LRP1B-a prognostic marker in tubo-ovarian high-grade serous carcinoma.


Journal

Human pathology
ISSN: 1532-8392
Titre abrégé: Hum Pathol
Pays: United States
ID NLM: 9421547

Informations de publication

Date de publication:
Nov 2023
Historique:
received: 30 07 2023
revised: 14 09 2023
accepted: 18 09 2023
medline: 28 11 2023
pubmed: 25 9 2023
entrez: 24 9 2023
Statut: ppublish

Résumé

Low-density lipoprotein (LDL) receptor-related protein 1B (LRP1B) is a member of the LDL receptor family and has often been discussed as a tumor suppressor gene, as its down-regulation is correlated with a poor prognosis in multiple carcinoma entities. Due to the high metastasis rate into the fatty peritoneal cavity and current research findings showing a dysregulation of lipid metabolism in tubo-ovarian high-grade serous carcinoma (HGSC), we questioned the prognostic impact of the LRP1B protein expression. We examined a well-characterized large cohort of 571 patients with primary HGSC and analyzed the LRP1B protein expression via immunohistochemical staining (both in tumor and stroma cells separately), performed precise bioimage analysis with QuPath, and calculated the prognostic impact using SPSS. Our results demonstrate that LRP1B functions as a significant prognostic marker for overall survival (OS) and progression-free survival (PFS) in HGSC on the protein level. High cytoplasmic expression of LRP1B in tumor, stroma, and combined tumor and stroma cells has a significantly positive association with a mean prolongation of the OS by 42 months (P = .005), 29 months (P = .005), and 25 months (P = .001), respectively. Additionally, the mean PFS was 18 months longer in tumor (P = .002), 19 months in stroma (P = .004), and 19 months in both cell types combined (P = .01). Our results remained significant in multivariate analysis. We envision LRP1B as a potential prognostic tool that could help us understand the functional role of lipid metabolism in advanced HGSC, especially regarding liposomal medications.

Identifiants

pubmed: 37742945
pii: S0046-8177(23)00186-7
doi: 10.1016/j.humpath.2023.09.001
pii:
doi:

Substances chimiques

LRP1B protein, human 0
Receptors, LDL 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

158-168

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Auteurs

Svenja Kolb (S)

Department of Gynecology, Vivantes Netzwerk für Gesundheit GmbH Berlin, Vivantes Hospital Neukölln, 12351, Berlin, Germany.

Inga Hoffmann (I)

Institute of Pathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, 10117, Berlin, Germany.

Nanna Monjé (N)

Institute of Pathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, 10117, Berlin, Germany.

Mihnea P Dragomir (MP)

Institute of Pathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, 10117, Berlin, Germany; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, 10117, Berlin, Germany; German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.

Paul Jank (P)

Institute of Pathology, Philipps-University Marburg and University Hospital Marburg, 35043 Marburg, Germany.

Philip Bischoff (P)

Institute of Pathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, 10117, Berlin, Germany.

Carlotta Keunecke (C)

Department of Gynecology, European Competence Center for Ovarian Cancer, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.

Jonathan Pohl (J)

Institute of Pathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, 10117, Berlin, Germany.

Catarina Alisa Kunze (CA)

Institute of Pathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, 10117, Berlin, Germany.

Sofya Marchenko (S)

Institute of Pathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, 10117, Berlin, Germany.

Wolfgang D Schmitt (WD)

Institute of Pathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, 10117, Berlin, Germany.

Hagen Kulbe (H)

Department of Gynecology, European Competence Center for Ovarian Cancer, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany; Tumorbank Ovarian Cancer Network, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.

Christine Sers (C)

Institute of Pathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, 10117, Berlin, Germany.

Jalid Sehouli (J)

Department of Gynecology, European Competence Center for Ovarian Cancer, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany; Tumorbank Ovarian Cancer Network, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.

Elena Ioana Braicu (EI)

Department of Gynecology, European Competence Center for Ovarian Cancer, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany; Tumorbank Ovarian Cancer Network, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.

Carsten Denkert (C)

Institute of Pathology, Philipps-University Marburg and University Hospital Marburg, 35043 Marburg, Germany.

Silvia Darb-Esfahani (S)

MVZ Pathologie Spandau, 13589 Berlin, Spandau, Germany; MVZ Pathologie Berlin-Buch, 13125 Berlin, Germany.

David Horst (D)

Institute of Pathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, 10117, Berlin, Germany.

Bruno V Sinn (BV)

Institute of Pathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, 10117, Berlin, Germany.

Eliane T Taube (ET)

Institute of Pathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, 10117, Berlin, Germany. Electronic address: eliane.taube@charite.de.

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Classifications MeSH