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

被引:1
作者
Kolb, Svenja [1 ]
Hoffmann, Inga [2 ,3 ,4 ]
Monje, Nanna [2 ,3 ,4 ]
Dragomir, Mihnea P. [2 ,3 ,4 ,5 ,6 ,7 ]
Jank, Paul [6 ]
Bischoff, Philip [2 ,3 ,4 ]
Keunecke, Carlotta [3 ,4 ,8 ]
Pohl, Jonathan [2 ,3 ,4 ]
Kunze, Catarina Alisa [2 ,3 ,4 ]
Marchenko, Sofya [2 ,3 ,4 ]
Schmitt, Wolfgang D. [2 ,3 ,4 ]
Kulbe, Hagen [3 ,4 ,8 ,9 ,10 ]
Sers, Christine [2 ,3 ,4 ]
Sehouli, Jalid [3 ,4 ,8 ,9 ,10 ]
Braicu, Elena Ioana [3 ,4 ,8 ,9 ,10 ]
Denkert, Carsten [11 ,12 ]
Darb-Esfahani, Silvia [13 ,14 ]
Horst, David [2 ,3 ,4 ]
Sinn, Bruno V. [1 ]
Taube, Eliane T. [2 ,3 ,4 ,15 ]
机构
[1] Vivantes Hosp Neukolln, Dept Gynecol, Vivantes Netzwerk Gesundheit GmbH Berlin, D-12351 Berlin, Germany
[2] Charite Univ Med Berlin, Inst Pathol, D-10117 Berlin, Germany
[3] Free Univ Berlin, D-10117 Berlin, Germany
[4] Humboldt Univ, D-10117 Berlin, Germany
[5] Charite Univ Med Berlin, Berlin Inst Hlth, D-10117 Berlin, Germany
[6] German Canc Consortium DKTK, Partner Site Berlin, D-69120 Heidelberg, Germany
[7] German Canc Res Ctr, D-69120 Heidelberg, Germany
[8] European Competence Ctr Ovarian Canc, Dept Gynecol, Charite Univ Med Berlin, D-10117 Berlin, Germany
[9] Charite Univ Med Berlin, Tumorbank Ovarian Canc Network, D-10117 Berlin, Germany
[10] Berlin Inst Hlth, D-10117 Berlin, Germany
[11] Philipps Univ Marburg, Inst Pathol, Inst Pathol, D-35043 Marburg, Germany
[12] Univ Hosp Marburg, D-35043 Marburg, Germany
[13] MVZ Pathol Spandau, D-13589 Berlin, Spandau, Germany
[14] MVZ Pathol Berlin Buch, D-13125 Berlin, Germany
[15] Charite Hosp, Inst Pathol, Campus Mitte,Charitepl 1, D-10117 Berlin, Germany
关键词
HGSOC; HGSC; LRP1B; Tubo-ovarian carcinoma; Prognostic marker; OVARIAN-CANCER; EXPRESSION; MIGRATION; MUTATION; DELETION; PATHWAY;
D O I
10.1016/j.humpath.2023.09.001
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
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 prog-nostic 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 meta-bolism in advanced HGSC, especially regarding liposomal medications.(c) 2023 The Authors. Published by Elsevier Inc.
引用
收藏
页码:158 / 168
页数:11
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