CH3.txt

new tissue growth that is unregulated, irreversible, and monoclonal

unregulated, irreversible, and monoclonal

that the neoplastic cells are derived from a single mother cell

glucose-6-phosphate dehydrogenase (G6PD) enzyme isoforms.

G6PDA, G6PDb, and G6PDc exist; only one isoform is inherited from each parent.

In females, one isoform is randomly inactivated in each cell by lyonization

X

1:1 (e.g 50% of cells have G6PDa , and 50% ofcells have G6PDG)

1:1 ratio is maintained in hyperplasia, which is polyclonal (cells are derived from multiple cells).

Only one isoform is present in neoplasia, which is monoclonal

androgen receptor isoforms, which are also present on the X chromosome.

immunoglobulin (Ig) light chain phenotype.

heavy and light chains.

light chain that is either kappa or lambda.

3:1.

This ratio is maintained in hyperplasia, which is polyclonal

Ratio increases to > 6:1 or is inverted (kappa to lambda ratio = 1:3) in lymphoma, which is monoclonal

benign or malignant

remain localized and do not metastasize

(cancer) invade locally and have the potential to metastasize.

lineage of differentiation (type of tissue produced) and whether the tumor is benign or malignant

Adenoma, papilloma

Adenocarcinoma and papillary carcinoma

Lipoma

Liposarcoma

Does not exist

Lymphoma/Leukemia

Nevus (mole)

Melanoma

cancer

(1) cardiovascular disease (2) cancer (3) cerebrovascular disease

(1) accidents (2) cancer (3) congenital defects

(1) breast/prostate (2) lung (3) colorectal.

(1) lung (2) breast/prostate (3) colorectal

single mutated cell.

30

will have undergone additional divisions and, hence, additional mutations.

tend to have a poor prognosis.

to catch dysplasia (precancerous change) before it becomes carcinoma or carcinoma before clinical symptoms arise.

1. Pap smear 2. Mammography 3. PSA and DRE 4. Hemoccult test and colonoscopy

detects cervical dysplasia (GIN) before it becomes carcinoma

detects in situ breast cancer (e.g DOS) before it invades or invasive carcinoma before it becomes clinically palpable

Prostate specific antigen (PSA) and digital rectal exam detects prostate carcinoma before it spreads

for occult blood in stool

detect colonic adenoma before it becomes colonic carcinoma or carcinoma before it spreads

damage to DNA of stem cells. The damage overcomes DNA repair mechanisms, but is not lethal.

agents that damage DNA, increasing the risk for cancer.

chemicals, oncogenic viruses, and radical ions

key regulatory systems, allowing for tumor promotion (growth) and progression (spread)

proto-oncogenes, tumor suppressor genes, and regulators of apoptosis

cell growth and differentiation;

oncogenes that lead to unregulated cellular growth.

growth factors, growth factor receptors, signal transducers, nuclear regulators, and cell cycle regulators

cellular growth (e.g PDGFB in astrocytoma),

mediate signals from growth factors (e.g. ERBB2 HER2/neu in breast cancer).

Relay receptor activation to the nucleus (eg. ras)

growth factor receptors in an inactive GDP-bound state.

Hepatocellular carcinoma Derived from Aspergillus, which can contaminate stored grains

leukemia/lymphoma side effect of chemotherapy

Squamous cell carcinoma of oropharynx and upper esophagus, pancreatic carcinoma, and hepatocellular carcinoma

Squamous cell carcinoma of skin, lung cancer, and angiosarcoma of liver. Arsenic is present in cigarette smoke.

Lung carcinoma and mesothelioma. Exposure to asbestos is more likely to lead to lung cancer than mesothelioma.

Carcinoma of oropharynx, esophagus, lung, kidney, and bladder. Most common carcinogen worldwide; polycyclic hydrocarbons are particularly carcinogenic.

Stomach carcinoma, Found in smoked foods, responsible for high rate of stomach carcinoma in japan

Urothelial carcinoma of bladder. Derived from cigarette smoke

Angiosarcoma of liver, occupational exposure; used to make polyvinyl chlurkle (PVC) for use in pipes

Lung carcinoma Occupational exposure

EBV, HHV-8, HBV and HCV, HTLV-1, High-risk HPV

Nasopharyngeal carcinoma, Burkitt lymphoma and CNS lymphoma in AIDS

Kaposi sarcoma

Hepatocellular carcinoma

Adult T-cell leukemia/lymphoma

Squamous cell carcinoma of vulva, vagina, anus, and cervix; adenocarcinoma of cervix

(nuclear reactor accidents and radiotherapy) AML, CML and papillary carcinoma of the thyroid. Generates hydroxyl free radicals.

Basal cell carcinoma, squamous cell carcinoma, and melanoma of skin

formation of pyrimidine dimers in DNA, which are normally excised by restriction endonuclease

GDP to be replaced with GTP, activating ras.

sends growth signals to the nucleus

inactivates itself by cleaving GTP to GDP; this is augmented by GTPase activating protein

inhibits the activity of GTPase activating protein. This prolongs the activated state of ras, resulting in increased growth signals.

progression through the cell cycle (e.g. cyclin and cyclin-dependent kinase).

form a complex which phosphorylates proteins that drive the cell through the cell cycle.

phosphorylates the retinoblastoma protein, which promotes progression through the G-S checkpoint

Regulate cell growth decreasing (suppress) the risk of tumor formation;

p53 and Rb (retinoblastoma)

progression of the cell cycle from G to S phase

slows the cell cycle and upregulales DNA repair enzymes.

