KRT18 as a Novel Biomarker of Urothelial Papilloma while Evaluating Low-Grade Papillary Urothelial Neoplasms: Bi-Center Analysis.

Autor: Jung M; Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea., Kim B; Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Republic of Korea., Lee JS; Department of Pathology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea., Kim JY; Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea., Han D; Transdisciplinary Department of Medicine and Advanced Technology, Seoul National University Hospital, Seoul, Republic of Korea.; Proteomics Core Facility, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea., Kim K; Transdisciplinary Department of Medicine and Advanced Technology, Seoul National University Hospital, Seoul, Republic of Korea., Yang S; Transdisciplinary Department of Medicine and Advanced Technology, Seoul National University Hospital, Seoul, Republic of Korea., Kim EN; Department of Pathology, Seoul National University Hospital, Seoul, Republic of Korea., Kim H; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA., Nikas IP; Medical School, University of Cyprus, Nicosia, Cyprus., Yang S; Department of Pathology, Seoul National University Hospital, Seoul, Republic of Korea.; Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea., Moon KC; Department of Pathology, Seoul National University Hospital, Seoul, Republic of Korea.; Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.; Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea., Lee H; Department of Radiation Oncology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea., Ryu HS; Department of Pathology, Seoul National University Hospital, Seoul, Republic of Korea.; Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.; Cancer Research Institute, Seoul National University, Seoul, Republic of Korea.
Jazyk: angličtina
Zdroj: Pathobiology : journal of immunopathology, molecular and cellular biology [Pathobiology] 2024 Aug 27, pp. 1-12. Date of Electronic Publication: 2024 Aug 27.
DOI: 10.1159/000540926
Abstrakt: Introduction: Although urothelial papilloma (UP) is an indolent papillary neoplasm that can mimic the morphology of low-grade papillary urothelial carcinoma (PUC), there is no immunomarker to differentiate reliably these two entities. In addition, the molecular characteristics of UP are not fully understood.
Methods: We conducted an in-depth proteomic analysis of papillary urothelial lesions (n = 31), including UP and PUC along with normal urothelium. Protein markers distinguishing UP and PUC were selected with machine learning analysis, followed by internal and external validation using immunohistochemistry.
Results: In the proteomic analysis, UP and PUC showed overlapping proteomic profiles. We identified EHD4 and KRT18 as candidate diagnostic biomarkers of UP. Through immunohistochemical validation in two independent cohorts (n = 120), KRT18 was suggested as a novel UP diagnostic marker, able to differentiate UP from low-grade PUC. We also found that 3.5% of patients with UP developed urothelial carcinoma in subsequent resections, supporting the malignant potential of UP. KRT18 downregulation was significantly associated with UPs subsequently progressing to urothelial carcinoma, following their initial diagnosis.
Conclusion: This is the first study that successfully revealed UPs comprehensive proteomic landscape, while it also identified KRT18 as a potential diagnostic biomarker of UP.
(© 2024 S. Karger AG, Basel.)
Databáze: MEDLINE