23 results on '"Kunze, Catarina Alisa"'
Search Results
2. High EVI1 and PARP1 expression as favourable prognostic markers in high-grade serous ovarian carcinoma
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Jank, Paul, Leichsenring, Jonas, Kolb, Svenja, Hoffmann, Inga, Bischoff, Philip, Kunze, Catarina Alisa, Dragomir, Mihnea P., Gleitsmann, Moritz, Jesinghaus, Moritz, Schmitt, Wolfgang D., Kulbe, Hagen, Sers, Christine, Stenzinger, Albrecht, Sehouli, Jalid, Braicu, Ioana Elena, Westhoff, Christina, Horst, David, Denkert, Carsten, Gröschel, Stefan, and Taube, Eliane T.
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- 2023
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3. Prognostic value of regulatory T cells and T helper 17 cells in high grade serous ovarian carcinoma
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Marchenko, Sofya, Piwonski, Iris, Hoffmann, Inga, Sinn, Bruno Valentin, Kunze, Catarina Alisa, Monjé, Nanna, Pohl, Jonathan, Kulbe, Hagen, Schmitt, Wolfgang Daniel, Darb-Esfahani, Sylvia, Braicu, Elena Ioana, von Brünneck, Ann-Christin, Sehouli, Jalid, Denkert, Carsten, Horst, David, Jöhrens, Korinna, and Taube, Eliane Tabea
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- 2023
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4. LRP1B—a prognostic marker in tubo-ovarian high-grade serous carcinoma
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Kolb, Svenja, Hoffmann, Inga, Monjé, Nanna, Dragomir, Mihnea P., Jank, Paul, Bischoff, Philip, Keunecke, Carlotta, Pohl, Jonathan, Kunze, Catarina Alisa, Marchenko, Sofya, Schmitt, Wolfgang D., Kulbe, Hagen, Sers, Christine, Sehouli, Jalid, Braicu, Elena Ioana, Denkert, Carsten, Darb-Esfahani, Silvia, Horst, David, Sinn, Bruno V., and Taube, Eliane T.
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- 2023
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5. Increased expression of IDO1 is associated with improved survival and increased number of TILs in patients with high-grade serous ovarian cancer
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Hoffmann, Inga, Dragomir, Mihnea P., Monjé, Nanna, Keunecke, Carlotta, Kunze, Catarina Alisa, Schallenberg, Simon, Marchenko, Sofya, Schmitt, Wolfgang D., Kulbe, Hagen, Sehouli, Jalid, Braicu, Ioana Elena, Jank, Paul, Denkert, Carsten, Darb-Esfahani, Silvia, Horst, David, Sinn, Bruno V., Sers, Christine, Bischoff, Philip, and Taube, Eliane T.
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- 2023
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6. Hemicolectomy versus appendectomy for patients with appendiceal neuroendocrine tumours 1–2 cm in size: a retrospective, Europe-wide, pooled cohort study
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Nesti, Cédric, Bräutigam, Konstantin, Benavent, Marta, Bernal, Laura, Boharoon, Hessa, Botling, Johan, Bouroumeau, Antonin, Brcic, Iva, Brunner, Maximilian, Cadiot, Guillaume, Camara, Maria, Christ, Emanuel, Clerici, Thomas, Clift, Ashley K, Clouston, Hamish, Cobianchi, Lorenzo, Ćwikła, Jarosław B, Daskalakis, Kosmas, Frilling, Andrea, Garcia-Carbonero, Rocio, Grozinsky-Glasberg, Simona, Hernando, Jorge, Hervieu, Valérie, Hofland, Johannes, Holmager, Pernille, Inzani, Frediano, Jann, Henning, Jimenez-Fonseca, Paula, Kaçmaz, Enes, Kaemmerer, Daniel, Kaltsas, Gregory, Klimacek, Branislav, Knigge, Ulrich, Kolasińska-Ćwikła, Agnieszka, Kolb, Walter, Kos-Kudła, Beata, Kunze, Catarina Alisa, Landolfi, Stefania, La Rosa, Stefano, López, Carlos López, Lorenz, Kerstin, Matter, Maurice, Mazal, Peter, Mestre-Alagarda, Claudia, del Burgo, Patricia Morales, van Dijkum, Els J M Nieveen, Oleinikov, Kira, Orci, Lorenzo A, Panzuto, Francesco, Pavel, Marianne, Perrier, Marine, Reims, Henrik Mikael, Rindi, Guido, Rinke, Anja, Rinzivillo, Maria, Sagaert, Xavier, Satiroglu, Ilker, Selberherr, Andreas, Siebenhüner, Alexander R, Tesselaar, Margot E T, Thalhammer, Michael J, Thiis-Evensen, Espen, Toumpanakis, Christos, Vandamme, Timon, van den Berg, José G, Vanoli, Alessandro, van Velthuysen, Marie-Louise F, Verslype, Chris, Vorburger, Stephan A, Lugli, Alessandro, Ramage, John, Zwahlen, Marcel, Perren, Aurel, and Kaderli, Reto M
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- 2023
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7. COVID-19: Autopsy findings in six patients between 26 and 46 years of age
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Greuel, Selina, Ihlow, Jana, Dragomir, Mihnea-Paul, Streit, Simon, Corman, Victor Max, Haberbosch, Linus, Winkler, David, Meinhardt, Jenny, Aschman, Tom, Schneider, Julia, Trotsyuk, Iryna, Kunze, Catarina Alisa, Maurer, Lukas, Radbruch, Helena, Heppner, Frank L., Horst, David, and Elezkurtaj, Sefer
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- 2021
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8. Causes of death and comorbidities in hospitalized patients with COVID-19
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Elezkurtaj, Sefer, Greuel, Selina, Ihlow, Jana, Michaelis, Edward Georg, Bischoff, Philip, Kunze, Catarina Alisa, Sinn, Bruno Valentin, Gerhold, Manuela, Hauptmann, Kathrin, Ingold-Heppner, Barbara, Miller, Florian, Herbst, Hermann, Corman, Victor Max, Martin, Hubert, Radbruch, Helena, Heppner, Frank L., and Horst, David
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- 2021
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9. Influence of Lymphatic, Microvascular and Perineural Invasion on Oncological Outcome in Patients with Neuroendocrine Tumors of the Small Intestine.
