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Evaluation of Micro Satellite Instability and Mismatch Repair Status in Different Solid Tumors: A Multicenter
Umberto Malapelle1, Paola Parente2, Francesco Pepe1
1Department of Public Health, University of Naples Federico II, 80131 Naples, Italy.
Abstract:
Immune-checkpoint inhibitors (ICIs) play a key role in the treatment of advanced stage colorectal cancer (CRC) patients featuring a deficient DNA mismatch repair (dMMR) system or a high microsatellite instability (MSI-H) profile. However, beyond the established role in CRC patients, ICIs have highly proven efficacy in other solid tumors featuring MSI-H/dMMR status represented by endometrial, gastric, ovarian, prostatic, and pancreatic carcinomas (EC, GC, OC, PrC, and PaC). Our aim was to compare the concordance rates among the Idylla™ MSI test, TapeStation 4200, and immunohistochemical (IHC) analysis in assessing MSI-H/dMMR status in EC, GC, OC, PrC, and PaC patients. The Sanger sequencing-based Titano MSI test was used in discordant cases. One hundred and eighty-five cases (n = 40 PrC, n = 39 GC, n = 38 OC, n = 35 PaC, and n = 33 EC) were retrospectively selected. MMR protein expression was evaluated by IHC. After DNA quality and quantity evaluations, the IdyllaTM and TapeStation 4200 platforms were adopted for the evaluation of MSI status. Remarkably, compared to IHC, the Idylla™ platform achieved a global concordance rate of 94.5% (154/163) for the microsatellite stable (MSS)/proficient MMR (pMMR) cases and 77.3% (17/22) for the MSI-H/dMMR cases. Similarly, a global concordance rate of 91.4% (149/163) and 68.2% (15/22) for MSS/pMMR and MSI-H/dMMR cases was also identified between IHC and the TapeStation 4200 microfluidic system. In addition, a global concordance of 93.1% (148/159) and 69.2% (18/26) for MSS/pMMR and MSI-H/dMMR cases was observed between the Idylla™ and TapeStation 4200 platforms. Discordant cases were analyzed using the Titano MSI kit. Overall, our data pinpointed a central role for molecular techniques in the diagnostic evaluation of dMMR/MSI-H status not only in CRC patients but also in other types of solid tumors.
Insights
Molecular tests like Idylla™ and TapeStation 4200 accurately assess microsatellite instability-high (MSI-H)/deficient DNA mismatch repair (dMMR) status in various cancers. These methods are crucial for guiding immune-checkpoint inhibitor (ICI) therapy beyond colorectal cancer.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- Immune-checkpoint inhibitors (ICIs) are effective for advanced colorectal cancer (CRC) with MSI-H/dMMR status.
- ICIs also show efficacy in other solid tumors with MSI-H/dMMR, including endometrial, gastric, ovarian, prostatic, and pancreatic carcinomas.
- Accurate assessment of MSI-H/dMMR status is critical for patient selection for ICI therapy across tumor types.
Purpose of the Study:
- To compare the concordance rates of Idylla™ MSI test, TapeStation 4200, and immunohistochemistry (IHC) for MSI-H/dMMR assessment.
- To evaluate the utility of these molecular techniques in endometrial, gastric, ovarian, prostatic, and pancreatic carcinomas.
- To analyze discordant cases using Sanger sequencing-based Titano MSI test.
Main Methods:
- Retrospective analysis of 185 solid tumor cases (endometrial, gastric, ovarian, prostatic, pancreatic carcinomas).
- Evaluation of MMR protein expression by immunohistochemistry (IHC).
- Assessment of MSI status using Idylla™ MSI test and TapeStation 4200 platform.
- Analysis of discordant cases with the Titano MSI kit.
Main Results:
- Idylla™ showed high concordance with IHC for microsatellite stable (MSS)/proficient MMR (pMMR) cases (94.5%) and moderate concordance for MSI-H/dMMR cases (77.3%).
- TapeStation 4200 also demonstrated good concordance with IHC for MSS/pMMR (91.4%) and lower concordance for MSI-H/dMMR (68.2%).
- Concordance between Idylla™ and TapeStation 4200 was also high for MSS/pMMR (93.1%) and moderate for MSI-H/dMMR (69.2%).
Conclusions:
- Molecular techniques like Idylla™ and TapeStation 4200 are valuable for assessing MSI-H/dMMR status in various solid tumors.
- These methods play a crucial role in diagnostic evaluation, extending beyond CRC to other cancer types.
- Molecular testing is essential for identifying patients who may benefit from immune-checkpoint inhibitor therapy.
