etiology and pathogenesis of cancer - lecture - julia

Question 1

how would pancreatic cancer change histologically over time? what is the expected time course for these changes?

Answer 1

• 1-2 months - have focal hyperplasia - mostly normal pancreatic tissue but a small mass of abnormal cells with large nuclei, chromatin
• 4-6 months - this spreads to become multiple hyperplastic nodules
• by 6-12 months, it’s an adenoma - still benign cause confined to basement membrane - cells smaller and packed densely in comparison with normal cells - overall enlargement of previous hyperplastic nodule
• 1-2 years - acinar cell carcinoma - irregular nuclei, clumped chromatin, some atypical mitosis, too much mitosis in general (usually wouldn’t see mitosis at all in pancreatic tissue)

Question 2

what are two enabling characteristics that are crucial for carcinogenesis?

Answer 2

1. genome instability (destabilization of gene copy number and nucleotide sequence)
2. tumor promoting inflammation leading to release of growth factors, survival factors, proangiogenic factors, reactive O2 species (mutagenic)

Question 3

what can cause genome instability? (2)

Answer 3

1. increased sensitivity to mutagenic agents
2. breakdown in caretaker genes which control various components of DNA-maintenance machinery such as:
   - detection of DNA damage
   - repair of damaged DNA
   - inactivation of mutagenic molecules
   - telomere maintenance