Corresponding author: Yoshiyuki Takahashi, M.D., Ph.D.
65 Tsurumai-cho, Showa-ku
Nagoya 466-8550, Japan
Phone: +81-52-744-2294
Fax: +81-52-744-2974
E-mail: ytakaha@med.nagoya-u.ac.jp
Microsatellites are a set of repeating base sequences of one to several
bases in a chromosome. In general, mismatch repair (MMR) proteins
correct the base mismatches that occur during DNA replication. However,
tumor cells with deficient MMR function accumulate genetic mutations and
cause changes in the repeat counts in microsatellite sites, and such a
status is referred to as microsatellite instability (MSI)-high status.
According to recent research, MSI-high status is associated with
responsiveness to therapies with immune checkpoint inhibitors [1].
MSI status has been well described in various adult solid tumors; for
instance, one of the largest studies has demonstrated that 1188 (9.9%)
of 12,019 patients exhibited an MSI-high signature in various types of
tumors [2]. However, there are no sufficient investigations on the
MSI status in pediatric solid tumors, except those on limited tumor
subtypes, including glioblastoma and medulloblastoma [3, 4]. Herein,
we investigated the MSI status in pediatric patients with various solid
tumors who died due to the tumor and also evaluated the potential of
immune checkpoint inhibitors in refractory pediatric solid tumors.
From April 2000 to May 2019, a total of 334 pediatric patients with
solid tumors were admitted to the Nagoya University Hospital
(Table 1 ). Although the majority of patients survived, 74
(22%) died, including 68 due to relapse or refractory tumor, 4 due to
pulmonary complications after stem cell transplantations, and 2 due to
infection after chemotherapies. We retrospectively analyzed the
formalin-fixed paraffin-embedded tumor tissues of 40 (54%) of the 74
patients who died to assess the MSI status (Supplemental Table
1 , Supplemental Figure 1 ) using five multiplexed markers for
determining the MSI-high phenotype (BAT-25, BAT-26, MONO-27, NR-21, and
NR-24) (Supplemental methods ). Results demonstrated that 36
cases were microsatellite-stable and none of the patients had an
MSI-high status; however, this observation could not be confirmed for
the remaining four patients because of poor sample quality.
These results indicate that MSI-high status is rare in pediatric
patients with solid tumors who die of the disease. Therefore,
surveillance of MSI status in children with refractory/relapsed solid
tumors might have a limited role in predicting the responsiveness to
immune checkpoint inhibitors.