Catarina Alisa Kunze

Charité - Universitätsmedizin Berlin

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Carsten Denkert

Philipps University of Marburg

David Horst

Charité - Universitätsmedizin Berlin

Elena Ioana Braicu

Charité - Universitätsmedizin Berlin

Jalid Sehouli

Charité - Universitätsmedizin Berlin

Eliane T. Taube

Charité - Universitätsmedizin Berlin

Hagen Kulbe

Charité - Universitätsmedizin Berlin

Wolfgang Schmitt

Charité - Universitätsmedizin Berlin

Silvia Darb‐Esfahani

Charité - Universitätsmedizin Berlin

Bruno V. Sinn

Charité - Universitätsmedizin Berlin

Paul Jank

Philipps University of Marburg

Cooperative Institutions

Charité - Universitätsmedizin Berlin

131

Humboldt-Universität zu Berlin

106

Freie Universität Berlin

102

Heidelberg University

Berlin Institute of Health at Charité - Universitätsmedizin Berlin

University Hospital Heidelberg

Ludwig-Maximilians-Universität München

German Cancer Research Center

University Medical Center Hamburg-Eppendorf

Universität Hamburg

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Prognostic value of the De Ritis ratio in patients with NET undergoing retreatment with Lutetium-177-DOTATOC-PRRT

Nuklearmedizin - NuclearMedicine (2022)

Markus Galler Julian M.M. Rogasch Christoph Wetz Uli Fehrenbach Catarina Alisa Kunze

Ziel/Aim Retreatment with Lutetium-177-DOTATOC/DOTATATE-PRRT has shown a potential benefit in patients who have progressed after initial therapy cycles with a safety profile similar to the initial treatment1. This is to evaluate the De Ritis ratio (aspartate aminotransferase [AST]/alanine aminotransferase [ALT]) and progression-free survival (PFS) after initial PRRT as predictors of the PFS following retreatment.

Lutetium

Alanine aminotransferase

Radionuclide therapy

10.1055/s-0042-1746102

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Citations (0)

Cytokeratin 5/6 expression, prognosis, and association with estrogen receptor α in high-grade serous ovarian carcinoma

Human Pathology (2017)

Eliane T. Taube Carsten Denkert Jalid Sehouli U Unger Catarina Alisa Kunze

Serous carcinoma

10.1016/j.humpath.2017.03.020

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Citations (12)

Prognostic significance of Ki-67 levels and hormone receptor expression in low-grade serous ovarian carcinoma: an investigation of the Tumor Bank Ovarian Cancer Network

Human Pathology (2018)

Jalid Sehouli Elena Ioana Braicu Rolf Richter Carsten Denkert Paul Jank

Serous carcinoma

Progesterone receptor

Ki-67

Cut-off

10.1016/j.humpath.2018.10.020

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Citations (26)

Influence of Lymphatic, Microvascular and Perineural Invasion on Oncological Outcome in Patients with Neuroendocrine Tumors of the Small Intestine

Cancers (2024)

Frederike Butz Agata Dukaczewska Catarina Alisa Kunze Janina Maren Krömer Lisa Reinhard

For the histopathological work-up of resected neuroendocrine tumors of the small intestine (siNET), the determination of lymphatic (LI), microvascular (VI) and perineural (PnI) invasion is recommended. Their association with poorer prognosis has already been demonstrated in many tumor entities. However, the influence of LI, VI and PnI in siNET has not been sufficiently described yet. A retrospective analysis of all patients treated for siNET at the ENETS Center of Excellence Charité-Universitätsmedizin Berlin, from 2010 to 2020 was performed (

Perineural invasion

Lymphovascular invasion

10.3390/cancers16020305

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MALDI‐Imaging for Classification of Epithelial Ovarian Cancer Histotypes from a Tissue Microarray Using Machine Learning Methods

PROTEOMICS - CLINICAL APPLICATIONS (2018)

