Cancer Management and Research (May 2021)
Rare DNA Mismatch Repair-Related Protein Loss in Patients with Intrahepatic Cholangiocarcinoma and Combined Hepatocellular-Cholangiocarcinoma and Their Response to Immunotherapy
Abstract
Jing Yu,1,* Xi Zhang,1,2,* Qiyue Huang,1 Sirui Tan,1 Xianze Xiong,3 Hongfeng Gou1 1Department of Abdominal Cancer, West China Medical School, Cancer Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Radiotherapy, The Affiliated Hospital of Hebei University, Baoding, 07100, People’s Republic of China; 3Department of Bile Duct Surgery, West China Hospital, Sichuan University, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongfeng GouDepartment of Abdominal Cancer, West China Medical School, Cancer Center, West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, 610041, Sichuan Province, People’s Republic of ChinaTel +86-28-85422589Fax +86-28-85423609Email [email protected] XiongDepartment of Bile Duct Surgery, West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, 610041, Sichuan Province, People’s Republic of ChinaEmail [email protected]: The patients with advanced mismatch repair deficiency (dMMR) cancers can benefit from programmed cell death 1 (PD-1) pathway blockade, regardless of the tumor type. Little is known about the prevalence of dMMR in intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular-cholangiocarcinoma (cHCC-CC). This study aimed to assess the mismatch repair (MMR)-related protein expression in patients with ICC and cHCC-CC.Patients and Methods: Formalin-fixed, paraffin-embedded tumor specimens were obtained from patients undergoing surgery at the West china Hospital between 2009 and 2017. The immunoreactions for MLH1, MSH2, MSH6, and PMS2 were investigated to determine the MMR status.Results: A total of 97 patients were evaluated, including 73 ICC patients and 24 cHCC-CC patients. The prevalence of dMMR was only found in two cases of 97 patients (2.06%). Both patients are ICC. In 24 cHCC-CC patients, no dMMR was observed. They did not receive an adjuvant chemotherapy after surgery. At the end of the follow-up, one patient was in a tumor-free state, and the other patient had local recurrence and metastasis. After receiving sintilimumab (an immune checkpoint inhibitor [ICI] for PD- 1), the patient had a partial response.Conclusion: DMMR was detected in few patients with ICC and cHCC-CC. Thus, it is not recommended to routinely evaluate the MMR status of patients with ICC or cHCC-CC after surgery, but that of patients with advanced ICC or cHCC-CC should be assessed.Keywords: mismatch-repair deficiency, intrahepatic cholangiocarcinoma, combined hepatocellular-cholangiocarcinoma, immune checkpoint inhibitors, prognosis
