PT  - JOURNAL ARTICLE
AU  - Mayer, Frank
AU  - Gillis, Ad J. M.
AU  - Dinjens, Winand
AU  - Oosterhuis, J. Wolter
AU  - Bokemeyer, Carsten
AU  - Looijenga, Leendert H. J.
TI  - Microsatellite Instability of Germ Cell Tumors Is Associated with Resistance to Systemic Treatment
DP  - 2002 May 15
TA  - Cancer Research
PG  - 2758--2760
VI  - 62
IP  - 10
4099  - http://cancerres.aacrjournals.org/content/62/10/2758.short
4100  - http://cancerres.aacrjournals.org/content/62/10/2758.full
SO  - Cancer Res2002 May 15; 62
AB  - Systemic cisplatin-based chemotherapy cures ≥90% of patients with metastatic germ celltumors (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 ≥2 of 8 loci, both P ≤ 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. ©2002 American Association for Cancer Research.