AUTHOR=Xu Yanjie , Li Qin , Zhao Jiemin , Ni Xuefeng , Li Ping , Hu Wenwei 

TITLE=Case report: Complete response to pembrolizumab in a liver metastatic colon adenocarcinoma patient with a novel likely pathogenic germline MSH2 mutation

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1064488

DOI=10.3389/fimmu.2022.1064488

ISSN=1664-3224

ABSTRACT=<p>Lynch syndrome (LS) is a genetic disorder mainly caused by germline mutations in mismatched repair (MMR) genes (<italic>MSH2</italic>, <italic>MLH1</italic>, <italic>MSH6</italic>, and <italic>PMS2</italic>) or deletions of the epithelial cell adhesion molecule gene (<italic>EPCAM</italic>). A 43-year-old Chinese male patient underwent radical surgery and was pathologically confirmed to have stage IIIB colon adenocarcinoma. After four cycles of standard adjuvant chemotherapy, the tumor reoccurred <italic>in situ</italic> with intestinal obstruction. The patient received secondary colectomy. Immunohistochemistry analysis revealed a loss of MSH2 protein expression in the surgical specimen. Noticing that the patient’s mother and grandfather all were diagnosed with LS-related cancers, we collected the patient’s and his mother’s peripheral blood for genetic testing, and the result showed a six-base deletion of <italic>MSH2</italic>. Thus, we concluded that our patient had LS. Subsequently, the patient accepted pembrolizumab as the first-line systemic therapy after liver metastases. He achieved clinical complete response (cCR) within 2 months and remained progression-free for more than 2 years. The case report showed that <italic>MSH2</italic> mutation (c.489_494deTGGGTA) is a likely pathogenic mutation, and immunotherapy (pembrolizumab) is effective for this patient.</p>