Rare DNA Mismatch Repair-Related Protein Loss in Patients with Intrahepatic Cholangiocarcinoma and Combined Hepatocellular-Cholangiocarcinoma and Their Response to Immunotherapy

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...

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Main Authors: Yu J, Zhang X, Huang Q, Tan S, Xiong X, Gou H
Format: Article
Language:English
Published: Dove Medical Press 2021-05-01
Series:Cancer Management and Research
Subjects:
Online Access:https://www.dovepress.com/rare-dna-mismatch-repair-related-protein-loss-in-patients-with-intrahe-peer-reviewed-fulltext-article-CMAR
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author Yu J
Zhang X
Huang Q
Tan S
Xiong X
Gou H
author_facet Yu J
Zhang X
Huang Q
Tan S
Xiong X
Gou H
author_sort Yu J
collection DOAJ
description 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 gouhongfeng1977@wchscu.cnXianze XiongDepartment of Bile Duct Surgery, West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, 610041, Sichuan Province, People’s Republic of ChinaEmail xianzexiong123@163.comPurpose: 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
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spelling doaj.art-96b37ec71e5940adbe8272837456e9482022-12-21T22:45:53ZengDove Medical PressCancer Management and Research1179-13222021-05-01Volume 134283429065318Rare DNA Mismatch Repair-Related Protein Loss in Patients with Intrahepatic Cholangiocarcinoma and Combined Hepatocellular-Cholangiocarcinoma and Their Response to ImmunotherapyYu JZhang XHuang QTan SXiong XGou HJing 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 gouhongfeng1977@wchscu.cnXianze XiongDepartment of Bile Duct Surgery, West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, 610041, Sichuan Province, People’s Republic of ChinaEmail xianzexiong123@163.comPurpose: 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, prognosishttps://www.dovepress.com/rare-dna-mismatch-repair-related-protein-loss-in-patients-with-intrahe-peer-reviewed-fulltext-article-CMARmismatch-repair deficiencyintrahepatic cholangiocarcinomacombined hepatocellular-cholangiocarcinomaimmune checkpoint inhibitorsprognosis
spellingShingle Yu J
Zhang X
Huang Q
Tan S
Xiong X
Gou H
Rare DNA Mismatch Repair-Related Protein Loss in Patients with Intrahepatic Cholangiocarcinoma and Combined Hepatocellular-Cholangiocarcinoma and Their Response to Immunotherapy
Cancer Management and Research
mismatch-repair deficiency
intrahepatic cholangiocarcinoma
combined hepatocellular-cholangiocarcinoma
immune checkpoint inhibitors
prognosis
title Rare DNA Mismatch Repair-Related Protein Loss in Patients with Intrahepatic Cholangiocarcinoma and Combined Hepatocellular-Cholangiocarcinoma and Their Response to Immunotherapy
title_full Rare DNA Mismatch Repair-Related Protein Loss in Patients with Intrahepatic Cholangiocarcinoma and Combined Hepatocellular-Cholangiocarcinoma and Their Response to Immunotherapy
title_fullStr Rare DNA Mismatch Repair-Related Protein Loss in Patients with Intrahepatic Cholangiocarcinoma and Combined Hepatocellular-Cholangiocarcinoma and Their Response to Immunotherapy
title_full_unstemmed Rare DNA Mismatch Repair-Related Protein Loss in Patients with Intrahepatic Cholangiocarcinoma and Combined Hepatocellular-Cholangiocarcinoma and Their Response to Immunotherapy
title_short Rare DNA Mismatch Repair-Related Protein Loss in Patients with Intrahepatic Cholangiocarcinoma and Combined Hepatocellular-Cholangiocarcinoma and Their Response to Immunotherapy
title_sort rare dna mismatch repair related protein loss in patients with intrahepatic cholangiocarcinoma and combined hepatocellular cholangiocarcinoma and their response to immunotherapy
topic mismatch-repair deficiency
intrahepatic cholangiocarcinoma
combined hepatocellular-cholangiocarcinoma
immune checkpoint inhibitors
prognosis
url https://www.dovepress.com/rare-dna-mismatch-repair-related-protein-loss-in-patients-with-intrahe-peer-reviewed-fulltext-article-CMAR
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