Open AccessExploring microsatellite instability in patients with advanced hepatocellular carcinoma and its tumor microenvironment
Author(s) -
Mukai Shohei,
Kanzaki Hiroaki,
Ogasawara Sadahisa,
Ishino Takamasa,
Ogawa Keita,
Nakagawa Miyuki,
Fujiwara Kisako,
Unozawa Hidemi,
Iwanaga Terunao,
Sakuma Takafumi,
Fujita Naoto,
Koroki Keisuke,
Kobayashi Kazufumi,
Kanogawa Naoya,
Kiyono Soichiro,
Nakamura Masato,
Kondo Takayuki,
Saito Tomoko,
Nakagawa Ryo,
Suzuki Eiichiro,
Ooka Yoshihiko,
Muroyama Ryosuke,
Nakamoto Shingo,
Tawada Akinobu,
Chiba Tetsuhiro,
Arai Makoto,
Kato Jun,
Shiina Manayu,
Ota Masayuki,
Ikeda Junichiro,
Takiguchi Yuichi,
Ohtsuka Masayuki,
Kato Naoya
Publication year - 2021
Publication title -
jgh open
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.546
H-Index - 8
ISSN - 2397-9070
DOI - 10.1002/jgh3.12660
Subject(s) - microsatellite instability , msh2 , pembrolizumab , tumor microenvironment , hepatocellular carcinoma , dna mismatch repair , tumor infiltrating lymphocytes , cancer research , medicine , mlh1 , liver cancer , oncology , colorectal cancer , cancer , biology , immunotherapy , gene , microsatellite , biochemistry , allele
Background and Aim Immune checkpoint inhibitors and their combination with other agents have recently been available in advanced hepatocellular carcinoma (HCC). Hence, a thorough understanding of the tumor microenvironment based on tumor samples is yet to be achieved. This study aimed to explore the tumor microenvironment in advanced HCC in terms of microsatellite instability‐high (MSI‐H) by using tumor samples from advanced HCC patients eligible for systemic therapy. Methods MSI‐H was assessed by polymerase chain reaction, and the expression of mismatch repair proteins, PD‐L1, CD8, VEGF, and HLA‐class1 was evaluated by immunohistochemistry. Whole‐exome sequencing was performed for MSI‐H tumor samples. Results Of 50 patients, one (2.0%) was confirmed with MSI‐H. In the MSI‐H advanced HCC tumor, a high tumor mutation burden, infiltration of CD8 + lymphocytes, and low expression of VEGF were identified. Although PD‐L1 expression was negative, there was shrinkage of tumor following pembrolizumab. However, another tumor nonresponsive to pembrolizumab was present simultaneously. Checking the Cancer Genome Atlas (TCGA) database, we found a similar case to this patient. The TCGA case had unique gene features of miR‐21 and miR‐155 overexpression and hypermethylation of the MSH2 gene. Conclusion We identified a very small number of MSI‐H cases in HCC using one tumor biopsy sample for each patient with advanced HCC. In addition, epigenetic aberrations possibly lead to MSI‐H in HCC patients. Since different HCC clones might coexist in the liver, sampling from multiple tumors should be considered to clarify the true proportion of MSI‐H in HCC and to analyze tumor microenvironments.