Cancer

Patho Exam 2

cancer word origin

derived from Greek word for crab - karkinoma - another name for malignant tumor

cancer definition

not a tumor, abnormal growth resulting from uncontrolled proliferation, serves no physiologic function , also referred to as neoplasm (new growth)

benign tumors

named according to tissue from which arise + suffix -oma (lipoma - fat , leiomyoma - smooth muscle)

malignant epithelial tumors

carcinomas (adenocarcinoma - ducts or glands)

malignant CT tumors

sarcoma

cancers of lymph tissue

lymphomas

cancers of blood forming cells

leukemias

benign v malignant tumor

slow growth, well defined capsule, noninvasive, well differentiated, low mitotic index, not metastasize

rapid growth, not encapsulated, invasive, poorly differentiated (anaplasia), high mitotic index, can metastasize (spread distantly)

Carcinoma in situ (CIS)

preinvasive epithelial malignant tumors of glandular or squamous origin, not broken through basement membrane or invaded surrounding stroma, not malignant (yet)

carcinoma in situ prognoses

1. remain stable for long time

2. progress to invasive and metastatic

3. regress and disappear

cancer is predominantly a disease of … because ….

aging, multiple mutations required before can develop

clonal proliferation or expansion

due to mutation, cell acquires characteristics that allow it to have selective advantage over neighbors, increased growth rate / decreased apoptosis

mutations

alteration in DNA sequence, effect expression/function of gene; point, driver, passenger types

point mutations

small scale changes

driver mutations

drive progression of cancer

passenger mutations

random events

gene amplification

repeated duplication of chromosome, 10s or 100s of copies made

chromosome translocation

large changes in chromosome structure, piece of one translocated to another

clonal proliferation/expansion

cancer cell progeny accumulate faster than nonmutant neighbors

malignant transformation

process normal cell becomes cancer , heterogenous mix of cancer cells

oncogenes

mutant genes that direct protein synthesis and cell growth in nonmutant state

tumor suppressor genes/ anti-oncogenes

encode proteins that negatively regulate proliferation in normal state

proto-oncogenes

normal nonmutant genes code for cell growth

genetic mechanisms w/ role in human carcinogenesis

1. activation of proto-oncogenes → hyperactivity of growth related gene products (oncogenes)

2. mutation of genes resulting in loss/inactivity of tumor suppressor genes

3. mutation of genes resulting in overexpression of products that prevent apoptosis (allowing continued tumor growth)

caretaker genes

responsible for maintenance of genomic integrity, encode proteins involved in repairing damaged DNA; loss of function leads to increased mutation rates, genomic instability, greater risk of cancer

genomic instability

CIN (chromosome instability) also appear increased in malignant cells, may be due to malfunctions in cell machinery that regulates chromosomal segregation at mitosis; results in high rate chromosomal loss, heterozygosity, chromosomal amplification (each of which can accelerate loss of tumor suppressor genes and overexpression of oncogenes)

cancer cell replication

body cells typically divide only limited number of times - Hayflick limit - and telomeres become smaller and smaller w/ each division ; cancer cells can activate telomeres leading to continued division

angiogenesis

neovascularization- new growth of vessels, advanced cancers can secrete angiogenic factors to facilitate feeding tumor - VEGF (vascular endothelial growth factor)

cancer metabolism

glycolysis; allows lactate and metabolites to be used for more efficient production lipids etc for rapid growth

inflammation as a cause of cancer

chronic inflamm - important factor in dev

active inflamm - predisposes person bc stimulate wound healing response → proliferation and angiogenesis

susceptible organs - GI tract, pancreas, thyroid, prostate, urinary bladder, pleura, integument

tumor associated macrophage (TAM)

key cell that promotes tumor survival - develops capacity to block cytotoxic T cell and NK functions , produce cytokines advantageous for growth and spread , secretes angiogenesis factors

tumor associated antigens

oncogenes , antigens from oncogenic viruses , oncofetal antigens , altered glycoproteins and glycolipids

immunotherapy

active - immunization w/ tumor antigens to elicit/enhance immune response against particular cancer

passive - inject pt dx w/ cancer w/ antibodies or WBCs directed against tumor associated antigens

viruses associated w/ cancer

HPV , EBV , KSHV or HHV8 (kaposi sarcoma herpesvirus) , HTLV-1 (human t cell lymphotropic virus type 1) , HBV (hep b) , HCV (hep c)

metastasis requirements

require cells have many new abilities - spread , survive (travel time) , proliferate (in distant locations) , destination receptive to growth of cancer

invasion

local spread , prereq for metastasis (1st step in process) , often spread to regional lymph nodes first then lymph system then distant organs via bloodstream ; requires cancer attach to specific receptors and survive in specific environment

protease

secreted by cancer cells , digest ECM and basement membranes (create pathways to move through)

paraneoplastic syndromes

sx complex triggered by cancer but not caused by direct/local effects of tumor mass , caused by bio substances released from or by immune response triggered by, can be fatal

cachexia

most severe form malnutrition , leads to protein calorie malnutrition and progressive wasting

manifestations - anorexia , early satiety , weight loss , anemia , asthenia , taste alterations , altered protein lipid carb metabolism

cancer staging

involves size, degree of invasion, and extent of spread

stage 1 - confined to organ of origin

stage 2 - locally invasive

stage 3 - advanced to regional structures

stage 4 - spread to distant sites

tumor markers

substances produced by benign or malignant cells , found on or in tumor cell , in blood , spinal fluid , or urine - hormones, enzymes, genes, antigens, antibodies

used to screen identify individuals high risk for cancer, dx specific types tumors, follow clinical course of cancer

liver and germ cell tumor markers

secrete protein AFP (alpha fetoprotein) into blood

prostate tumor markers

secrete PSA (prostate specific antigen) into blood

tumor markers w/ biologic activity

sx are expressed, phenomenon known as paraneoplastic syndrome occurs

pediatric cancer

most common are central nervous tremors and leukemias, most originate from mesodermal germ layer - give rise to CT, bone cartilage, muscle, blood, BV, gonads, kidneys, lymph system - often dx during peak times physical growth , usually fast growing and metastasized before dx made , higher incidence male than female

adolescent cancers

most common are lymphomas - Hodgkin and non-Hodgkin

embryonic tumors

originate during intrauterine life, immature embryonic tissue unable to mature or differentiate into fully developed cells, commonly named w/ suffix -blast

chromosome aberrations and single gene defects

aneuploidy, amplifications, deletions, translocations ; trisomy 21 linked to leukemia

HPV and cancer

types 16 and 18 cause majority of cancers, infect epithelial cells and mutations lead to cancer, associated w/ cervical and anal cancers, recently associated w/ cancers of oropharynx (soft palate, base of tongue, tonsils)

impact of infection

important contributor to cancer

HPV - cervical cancer

Hep B and C (together) - liver cancer

H. pylori - stomach cancers

EBV - nasopharynx and stomach, Hodgkin disease, non-Hodgkin lymphoma

herpes type 8 - kaposi sarcoma

t-cell lymphotropic virus type 1 - leukemia, lymphoma

ionizing radiation effects

damage to organs w/ high proliferative cells (skin , GI) , alters tumor microenvironment / immune system cells , long term risk of developing other cancers/diseases

associated w/ acute leukemias, increased freq thryoid and breast carcinomas, lung, stomach, colon, esophageal, urinary tract, multiple myeloma

indoor vs outdoor pollution

indoor worse

alcohol

carcinogen, increase risk oral cavity, pharynx, larynx, esophageal, liver, colorectal, breast cancers

nutriogenomics

study of nutrition on phenotypic variability of individuals based on genomic differences