neoplasm 6 Flashcards
describe radiation carcinogenesis
- Skin cancer = basal cell carcinoma, squamous cell carcinoma, MELONOMA
MECHANISM: - pyrimidine dimers –> DNA damage
- normal DNA repair - NER pathway (nucleotide excision repair)
- individuals with enzyme defects mediating DNA repair are particularly susceptible (xeroderma pigmentosum)
describe ionizing radiation
- direct effect
- indirect effect via free radicals
- increased risk with higher dose or high LET
- MECHANISMS = chromosome breakage, translocation and point mutation
define atomic bomb cancers
- normally occurs Leukemias (except CLL)
- also causes Thyroid cancer (papilary type)
- breast/lung cancer (less common)
- Skin, bone, gut are LEAST susceptible
Define X ray workers
- radiation dermatitis
- develop skin cancer
what type of cancer does painting dials of watches with lumnious radium cause
- osteosarcoma
describe teh pathogenesis of hepatitis B in causing cancer
- Chronic liver cell injury and regenerative hyperplasia
- encodes regulatory protein HBx protrein that is responsible for:
- -> activating growth promoting genes (insulin-like GF)
- -> binds to p53 (inhibition)
- causes hepatocellular carcinoma
describe the pathogenesis of hepatitis C in causing cancer
- chronic liver cell injury and regeneration
- causes hepatocellular carcinoma
describe Epstein-Barr virus as it is releated to cancer
- Associated neoplasms
- -> burkitt lymphoma
- -> hodgkin lymphoma
- -> B-cell lymphoma in immunosuppressed patients
- -> nasopharyngeal carcinoma
describe HPV as it is related to cancer
- HPV 6 and 11 = low risk episomal (non-integrated form) –> cause benign squamous papiloma (warts)
- HPV 16,18,31 = high risk; viral DNA integrated in host genome (E6 inhibits p53; E7 inhibits Rb)
describe Human T-cell leukemia virus Type 1 (HTLV-1)
- Causes T-cell leukemia/lymphomas
- Mode of transmission = intercourse, blood, breast feeding
- Pathogenesis = CD4 tropism
- Contains Tax gene:
1) stimulates transcription of viral mRNA
2) activates c-Fos, IL-2(T-cell GF) and FM-CSF = all involved in proliferation
3) inactivates p16INK4a (is an anti-proliferative molecule)
Describe HIV as it is related to cancer
- causes lymphoma
- human herpes virus 8 (HHV-8) causes kaposi sarcoma
- -> associated with HIV
describe how H. Pylori is releated to cancer
- Assocaited with gastric lymphoma (MALT lymphomas), and Gastric carcinoma
- CONTAINS CagA (cytotoxin associated gene A) which stimulates growth factor pathway
describe estrogen
- related to breast cancer, squamous cell carcinoma of cervix and leiomyoma of uterus
how to determine between benign and malignant
- benign have a capsule
describe contraceptive hromoens
- assocaited with breast cancer and benign/malignant liver tumors
describe anabolic steroids
-associated with benign/malignant liver tumors
describe cancer cachexia
- clinical feature in a patient with a tumor
- loss of body fat, wasting and profound weakness
- CAUSED by TNF being produced
- symptoms are loss of appetite, metabolic changes
define para-neoplastic syndromes
- distant effects of a tumor unrelated to primary tumor or metastasis
- may represent earliest manifestation of a cancer
describe examples of para-neopalstic sydnromes
- endocrinopathies –> lung cancer secretes ACTH which devels cushing syndrome and diabetes resulting in wt loss, hypertension, hyperpigmentation (due to ACTH)
- Hyponatremia/SIADH = small cell carcinoma lung secretes ADH causes too much water to be in the body leading to HYPOnatremia
describe Acnathosis nigricans
- example of para-neoplastic syndrome
- causes a black, verrucoid appearing lesion of the skin (usually located in axilla)
- associated with GASTRIC CARCINOMA
- -> also another skin lesion associated with stomach carcinoma is leser-trelant sign (multiple, outcroppings of pigmented seborrheic keratosis
describe Carcinoid syndrome
- assocaited with carcinoid tumors (neuro-endocrine tumors)
- tumor location is found in appendix or small intestine
- PRODUCES SEROTONIN
- CLINICAL FEATURES = flushing, diarrhea, bronchospams, tachycardia
- DIAGNOSED by urinary excretion of 5-hydroxy-indoleacetic acid, a metabolite of serotonin
describe hypercalcemia
- malignancy accounts for 40% of all cases of hypercalcemia
- causes for hypercalcemia in malignancy
- -> RELEASE OF PTH related peptide CAUSES Squamous cell carcinoma of lung or Renal cell carcinoma
- -> osteolytic bony metastasis (release of osteolytic factors PGE2, IL-1) cause breast cancer
describe Hypocalcemia
- produces CALCITONIN
- develops into medullary carcinoma of thyroid
describe gynecomastia
- produces hormone Beta-HCG
- assocaited with choriocarcinoma testis
describe eaton-lambert syndrome
- Myasthenia gravis-like syndrome
- assocaited with SMALL CELL CARCINOMA OF LUNG
when should you use IHC to diagnose cancer
- diagnosis of undifferentiated tumors
- categorization of leukemias and lymphomas
- to determine site of origin of metastasis
- detecting molecules having prognostic or therapeutic significance
how would you know that a tumor is epithelial in origin
- if the tumor is POSITIVE for CYTOKERATIN, keratin or eptihelial membrane antigen (EMA), indicates an epithelial origin.
what marker is used in mesenchymal origin
- vimentin (some mesenchymal origin)
- desmin; muscle-specific actin (origin-muscle)
what markers are used in LCA
- leukocyte common antigen
- origin - leukocytes
what markers are used in neuronal tumors
- Non-specific enolase (NSE)
- -> neuroendocrine tumors such as SMALL CELL CARCINOMA of the lung and carcinoids stain with NSE
- chromogranin
- synaptophysin
what is a tumor marker
- a tumor marker is a sustance found in blood, urine, or body tissue that can be elevated in cancer, among other tissue types
What does increase in carcino-embryonic antigen (CEA) indicative of
- carcinomas of colon, pancreas, stomach, breast
what does iincrease in prostate-specfic antigen (PSA) indicative of
- Prostate cancer
what does increase in beta-human chorionic gonadotropin (B-HCG) indicative of
- trophoblastic tumors (choriocarcinoma)
what does increase in CA-125 indicative of
- ovarian carcinoma
what does increase in alpha-fetoprotein (AFP) indiciative of
- hepato-cellular carcinomas
- germ cell tumors of testes or ovary
what does increase in NSE indicative of
- SMALL CELL CARCINOMA OF LUNG
what does incease in calcitonin indicative of
- medullary thyroid carcinoma
what does increase in CA 19-9 indicative of
- colon cancer, pancreatic cancer
what does increase in CA 15-3 indicative of
- breast carcinoma