Oliver Klein Frederic Kanter Hagen Kulbe Paul Jank Carsten Denkert

Precise histological classification of epithelial ovarian cancer (EOC) has immanent diagnostic and therapeutic consequences, but remains challenging in histological routine. The aim of this pilot study is to examine the potential of matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry in combination with machine learning methods to classify EOC histological subtypes from tissue microarray.Formalin-fixed-paraffin-embedded tissue of 20 patients with ovarian clear-cell, 14 low-grade serous, 19 high-grade serous ovarian carcinomas, and 14 serous borderline tumors are analyzed using MALDI-Imaging. Classifications are computed by linear discriminant analysis (LDA), support vector machines with linear (SVM-lin) and radial basis function kernels (SVM-rbf), a neural network (NN), and a convolutional neural network (CNN).MALDI-Imaging and machine learning methods result in classification of EOC histotypes with mean accuracy of 80% for LDA, 80% SVM-lin, 74% SVM-rbf, 83% NN, and 85% CNN. Based on sensitivity (69-100%) and specificity (90-99%), CCN and NN are most suited to EOC classification.The pilot study demonstrates the potential of MALDI-Imaging derived proteomic classifiers in combination with machine learning algorithms to discriminate EOC histotypes. Applications may support the development of new prognostic parameters in the assessment of EOC.

Tissue microarray

10.1002/prca.201700181

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Citations (54)

Hemicolectomy versus appendectomy for patients with appendiceal neuroendocrine tumours 1–2 cm in size: a retrospective, Europe-wide, pooled cohort study

The Lancet Oncology (2023)

Cédric Nesti Konstantin Bräutigam Marta Benavent Laura Bernal Hessa Boharoon

Right hemicolectomy

10.1016/s1470-2045(22)00750-1

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Citations (47)

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

Human Pathology (2023)

Svenja Kolb Inga Hoffmann Nanna Monjé Mihnea P. Dragomir Paul Jank

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.

Serous carcinoma

10.1016/j.humpath.2023.09.001

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Citations (2)

Patient-derived tumoroids of advanced high-grade neuroendocrine neoplasms mimic patient chemotherapy responses and guide the design of personalized combination therapies

bioRxiv (Cold Spring Harbor Laboratory) (2022)

Simon April-Monn Katharina Detjen Philipp Kirchner Konstantin Bräutigam Mafalda Trippel

ABSTRACT There are no therapeutic predictive biomarkers or representative preclinical models for high-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN), a highly aggressive, fatal, and heterogeneous epithelial malignancy. We established patient-derived (PD) tumoroids from biobanked tissue samples of advanced high-grade GEP-NEN patients and applied this model for targeted rapid ex vivo pharmacotyping, next-generation sequencing, and perturbational profiling. We used tissue-matched PD tumoroids to profile individual patients, compared ex vivo drug response to patients’ clinical response to chemotherapy, and investigated treatment-induced adaptive stress responses. PD tumoroids recapitulated biological key features of high-grade GEP-NEN and mimicked clinical response to cisplatin and temozolomide ex vivo . When we investigated treatment-induced adaptive stress responses in PD tumoroids in silico, we discovered and functionally validated Lysine demethylase 5A and interferon-beta, which act synergistically in combination with cisplatin. Since ex vivo drug response in PD tumoroids matched clinical patient responses to standard-of-care chemotherapeutics for GEP-NEN, our rapid and functional precision oncology approach could expand personalized therapeutic options for patients with advanced high-grade GEP-NEN.

Ex vivo

Temozolomide

10.1101/2022.12.10.519855

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Citations (1)

Determination of fetal age by immunohistochemical estimation of surfactant-producing alveolar type II cells

Forensic Science International (1992)

P. Betz Michael Nerlich J. Wilske I. Wiest Catarina Alisa Kunze

Alveolar cells

Pulmonary alveolus

10.1016/0379-0738(92)90195-3

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