Platelet-derived growth factor, overexpression, autocrine loop, astrocytoma

Epidermal growth factor receptor, Amplification mechanism, Subset of breast carcinomas

Neural growth factor receptor, Point mutation MEN 2A, MEN 2B and sporadic medullary carcinoma of thyroid

Stem cell growth factor receptor, Point mutation, Gastrointestinal stromal tumor

GTP-binding protein, Point mutation, Carcinomas, melanoma, and lymphoma

Tyrosine kinase T(9;22) with BCR CML and some types of ALL

C-MYC, N-MYC, L-MYC

Transcription factor, t(8;I4) involving IgH, Burkitt lymphoma

Transcription factor, Amplification, Neuroblastoma

Transcription factor, Amplification, Lung carcinoma (small cell)

Cyclin t(8;14) involving IgH, Mantle cell lymphoma

induces apoptosis.

upregulates BAX, which disrupts Bcl2 leading to cytochrome c leaks from the mitochondria activating apoptosis

both copies of the p53 gene must be knocked out for tumor formation, Both copies of Rb gene must be knocked out for tumor formation

>50% of cancers.

Li-Fraumeni syndrome (2nd hit is somatic),

the propensity to develop multiple types of carcinomas and sarcomas,

regulates progression from G0 to S phase.

holds the E2F transcription factor, which is necessary for transition to the S phase

RB is phosphorylated by the cyclinD/cyclin-dependent kinase 4 (CDK4) complex

constitutively free E2F, allowing progression through the cell cycle and uncontrolled growth of cells.

(both hits are somatic) and it is characterized by unilateral retinoblastoma

familial retinoblastoma (2nd hit is somatic) and is characterized by bilateral retinoblastoma and osteosarcoma.

Prevent apoptosis in normal cells, but promote apoptosis in mutated cells whose DNA cannot be repaired (e.g Bcl2)

normally stabilizes the mitochondrial membrane, blocking release of cytochrome c

Cytochrome c to leave the mitochondria and activate apoptosis

it is overexpressed in follicular lymphoma,

t(14;18) moves Bcl2 (chromosome 18) to the Ig heavy chain locus (chromosome 14), resulting in increased Bcl2.

Mitochondrial membrane is further stabilized by overexpressed Bcl2, prohibiting apoptosis.

B cells that would normally undergo apoptosis during somatic hypermutation in the lymph node germinal center accumulate, leading to lymphoma.

Telomerase

shorten with serial cell divisions, eventually resulting in cellular senescence

cancers often have up regulated telomerase, which preserves telomeres

(production of new blood vessels) is necessary for tumor survival and growth.

(angiogenic factors) are commonly produced by tumor cells.

Avoiding immune surveillance is necessary for tumor survival

Mutations often result in production of abnormal proteins, which are expressed on MHC class 1, CD8+ T cells detect and destroy such mutated cells, Tumor cells can evade immune surveillance by downregulating expression of MHC class 1.

by downregulating MHC class 1

(both primary and secondary) increases risk for cancer

tumor invasion and spread

cellular adhesion molecules (e.g., E-cadherin).

dissociation of attached cells

Cells attach to laminin and destroy basement membrane (collagen type IV) via collagenase. Cells attach to fibronectin in the extracellular matrix and spread locally

Entrance into vascular or lymphatic spaces allows for metastasis (distant spread)

Lymphatic, hematogenous, seeding of body cavities

carcinomas

In the regional draining lymph nodes

sarcomas and some carcinomas

renal cell carcinoma, hepatocellular carcinoma, follicular carcimoma of the thyroid, choriocarcinoma

ovarian carcinoma, often involves the peritoneum 'omental caking'

where the peritoneum is often involved in ovarian carcinoma

tend to be slow growing, well circumscribed, distinct, and mobile

rapid growing, poorly circumscribed, infiltrative, and fixed to surrounding tissues and local structures.

Biopsy or excision

Some benign tumors can grow in a malignant-like fashion, and some malignant tumors can grow in a benign-like fashion.

well differentiated

1. Organized growth 2. Uniform nuclei 3. Low nuclear to cytoplasmic ratio 4. Minimal mitotic activity 5. Lack of invasion (of basement membrane or local tissue) 6. No metastatic potential

poorly differentiated (anaplastic)

1. Disorganized growth (loss of polarity) 2. Nuclear pleomorphism and hyperchromasia 3. High nuclear to cytoplasmic ratio 4. High mitotic activity with atypical mitosis 5. Invasion (through basement membrane or into local tissue)

Metastatic potential - benign tumors never metastasize

Epithelium

Mesenchyme

Muscle

Neurons

Prostatic epil helium

Breast epithelium

thyroid follicular cells

neuroendocrine cells (small cell carcinoma of lung and carcinoid tumors)

Melanoma

Immunohistochemistry

Proteins released by tumor into serum (e.g PSA)

screening, monitoring response to treatment, and monitoring recurrence

it requires tissue biopsy for diagnosis of carcinoma (e.g., biopsy of prostate with elevated PSA),

Microscopic assessment of differentiation (how much a cancer resembles the tissue in which it grows); takes into account architectural and nuclear features

Well differentiated—resembles normal parent tissue

poorly differentiated—does not resemble parent tissue

determining prognosis; well-differentiated cancers have better prognosis than poorly-differentiated cancers.

its an assessment of size and spread of a cancer,

Key prognostic factor; more important than grading

after final surgical resection of the tumor

T—tumor (size and/or depth of invasion), N—spread to regional lymph nodes; second most important prognostic factor, M—metastasis; single most important prognostic factor

Metastasis