학술논문
Genomic Profiling of Rare Undifferentiated Sarcomatoid Subtypes of Pancreatic Carcinomas: In Search of Therapeutic Targets.
Document Type
Academic Journal
Author
Faber EB; Medical Scientist Training Program, University of Minnesota Medical School, Minneapolis, MN.; Krause HB; Caris Life Sciences, Dallas, TX.; Amin K; Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN.; Walker P; Caris Life Sciences, Dallas, TX.; Hosein PJ; Sylvester Comprehensive Cancer Center, University of Miam, Miami, FL.; Shields AF; Karmanos Cancer Institute, Wayne State University, Detroit, MI.; Lenz HJ; Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.; Prakash A; Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, MN.; Goel S; Rutgers Cancer Institute of NJ, New Brunswick, NJ.; Oberley M; Caris Life Sciences, Dallas, TX.; Malleo G; Department of Surgery, Dentistry, Pediatrics and Gynecology, Unit of General and Pancreatic Surgery, University and Hospital Trust of Verona, Verona, Italy.; Luchini C; Department of Diagnostics and Public Health, Section of Pathology, and ARC-Net Research Center, University and Hospital Trust of Verona, Verona, Italy.; Hwang J; Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, MN.; Florou V; University of Utah Huntsman Cancer Institute, Salt Lake City, UT.; Garrido-Laguna I; University of Utah Huntsman Cancer Institute, Salt Lake City, UT.; Lou E; Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, MN.
Source
Publisher: American Society of Clinical Oncology Country of Publication: United States NLM ID: 101705370 Publication Model: Print Cited Medium: Internet ISSN: 2473-4284 (Electronic) Linking ISSN: 24734284 NLM ISO Abbreviation: JCO Precis Oncol Subsets: MEDLINE
Subject
Language
English
Abstract
Purpose: The highly aggressive undifferentiated sarcomatoid carcinoma (USC) subtype of pancreatic ductal adenocarcinoma (PDAC) remains poorly characterized because of its rarity. Previous case reports suggest that immune checkpoint inhibitors could be a promising treatment strategy, but the prevalence of established predictive biomarkers of response is largely unknown. The objective of this study was to leverage comprehensive genomic profiling of USC PDAC tumors to determine the prevalence of biomarkers associated with potential response to targeted therapies.
Methods: USC tumors (n = 20) underwent central pathology review by a board-certified gastrointestinal pathologist to confirm the diagnosis. These samples were compared with non-USC PDAC tumors (N = 5,562). Retrospective analysis of DNA and RNA next-generation sequencing data was performed.
Results: USC PDACs were more frequently PD-L1+ by immunohistochemistry than non-USC PDAC (63% v 16%, respectively, P < .001). Furthermore, USC PDAC had an increase in neutrophils (8.99% v 5.55%, P = .005) and dendritic cells (1.08% v 0.00%, q = 0.022) and an increased expression of PDCD1LG2 (4.6% v 1.3%, q = 0.001), PDCD1 (2.0% v 0.8%, q = 0.060), and HAVCR2 (45.9% v 21.7%, q = 0.107) than non-USC PDAC. Similar to non-USC PDAC, KRAS was the most commonly mutated gene (86% v 90%, respectively, P = 1).
Conclusion: To our knowledge, this work represents the largest molecular analysis of USC tumors to date and showed an increased expression of immune checkpoint genes in USC tumors. These findings provide evidence for further investigation into immune checkpoint inhibitors in USC tumors.
Methods: USC tumors (n = 20) underwent central pathology review by a board-certified gastrointestinal pathologist to confirm the diagnosis. These samples were compared with non-USC PDAC tumors (N = 5,562). Retrospective analysis of DNA and RNA next-generation sequencing data was performed.
Results: USC PDACs were more frequently PD-L1+ by immunohistochemistry than non-USC PDAC (63% v 16%, respectively, P < .001). Furthermore, USC PDAC had an increase in neutrophils (8.99% v 5.55%, P = .005) and dendritic cells (1.08% v 0.00%, q = 0.022) and an increased expression of PDCD1LG2 (4.6% v 1.3%, q = 0.001), PDCD1 (2.0% v 0.8%, q = 0.060), and HAVCR2 (45.9% v 21.7%, q = 0.107) than non-USC PDAC. Similar to non-USC PDAC, KRAS was the most commonly mutated gene (86% v 90%, respectively, P = 1).
Conclusion: To our knowledge, this work represents the largest molecular analysis of USC tumors to date and showed an increased expression of immune checkpoint genes in USC tumors. These findings provide evidence for further investigation into immune checkpoint inhibitors in USC tumors.