A pilot study on the detection of microsatellite instability using long mononucleotide repeats in solid tumors

Liu,Tsunglin; Ho,Chung-Liang; Chen,Yan-Jhen; Chen,Pin-Jun; Chen,Wan-Li; Lee,Chung-Ta; Chow,Nan-Haw; Huang,Wenya; Chen,Yi-Lin

doi:10.3892/ol.2024.14578

A pilot study on the detection of microsatellite instability using long mononucleotide repeats in solid tumors

Authors:
- Tsunglin Liu
- Chung-Liang Ho
- Yan-Jhen Chen
- Pin-Jun Chen
- Wan-Li Chen
- Chung-Ta Lee
- Nan-Haw Chow
- Wenya Huang
- Yi-Lin Chen
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Affiliations: Department of Biotechnology and Bioindustry Sciences, National Cheng Kung University, Tainan 701, Taiwan, R.O.C., Molecular Diagnosis Laboratory, Department of Pathology, National Cheng Kung University Hospital, Tainan 704, Taiwan, R.O.C., Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan, R.O.C., Department of Laboratory Medicine, Center for Precision Medicine, China Medical University Hospital, Taichung 404, Taiwan, R.O.C.
Published online on: July 22, 2024 https://doi.org/10.3892/ol.2024.14578
Article Number: 445
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Microsatellite instability (MSI) status is a prognostic biomarker for immunotherapy in certain types of cancers, such as colorectal cancers (CRCs) and endometrial cancers (ECs). Tumors that are categorized as having high MSI (MSI‑H) express high levels of neoantigens for immune recognition. The typical MSI test measures the length of short mononucleotide repeats (SMR) poly(A) 21‑27; however, a limitation of this test is the difficulty in determining the shift size, particularly in endometrial cancer. To investigate an MSI detection assay with improved performance, the present study analyzed the use of poly(A) 40‑44 mononucleotide repeats to detect the MSI status of 100 patients with either CRC (n=50) or EC (n=50). Capillary electrophoresis was used to evaluate five long mononucleotide repeat (LMR) markers, including poly(A) 40‑A, 40‑B, 40‑C, 40‑D and 44. The concordance rate of the LMR‑MSI assay compared with an immunohistochemistry MSI detection assay was 96.0 and 95.1% for CRCs and ECs respectively, with the detection limit of the LMR‑MSI assay demonstrated to be 2.5% MSI‑H in HCT116 colorectal carcinoma cell lines. The LMR‑MSI assay yielded a 95.1% concordance rate in ECs compared with that in the SMR‑MSI test (87.8%). The LMR‑MSI test identified a significantly higher mean shift size (13 bp) in MSI‑H tumors compared with the SMR‑MSI test (10 bp), in both EC and CRC tissue samples. Together, the present study suggested that the LMR‑MSI test could potentially be a sensitive and practical technology for molecular laboratory testing, particularly in the use of immunotherapy for patients with CRCs and ECs.

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