Aydın AH, Turhan N. Comparison of mismatch repair and immune checkpoint protein profile with histopathological parameters in pancreatic, periampullary/ampullary, and choledochal adenocarcinomas. World J Gastrointest Oncol 2024; 16(3): 875-882 [PMID: 38577456 DOI: 10.4251/wjgo.v16.i3.875]
Corresponding Author of This Article
Arzu Hazal Aydın, MD, Doctor, Department of Pathology, Aksaray University Aksaray Training and Research Hospital, Sifahane District, No. 3152 Street, Aksaray 68200, Turkey. arzu.hazal.aydin@gmail.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Retrospective Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Oncol. Mar 15, 2024; 16(3): 875-882 Published online Mar 15, 2024. doi: 10.4251/wjgo.v16.i3.875
Comparison of mismatch repair and immune checkpoint protein profile with histopathological parameters in pancreatic, periampullary/ampullary, and choledochal adenocarcinomas
Arzu Hazal Aydın, Nesrin Turhan
Arzu Hazal Aydın, Department of Pathology, Aksaray University Aksaray Training and Research Hospital, Aksaray 68200, Turkey
Nesrin Turhan, Department of Pathology, University of Health Sciences Ankara City Hospital, Ankara 06800, Turkey
Author contributions: Aydın AH and Turhan N participated in the design, execution, and analysis of the article and approved the final version.
Institutional review board statement: Prior to the study, approval was obtained from T.C. Health Sciences University Ankara City Hospital Ethics Committee (Numbered E2-2021-601; Dated 16/06/2021).
Informed consent statement: Since the study was retrospectively designed, informed consent was not obtained from the patients.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Arzu Hazal Aydın, MD, Doctor, Department of Pathology, Aksaray University Aksaray Training and Research Hospital, Sifahane District, No. 3152 Street, Aksaray 68200, Turkey. arzu.hazal.aydin@gmail.com
Received: November 3, 2023 Peer-review started: November 3, 2023 First decision: December 1, 2023 Revised: December 12, 2023 Accepted: January 10, 2024 Article in press: January 10, 2024 Published online: March 15, 2024 Processing time: 129 Days and 20.4 Hours
Abstract
BACKGROUND
Pancreatic, periampullary/ampullary, and choledochal adenocarcinomas are aggressive malignancies with a poor prognosis. Immune checkpoint blockade is a promising treatment option for several tumor types. H long terminal repeat-associating 2 (HHLA2), which is analogous to programmed death-ligand 1 (PD-L1), is a recently discovered member of the B7/cluster of differentiation 28 family and is expressed in many malignancies.
AIM
To analyze the expression of HHLA2 and its association with the pathologic biomarkers that predict sensitivity to immunotherapy.
METHODS
Ninety-two adenocarcinoma cases located in the pancreas, ampulla, and distal common bile duct were identified. This study assessed 106 pancreaticoduodenectomy and distal/total pancreatectomy samples that were delivered to Ankara City Hospital between 2019 and 2021. Immunohistochemistry was conducted to examine the expression of DNA mismatch repair (MMR), PD-L1, and HHLA2 proteins.
RESULTS
Patients with high HHLA2 expression had a higher mean age than those with low expression. Low HHLA2 expression was associated with high perineural invasion. HHLA2 expression was low in pathological stage T3 (pT) 3 cases and high in pathological stage T1, T2, and T4 cases. There was no correlation between HHLA2 expression and the expression of MMR proteins and PD-L1.
CONCLUSION
Evaluation of HHLA2 expression in microsatellite stable and PD-L1-negative tumors may be useful for predicting the response of individuals to immunotherapy and may serve as a novel therapeutic target for immunotherapy in advanced-stage disease.
Core Tip: Pancreatic, periampullary/ampullary, and choledochal adenocarcinomas are aggressive malignancies with recurrences and metastases occurring in a short period of time. Complete resection is possible in only a small proportion of patients; thus, targeted therapies are needed. H long terminal repeat-associating 2 (HHLA2), which is analogous to programmed death-ligand 1 (PD-L1), is expressed in many malignancies. Evaluation of HHLA2 expression in microsatellite stable and PD-L1-negative tumors may be useful for predicting the response of individuals to immunotherapy, and may serve as a novel therapeutic target in patients with advanced disease who do not respond to classical chemotherapy and have unresectable cancer.
