neoplasm 4 Flashcards
define dysplasia
- disordered growth = loss in uniformity of individual cells and loss in their architectural orientation
- -> pleomorphism and mitoses are more prominent than in normal tissue
- Dysplasia may be a precursor to cancer, but does NOT invariable progress to cancer
describe the spectrum of squamous neoplasia of the cervix
- Grade of CIN is defined by proportion of the epithelium occupied by immature cells
- invasive carcinoma occurs when the abnormal cells invade through (“breach”) the basement membrane
- CIN 1 = 1/3 full thickness of immature cells (mild)
- CIN 2 = 2/3 full thickness (moderate)
- CIN 3 = 2/3-3/3 full thickness (severe)
- carcinoma in situ(CIS) = full thickness
define carcinoma in situ (CIS)
- full-thickness dysplasia extending from BM to surface of epithelium
- applicable only to epithelial neoplasm
what occurs if oral leukoplakia undergoes dysplasia
- squamous cell carcinoma
what occurs if barrett esophagus (metaplasia) undergoes dysplasia
- Adeocarcinoma of esophagus
what occurs if chonric atrophic gastritis of pernicious anemia undergoes dysplasia
- gastric adenocarcinoma
What occurs if chornic ulcerative colitis undergoes dysplasia
- adenocarcinoma of colon
what occurs if hepatitis infection (B or C) undergo cirrhosis
- macro-nodular cirrhosis develops and then hepato-cellular carcinoma
what occurs if simple/comlex hyperplasia occurs in endometrium
- simple/complex hyperplasia develops into atypical hyperplasia (endometrical intra-epithelial neoplasia (EIN))
- EIN develops into endometrial adenocarcinoma
what occurs if solar keratosis of skin undergoes dysplasia
- skin cancer (usually squamous cell carcinoma)
what are the essential alterations for malignant transformation (some are needed)
- self-sufficiency in growth signals
- insensitivity to growth-inhibitory signals
- evasion of apoptosis
- limitless replicative potential
- sustained angiogenesis
- ability to invade and metastasize
- defects in DNA repair
what are the 4 classes of normal regulatory genes
- growth promoting proto-oncogenes
- growth inhibiting tumor suppressor genes
- genes regulating apoptosis
- genes regulating DNA repair
define proto-oncogenes
- responsible for regulation of growth and differentiation
- once activated, proto-oncogene becomes oncogene
- activation mechanism: mutation, chromosomal translocation and amplification
- oncogene is the cancer causing gene
what mechanimism is involved in activation of oncogen
- chemical carcinogen, radiation, infectious agent causes DNA damage
- DNA damage leads to point mutation, translocation, amplification
- leads to transformation with genetic defect
- final effect is normal protein is overproduced or mutant protein is produced and has an aberrant function
define ERBB2 Receptor
- growth factor receptor (EGF)
- also known as (HER-2/NEU)
- causes amplification
- found in breast and ovarian cancer
define RET recetpor
- receptor for neurotropic factors (GH)
- causes point mutations
- found in MEN 2A and 2B, familial meduallary thyroid carcinomas
define KRAS receptor
- GTP-binding receptor
- causes point mutation in protein invovled in signal transduction
- found in pancreas, colon and lung cancers
define ABL receptor
- non-receptor tyrosine kinase
- causes translocation in proteins in signal transduction
- found in chronic myeloid leukemia and actue lymphoblastic leukemia
define B-catenin receptor
- WNT signal transduction recetpor
- causes point mutation and over-expression in protein involved in signal transduction
- found in hepato-blastomas and hepatocellular carcinoma (LIVER CANCER)
define BRAF
- RAS signal transduction
- causes point mutations in proteins involved in signal transduction
- found in melanomas
define C-myc receptor
- transcriptional activator
- causes translocation of nuclear-regulatory proteins
- found in burkitt lymphoma
define N-Myc receptor
- transcriptional activator
- casues amplification of nuclear-regulatory proteins
- found in neuroblastoma, small-cell carcinoma of the lung
define cyclin D
- causes translocation of cell cycle regulators = found in mantle cell lymphoma
- causes amplification of cell cycle regulators = found in breast and esophageal cancers
describe Multiple endocrine neoplasia types 2a and 2b
- caused by mutation of RET PROTO-ONCOGENE
- involves lots of organs
- -> thyroid, pancreas, parathyroid
- -> can be hyperplasia or tumor
describe chronic myelogenous leukemia (CML)
- c-abl proto-oncogene on chromosome 9 is translocated to bcr (an oncogene on chromosome 22)
- -> new chromosome referred to as philadelphia chromosome
- -> increases tyrosine kinase activity causing stimulation of proliferation of granulocytic precursors giving rise to chronic myeloid leukemia (CML)
describe imatinib mesylate
- INHIBITS tyrosine kinase and can be used to treat CML
describe burkitt lymphoma
- translocation of C-MYC proto-oncogene from chromosome 8 to a site adjacent to Ig heavy chain locus on chromosome 14
- leads to over-expression or amplification of C-MYC leads to excess transcription signals
describe B-cell follicular lymphoma
- BCL-2 genes produce gene products that PREVENT mitochondrial leakage of cytochrome C (signal for apoptosis)
- BCL-2 = anti-apoptotic factor
- Transolocation (14 to 18) leading to overexpression of BCL-2 protein product causing inhibition of apoptosis of B lymphocytes –> FOLLICULAR LYMPHOMA
- *PATHOGENESIS is EXCLUSIVELY BY EVASION OF APOPTOSIS**
Describe neuroblastoma
- amplification of N-MYC
- only 40% are associated with amplification of N-MYC
