CH4

uncontrolled growth - no regulation

individual cells, signal transduction, soluble factors that promote or inhibit growth

after cell proliferation with specific genes activated (differentiation)

autonomous, excessive, disorganized

clinical and histologic classification

expansile growth, capsule shaped, homogenous surface

vessel invasion, hemorrhage, nonhomogeneous cut surface

new features, not part of original tissue
undifferentiated, pleomorphism, N/C ratio, more cells undergoing mitosis, disorganized

malignant

malignant

benign

malignant

malignant

malignant

hyperchromatic nuclei takes up more stain than expected
indicates over active nuclear function

1. primary tumor
2. metastatic clone evolve
3. proliferation of the clone and invasion of vessel
4. transport into circulation (blood vessels)
5. embolization
6. invasion
7. new tumor formation at new site of metastasis

tumor induced angiogenesis

benign: -oma
malignant: -sarcoma

benign: -adenoma, papilloma
malignant: -carcinoma

tumor composed of fat cells (benign)

tumor is found to be composed of glands that appear uniform (benign)

SCC consists of solid cell nests that show central keratinization

presence of neoplastic glands

non neoplastic stroma

ganglioneuroma, neuroblastoma

glioma, meningioma

teratoma, embryonal carcinoma, seminoma / dysgerminoma

leukemia, lymphoma, mult myeloma

tumors composed of embryonic cells originating from embryonic primordia
ex. Retinoblastoma (eye), neuroblastoma (adrenal medulla or immature neural), hepatoblastoma (liver), nephroblastoma (kidney)

contains tissues formed from all 3 germ layers derived from germ cells
composed of various tissues intermixed in irregular manner

ectoderm, mesoderm, endoderm

based on clinical assessment during gross examination, surgery, x-ray, examinations, etc

size of tumor (T), presence of lymph node metastases (N), and distant metastases (M)

less differentiated and more adapted to survive under unfavorable conditions; require less oxygen to survive

cancer cells have less mitochondria, less RER, and less specialized enzymes
loss of highly specialized function

loss of highly specialized function

fetal protein or embryonic glycoproteins

alpha-fetoprotein (AFP), product of fetal hepatocytes, produced by liver cancer cells

carcinoembryonic antigen (CEA)

cells of large intestinal adenocarcinoma and normal fetal intestines

1. lack of contact inhibition
2. immortal: can be passed from one flask to another,
3. anchorage independent growth: in soft agar, roller bottles
4. autonomous growth: no growth factors

dependent on autocrine stimulation

chemical
physical
biologic (viruses?)

oncogenes (human cancer genes)
tumor suppressor genes

1. local action
2. at digestion & absorption in intestine
3. at metabolic activation in liver
4. at excretion in urine

carcinogen is absorbed preformed or as procarcinogen, then transformed to active carcinogen

1. initiation
2. promotion
3. conversion
4. progression
5. proliferation

irreversible genetic changes in exposed cells

initiated cells stimulate to proliferate (by continuous exposure)

cells proliferate on their own and convert to new cell type

get new genetic features and increased cell clones that do not change back after carcinogen or promoter has been removed

clonal expansion and mutations in unstable tumor cell genome leading to cell herogeneity

proliferation of divergent clones, selection of most vital clones

apoptosis / survival genes
angiogenesis invasion, progression genes
drug resistance genes

UV light
X rays
radioactive isotopes
atomic bomb

xeroderma pigmentosum and lack of DNA repair enzymes
abnormal DNA repair results in mutations

1. aflatoxin
2. Schistosoma haematobium
3. opisthorchis sinensis
4. human viral carcinogens

aspergillus flavus, acting as liver carcinogen

parasite acting as urinary bladder carcinogen

Chinese live fluke acting as bile duct or liver carcinogen

integration of DNA virus

integration, transduction, and insertion

actute-transofrming RNA viruses form cellular oncogenes

slow-transforming oncogenic viruses RNA viruses transform normal cell to malignant

virus inserts genome and activates latent cellular oncogene

integration
(e.g., HPV, EBV, HBV)

viral oncogenes (v-onc)

mutated proto-oncogenes

normal functions

1. point mutations
2. gene amplification
3. chromosomal rearrangement
4. insertion of viral oncogene

single base substitution in DNA chain

cell acquires increased number of proto-oncogenes
leads to overproduced normal protein

translocation of chromosomal fragment into another
deletion of fragment of chromosome
leads to overproduced or oncogenic fusion protein

leads to juxta positioning of genes
e.g., C-MYC gene and immunoglobulin gene (Burkitt's Lymphoma

insertion of viral genome, insertional mutagenesis of typically slow-transforming viruses
leads to oncogenic protein

leads to activation of myc oncogene
IG gene acts as promoter, lymphoma because active in lymphocytes

protect cells against activated or newly acquired oncogenes, suppresses oncogene

P53, BRCA1, BRCA2, RB1

codes for a protein that regulates cell cycle, therefore functions as tumor suppression

patients only born with one RB-1 gene. Mutation of remaining gene makes retina susceptible to cancer

persons born with both RB1 alleles, but both alleles must be inactivated or mutated

malignancy

lymphocytes (T, B, and NK cells), mq, and PMN

some tumors can regress spontaneously under the influence of immune factors

treated bladder cancer

carcinoembryonic antigen (CEA), and alpha-fetoprotein (AFP)

marker for adenocarcinoma of colon and other sites

marker for hepatocellular carcinoma and certain germ cell tumors that contain yolk sac components

type
location
histologic grade
clinical stage
immunity of host
sensitivity to therapy

causes narrowing of the lumen or obstruction

malignant tumor releasing hormone or protein that affects certain body system
or
when antibody to kill the tumor also damages system

Cushing's syndrome
hypercalcemia
polycythemia
venous thrombosis
myasthenia gravis