Abstract
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.
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 Supported by the Dutch Cancer Society/KWF (A. J. M. G., J. W. O., and L. H. J. L.). Frank Mayer was financially supported by the fellowship program of the European Society of Medical Oncology (ESMO).
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↵2 To whom requests for reprints should be addressed, at Pathology/Lab. for Exp. Patho-Oncology, University Hospital Rotterdam/Daniel, Josephine Nefkens Institute, Erasmus University Rotterdam, Building Be, room 430b, P. O. Box 1738, 3000 DR Rotterdam, the Netherlands. Phone: (31) 104088329; Fax: (31) 104088365; E-mail: Looijenga{at}leph.azr.n
- Received February 12, 2002.
- Accepted March 22, 2002.
- ©2002 American Association for Cancer Research.
Volume 62, Issue 10
