• cause genetic damage to cells
• examples
  • chemical carcinogens
  • radiant energy
  • oncogenic viruses, microbes

1. initiation (permanent damage to DNA)
2. promotion (induces tumors in initiated cells, but can't cause cancer alone; reversible)

Some initiating agents are direct while others require met. to ultamate carcinogens before they can act on DNA to produce damage

• exogenous agents (ex: cigarrette smoke, drugs, alcohol)
• endogenous agents (ex: hormones, bile acids)

Tumor promotion is reversible (Ex: reverse lung damage by smoking cessation)

1. normal cells acted on by initating agent
   1. DNA repair in tact and goes back to normal cells
   2. without DNA repair, apoptosis initiated
   3. w/o DNA repair or apoptosis, some of the cells are pre cancerous
2. the pre cancerous cells are acted on by a promoter (ex: alcohol, smoke, bile acids)
3. this causes proliferation and clonal expansion of mutated cells
4. addition insults will cause malignant tumor

• UV radiation increases cutaneous cancer incidence
• UVB (280-320) and UVC light (200-280) are mutagenic
• UVC filtered by ozone
• UVB cause pyrimidine dimers in DNA
• dimers repaired by nucleotide excision, but excessive sun exposure overwhelms path (Xeroderma Pigmentosum)

• leukemia
• thyroid cancer in young people
• solid tumors (post radiation breast angiosarcoma)
• ex: X ray, gamma rays, particulate radiation

• HPV
• Hep B (hepatocellular carcinoma)
• Epstein Barr virus
• Human T cell leukemia virus type one (T cell leukemia/lymphoma)
• Helicobacter pylori (gastric lymphoma)

• HPV 6, 11 are low risk assoc. with genital warts
• other HPVs are high risk and found in 85% in invassive cell carcinomas of cervix and precursors

African Burkitt lymphoma

B cell lymphoma in immunosup.

nasopharyngeal carcinoma

• tumor specific (present only on tumor cells)
• tumor associated (present on tumor cells and some normal cells)

• source
  • normal cellular proteins abnormally expressed in tumor cells
  • produced by oncogene virus
  • normally present on cells of origin (differntiation Ag's)
• levels- at high levels in cancer cells and normal fetal tissues, but not on adults

• in presence of antigen, CD8 T cells activated (MAJOR)
• other mechanisms:
  • NK cells
  • macrophages
  • Ab's (complement, ADCC)

• select for Ag negative variants
• reduced expression of MHC molecules (trigger NK cells)
• lack of co stimulation
• immunosupprssion of host (produce TGF beta)
• Ag masking by glycocalyx molecules (ex: sialic acid containing mucopolysaccharides)
• death to cytotoxic T cells

• location
• functional activity
• erosive growth of ulceration, bleeding and secondary infection
• acute symptoms caused by rupture or infarction
• cachexia (probably due to TNF)
• paraneoplastic syndrome

• pituitary adenoma (due to location) compresses optic nerve causing bitemporal heminopsia
• pituitary adenomas produce hormones which cause clinical symptoms like galactorrhea

• elaboration of hormones or factors secondary to tumor progression (commonly endocrinopathies)
• syndrome often resolves after tx of underlying tumor

• cancers
  • small cell carcinoma of lung
  • pancreatic carcinoma
  • neural tumors
• mechanism- ACTH or ACTH like substances

• underlying cancer
  • small cell carcinoma of lung
  • intracranial neoplasms
• mechanism- ADH and ANF

• underlying cancer
  • squamous cell carcinoma of lung
  • breast carcinoma
  • renal carcinoma
  • adult T cell leukemia/lymphoma
  • ovarian carcinoma
• mechanism
  • PTHRP
  • TGF alpha
  • TNF
  • IL-1

• underlying cancer
  • carcinoid tumor
  • gastric carcinoma
  • pancreatic carcinoma
• mechanism
  • serotonin
  • bradykinin
  • histamine

• def.- level of differentiation or how closely the tumor functions as and resembles its cell of origin
• evaluated by:
  • cell size and shape
  • N:C ratio
  • mitotic activity
  • organization of tissue
  • presence of necrosis
  • presence of lymphovascular invasion

• def.- distribution and extent of cancer at time of dx
• all staging systems evaluate:
  • size of primary lesion
  • extent of spread to regional lymph nodes
  • presence or absence of metastases
• staging aids in selection of best therapy for the patient

Stage has greater clinical value than grade.

• clinical history
• phy examination
• radiological imaging
• lab tests
• examine tissue

• surgical methods
  • rapid frozen section (freezing allows us to cut thin section and allows rapid examination and processin at time of surgery)
  • biopsy
  • excision
  • resection
• cytologic methods (allows us to examine individual cells)
  • fine needle aspiration
  • smears
• immunohistochem
• ultrastructural examination (electron microscopy)
• molecular methods (FISH, PCR)
• flow cytometry

1. special stains that utilize Ab binding to specific Ag in tissue
2. binding visualized through use of various enzymes coupled to Ab use
3. enzymes acts upon chromogenic substrate to cause deposition of colored material at the site of Ag-Ab bindings
4. colored material visualized by light microscopy

• classify undifferentiated malignant tumors
• classify leukemias and lymphomas
• determine site of origin of metastatic tumors
• detect molecules that have prognostic or therapeutic sign. (ex: ER, PR, and HER-2 in breast cancer)

• confirm dx
• aid in tumor staging
• determine response to therapy or presence of recurrent disease

• def.- biochemical indicators of presence of a tumor (ex: cell surface Ag's, hormones, proteins)
• can be detected in plasma, serum, body fluids

• trophoblastic tumors
• non seminomatous testicular tumors

• hepatocellular cancer
• testicular tumors