RB Loss in p53 Abnormal Endometrial Carcinoma: Histological and Clinicopathological Correlates.

Autor:	Serbes ED; Department of Pathology, Van Research and Training Hospital, Van, Turkiye., Horeweg N; Department of Radiation Oncology, Leiden University Medical Center, Leiden, The Netherlands., Parra-Herran C; Division of Women's and Perinatal Pathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., van Rijnsoever R; Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands., Jobsen JJ; Department of Radiation Oncology, Medisch Spectrum Twente, Enschede, The Netherlands., Jurgenliemk-Schulz I; Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands., Kuijsters N; Department of Radiation Oncology, Maastro Clinic, Maastricht, The Netherlands., Nout RA; Department of Radiation Oncology, Leiden University Medical Center, Leiden, The Netherlands., Haverkort MAD; Department of Radiation Oncology, Radiotherapiegroep, Arnhem, The Netherlands., Powell ME; Department of Clinical Oncology, Barts Health NHS Trust, London, United Kingdom., Khaw P; Department of Radiation Oncology, Peter MacCallum Cancer Center, Melbourne, Victoria, Australia., Plante M; Department of Obstetrics, Gynecology, and Reproduction, Faculty of Medicine, Laval University, Quebec City, Quebec, Canada., Genestie C; Department of Pathology, Gustave Roussy, Villejuif, Île-de-France, France., Nijman HW; Department of Gynecology, University Medical Center Groningen, Groningen, The Netherlands., Creutzberg CL; Department of Radiation Oncology, Leiden University Medical Center, Leiden, The Netherlands., Bosse T; Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: T.Bosse@lumc.nl., Kramer CJH; Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Jazyk:	angličtina
Zdroj:	Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [Mod Pathol] 2024 Nov 20, pp. 100660. Date of Electronic Publication: 2024 Nov 20.
DOI:	10.1016/j.modpat.2024.100660
Abstrakt:	Of the four molecular subtypes of endometrial cancer (EC), p53-abnormal (p53abn) EC is associated with abundant copy number alterations (CNAs) and the worst clinical outcome. Patients with p53abn EC have the highest risk of disease recurrence and death, independent of tumor grade and histologic subtype. Currently, all invasive p53abn ECs are considered high risk, and no prognostic biomarkers have yet been found that can aid in clinical management. Here, we aimed to test whether loss of retinoblastoma protein (RB) expression using immunohistochemistry (IHC) has potential for prognostic refinement of p53abn EC. A large cohort of 227 p53abn ECs collected from the PORTEC-1/2/3 clinical trials and the MST cohort study was investigated, and RB loss was identified in 7.0% (n=16/227). RB-lost p53abn ECs were predominantly high-grade endometrioid ECs (n=6, 37.5%) and carcinosarcomas with endometrioid-type epithelial component (n=5, 31.3%). Histologically, RB-lost p53abn EC were typified by high grade nuclear atypia (n=16, 100%), predominantly solid growth pattern (n=15/16, 93.8%), and polypoid growth (n=9/16, 56.3%). Copy number loss involving the RB1 locus was identified in the majority of RB-lost p53abn EC (n=13/14, 92.9%), explaining the loss of RB expression. Comparative analysis also showed that RB-lost p53abn EC were diagnosed at earlier stages than RB-retained p53abn EC (p=0.014). Interestingly, RB-lost p53abn EC showed prolonged time to overall recurrence (p=0.038), even within stage I alone (p=0.040). These findings highlight distinct morphomolecular features in RB-lost p53abn EC and confirm the utility of RB IHC as a surrogate for molecular RB1 alterations. This is the first study to show the potential use of RB in prognostic refinement of p53abn EC, although validation is warranted. (Copyright © 2024. Published by Elsevier Inc.)
Databáze:	MEDLINE
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