Evaluation of Micro Satellite Instability and Mismatch Repair Status in Different Solid Tumors: A Multicenter Analysis in a Real World Setting

作者：Umberto Malapelle, Paola Parente, Francesco Pepe, Caterina De Luca, Pasquale Pisapia, Roberta Sgariglia, Mariantonia Nacchio, Gianluca Gragnano, Gianluca Russo, Floriana Conticelli, Claudio Bellevicine, Elena Vigliar, Antonino Iaccarino, Claudia Covelli, Mariangela Balistreri, Celeste Clemente, Giovanni Perrone, Angela Danza, Fabio Scaramuzzi, Matteo Fassan, Giancarlo Troncone, Paolo Graziano · 发表于：Cells · 年份：2021 · DOI：10.3390/cells10081878 · 被引用次数：58 · 研究领域：Genetic factors in colorectal cancer、Colorectal Cancer Treatments and Studies、Cancer Genomics and Diagnostics

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% (...