) - size and extent of tumor

2. N (nodes) - has it pulled in the lymph nodes

3. M (metastasis) - has it spread to distant sites

carcinoma in situ

means in place

type of cancer where they found abnormal cells where they started

stage 1-4

stage 1 - localized, early (same tissue of where it started)

stage 4 - metastatic, advanced

grading of cancer purpose

grading of differentiation

how abnormal cells look/how bad cells look

grading

higher grade means more aggressive cancer

grade 1

well differentiated (low grade)

better prognosis if caught now

grade 2

moderately differentiated (intermediate grade)

grade 3

poorly differentiated (high grade)

grade 4

undifferentiated (high grade)

poor prognosis

tumor markers

substances that are produced by cancer cells

ex. hormones, protein

how are tumor markers used

can not confirm cancer itself***

1. monitoring treatment response

2. detect reoccurrence (might come before s/s appear)

3. support diagnosis

issues with using tumor markers

can be elevated with no cancer

some cancer doesn’t produce them

cancer can share same markers

breast cancer tumor markers

CA125

CEA

HER2

prostate cancer tumor markers

PSA

ovaries cancer

CA125

CEA