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[Cancer Research 62, 2758-2760, May 15, 2002]
© 2002 American Association for Cancer Research

Advances in Brief

Microsatellite Instability of Germ Cell Tumors Is Associated with Resistance to Systemic Treatment1

Frank Mayer, Ad J. M. Gillis, Winand Dinjens, J. Wolter Oosterhuis, Carsten Bokemeyer and Leendert H. J. Looijenga2

Pathology/Laboratory for Exp. Patho-Oncology [F. M., A. J. M. G., J. W. O., L. H. J. L.] and Pathology/Molecular Diagnostics [W. D.], University Hospital Rotterdam/Daniel, Josephine Nefkens Institute, 3000 DR Rotterdam, the Netherlands, and Department of Oncology, Hematology, Immunology, and Rheumatology, University of Tuebingen Medical Center, Tuebingen 72076, Germany [F. M., C. B.]

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.




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