Mismatch repair deficiency in canine neoplasms

被引:3
作者
Inanaga, Sakuya [1 ]
Igase, Masaya [1 ]
Sakai, Yusuke [1 ]
Tanabe, Mika [2 ]
Shimonohara, Nozomi [3 ]
Itamoto, Kazuhito [1 ]
Nakaichi, Munekazu [1 ]
Mizuno, Takuya [1 ]
机构
[1] Yamaguchi Univ, Yamaguchi, Japan
[2] Vet Pathol Diagnost Ctr, Fukuoka, Japan
[3] IDEXX Labs, Tokyo, Japan
关键词
dogs; hepatocellular carcinoma; immunohistochemistry; mismatch repair deficiency; neoplasia; oral malignant melanoma; PROTEIN EXPRESSION; PD-1; BLOCKADE; RESISTANCE; MUTATIONS; CELLS; MSH2; HETERODIMER; HOMOLOG; TUMORS;
D O I
10.1177/03009858211022704
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
The DNA mismatch repair (MMR) system preserves genomic stability by identifying and repairing mismatched nucleotides in the DNA replication process. The dysfunction of the MMR system, also known as mismatch repair deficiency (dMMR), is implicated as a predictive biomarker for the efficacy of immune checkpoint blockade therapy regardless of the tumor type in humans. This study aimed to evaluate the immunolabeling of MMR proteins in canine tumors and to identify the types of tumors having dMMR. First, we performed immunohistochemistry in 8 different canine tumors (oral malignant melanoma, high-to-intermediate grade lymphoma, mast cell tumor, malignant mammary gland tumor, urothelial carcinoma, hepatocellular carcinoma, osteosarcoma, and hemangiosarcoma) with 15 samples each to analyze the immunolabeling of canine mismatch repair proteins (MSH2, MSH6, and MLH1) using anti-human monoclonal antibodies. We found that more than half of canine oral malignant melanoma (60%) and hepatocellular carcinoma (53%) samples and fewer of the other canine tumors had loss of immunolabeling in >= 1 MMR protein (ie, evidence of defective MMR proteins, based on the definition of dMMR in the humans). Antibodies against human MSH2, MSH6, and MLH1 were cross-reactive with the corresponding canine protein as confirmed using MMR gene knockout canine cell lines. Further studies are required to investigate the clinical outcomes in canine spontaneous tumors with dMMR to determine the potential for immune checkpoint blockade therapy for these tumor types.
引用
收藏
页码:1058 / 1063
页数:6
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