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Analysis of microsatellite instability (MSI) in pediatric gonadal and extra-gonadal germ cell tumors
Marco Montella1, Maria Elena Errico2, Andrea Ronchi1
1Pathology Unit, Department of Mental Health and Physic and Preventive Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.
Abstract:
Gonadal and extragonadal pediatric germ cell tumors (GCTs) are rare neoplasms with different clinical behavior. Although surgery and cisplatin-based chemotherapy are resolutive in most cases, some patients do not respond to chemotherapy and have a worse outcome. Microsatellite instability (MSI) was correlated to resistance to chemotherapy and sensitivity to immunotherapy in different neoplasms. A series of 21 pediatric GCTs were tested by immuno-histochemistry and PCR to evaluate MSI status. Next generation sequencing was applied to further evaluate cases with discordant results between immunohistochemistry and PCR. Twenty-one cases of pediatric GCT were included in the series. The mean age ranged between 1 and 10 years. Nine cases were gonadal GCTs and the remaining 12 were extra-gonadal GCTs. By immunohistochemistry, one case showed a deficit of Mismatch repair (MMR) proteins. This case was a 1-year-old children affected by gonadal yolk sac tumor. However, all cases resulted microsatellite stable (MSS) by PCR and NGS. MSI was not detected in our series of pediatric GCTs, as well as the data present in literature about adult patients with GCTs. Molecular techniques could have a role to confirm the MSI status in case of dMMR by immunohistochemistry.
Insights
Pediatric germ cell tumors (GCTs) rarely exhibit microsatellite instability (MSI). This study found no MSI in 21 pediatric GCT cases, suggesting MSI is not a factor in treatment resistance for these rare cancers.
Area of Science:
- Oncology
- Molecular Pathology
- Pediatric Cancer Research
Background:
- Pediatric germ cell tumors (GCTs) are rare, with varied clinical behaviors.
- While surgery and chemotherapy are effective, some patients exhibit resistance, leading to poorer outcomes.
- Microsatellite instability (MSI) is linked to chemotherapy resistance and immunotherapy sensitivity in other cancers.
Purpose of the Study:
- To investigate the prevalence and significance of microsatellite instability (MSI) in pediatric GCTs.
- To determine if MSI status correlates with treatment response or clinical behavior in pediatric GCTs.
- To evaluate the utility of molecular techniques in assessing MSI in pediatric GCTs.
Main Methods:
- Analysis of 21 pediatric GCT cases (gonadal and extragonadal).
- Assessment of MSI status using immunohistochemistry (IHC) for mismatch repair (MMR) proteins and polymerase chain reaction (PCR).
- Next-generation sequencing (NGS) employed for cases with discordant IHC and PCR results.
Main Results:
- One case of gonadal yolk sac tumor in a 1-year-old showed a deficit in MMR proteins via IHC.
- All 21 pediatric GCT cases were confirmed as microsatellite stable (MSS) by PCR and NGS.
- No evidence of MSI was detected in this pediatric GCT cohort or in existing literature on adult GCTs.
Conclusions:
- Microsatellite instability (MSI) is not detected in pediatric germ cell tumors (GCTs).
- The findings suggest MSI is not a predictive biomarker for chemotherapy resistance in pediatric GCTs.
- Molecular techniques can aid in confirming MSI status when IHC suggests mismatch repair deficiency.
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