http://hdl.handle.net/1765/9905

Microsatellite instability of germ cell tumors is associated with resistance to systemic treatment


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Systemic cisplatin-based chemotherapy cures > or =90% of patients with metastatic germ cell tumors (GCTs). The biological basis of this exquisite chemo-sensitivity and the resistant phenotype encountered in 10-15% of patients with GCT is yet unclear. A defective mismatch repair pathway leading to microsatellite instability (MSI) has been related to resistance to cytotoxic drugs. We investigated 100 unselected GCTs and 11 clinically defined chemotherapy-resistant GCTs for MSI using 8 mono- or dinucleotide markers and the presence of the mismatch repair factors MLH1, MSH2, and MSH6 by immunohistochemistry. The resistant tumors, both chemo-naive (n = 8) and pretreated (n = 3), showed a significantly higher incidence of MSI compared with the unselected series (45 versus 6% in at least one locus and 36 versus 0% in > or =2 of 8 loci, both P < or = 0.001). In 5 of all 11 unstable tumors, MSI correlated with immunohistochemical findings. This study demonstrates for the first time a positive correlation between MSI and treatment resistance in GCT.



Keywords


Automatically Extracted Terms
  • tumor
  • cancer
  • microsatellite instability
  • microsatellite
  • instability
  • resistance
  • germ cell tumors
  • treatment
  • patient
  • chemotherapy
  • msh 6
  • analysis
  • survival
  • mmr factors
  • difference
  • unselected
  • series
  • nonseminoma
  • mismatch
  • dna mismatch repair


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