term1 Definition1term2 Definition2term3 Definition3
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Benign tumors?
do not develop subsequent mutations-> retain well-controlled growth, benign histologic features.
Malignant tumors?
develop subsequent multiple mutations, overexpressions acqured enzyme pathways (telomerases), loss of cell adhesion markers.
devleop capacity for invasion and metastasis.
acquire gross microscopic features of malignancy.
Evolution of malignant melanoma?
benign nevus(benign limited growth, BRAF mutation)->
dysplastic nevus(premalignant, lesions may regress, random atypia, CDKN2A loss, PTEN loss)->
radial-growth phase(dec differentiation, unlimited hyperplasia, connot grow in soft agar, clonal proliferation, inc CD1)->
vertical-growth phase(crosses BM, grows in soft agar, forms tumor, Ecad loss, Ncad expression, alphaVbeta3 integrin expression, MMP2 expression, survivin, reduced TRPM1)-> metastatic melanoma(dissociates fr primary tumor, grows at distant sites, absent TRPM1).
RAS activation pathway?
GAPs (GTPase-activating proteins).
Active RAS->PI3K-AKT-mTOR-activation of transcription-MYC protein-cell cycle progression. or RAF-MAPK.
GFR's?
ERBB1?
HER2/NEU (ERBB2)?
GFR's-overexpression (amplification)->cancer cells hyperrespond to levels of GF's.
ERBB1 (EGF receptor) -overexpressed in 80% sq. cell ca's lung.
HER2/NEY (ERBB2)-amplified in 25-30% breast cancers-> bad prognosis.
rx: role of anti-HER2/NEU
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