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

Frank Mayer, Ad J M Gillis, Winand Dinjens, J Wolter Oosterhuis, Carsten Bokemeyer, Leendert H J Looijenga

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

Samenvatting

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-naïve (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.

Originele taal-2Engels
Pagina's (van-tot)2758-60
Aantal pagina's3
TijdschriftCancer Research
Volume62
Nummer van het tijdschrift10
StatusGepubliceerd - 15 mei 2002
Extern gepubliceerdJa

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