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Butz, Frederike, Dukaczewska, Agata, Kunze, Catarina Alisa, Krömer, Janina Maren, Reinhard, Lisa, Jann, Henning, Fehrenbach, Uli, Müller-Debus, Charlotte Friederieke, Skachko, Tatiana, Pratschke, Johann, Goretzki, Peter E., Mogl, Martina T., and Dobrindt, Eva Maria
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INTESTINAL tumors ,DISEASE progression ,CANCER invasiveness ,LYMPH nodes ,RETROSPECTIVE studies ,CANCER relapse ,SURGICAL complications ,METASTASIS ,CANCER patients ,COMPARATIVE studies ,NEUROENDOCRINE tumors ,SMALL intestine ,DESCRIPTIVE statistics ,CELL lines ,PROGRESSION-free survival ,HEPATOCELLULAR carcinoma - Abstract
Simple Summary: Lymphatic (LI), microvascular (VI) and perineural invasion (PnI) have been determined as indicators for aggressive tumor behavior and worse outcome in many solid tumors. In neuroendocrine tumors of the small intestine (siNET), some prognosis-defining factors have been well established, but the role of LI, VI and PnI remains incompletely understood so far. The aim of our retrospective study was to elucidate the role of lymphatic, microvascular and perineural invasion in the oncological outcome in siNET. We found that lymphatic, microvascular and perineural invasion led to earlier disease recurrence and postoperative disease progression. We therefore promote the routine description of these histopathological parameters for considerations on adjuvant treatment and follow-up. 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 (n = 510). Patients who did not undergo primary resection or had G3 tumors were excluded. In the entire cohort (n = 161), patients with LI, VI and PnI status had more distant metastases (48.0% vs. 71.4%, p = 0.005; 47.1% vs. 84.4%, p < 0.001; 34.2% vs. 84.7%, p < 0.001) and had lower rates of curative surgery (58.0% vs. 21.0%, p < 0.001; 48.3% vs. 16.7%, p < 0.001; 68.4% vs. 14.3%, p < 0.001). Progression-free survival was significantly reduced in patients with LI, VI or PnI compared to patients without. This was also demonstrated in patients who underwent curative surgery. Lymphatic, vascular and perineural invasion were associated with disease progression and recurrence in patients with siNET, and these should therefore be included in postoperative treatment considerations. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Wilms tumor protein 1 (WT1) — Not only a diagnostic but also a prognostic marker in high-grade serous ovarian carcinoma
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Taube, Eliane Tabea, Denkert, Carsten, Sehouli, Jalid, Kunze, Catarina Alisa, Dietel, Manfred, Braicu, Ioana, Letsch, Anne, and Darb-Esfahani, Silvia
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- 2016
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11. Outcome of immunotherapy in adrenocortical carcinoma : A retrospective cohort study
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Remde, Hanna, Schmidt-Pennington, Laura, Reuter, Miriam, Landwehr, Laura-Sophie, Jensen, Marie, Lahner, Harald, Kimpel, Otilia, Altieri, Barbara, Laubner, Katharina, Schreiner, Jochen, Bojunga, Joerg, Kircher, Stefan, Kunze, Catarina Alisa, Pohrt, Anne, Teleanu, Maria-Veronica, Hübschmann, Daniel, Stenzinger, Albrecht, Glimm, Hanno, Fröhling, Stefan, Fassnacht, Martin, Mai, Knut, and Kroiss, Matthias
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Medizin - Published
- 2023
12. Low Expression of RGS2 Promotes Poor Prognosis in High-Grade Serous Ovarian Cancer
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Ihlow, Jana, primary, Monjé, Nanna, additional, Hoffmann, Inga, additional, Bischoff, Philip, additional, Sinn, Bruno Valentin, additional, Schmitt, Wolfgang Daniel, additional, Kunze, Catarina Alisa, additional, Darb-Esfahani, Sylvia, additional, Kulbe, Hagen, additional, Braicu, Elena Ioana, additional, Sehouli, Jalid, additional, Denkert, Carsten, additional, Horst, David, additional, and Taube, Eliane Tabea, additional
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- 2022
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13. Prognostic value of regulatory T cells and T helper 17 cells in high grade serous ovarian carcinoma
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Marchenko, Sofya, primary, Piwonski, Iris, additional, Hoffmann, Inga, additional, Sinn, Bruno Valentin, additional, Kunze, Catarina Alisa, additional, Monjé, Nanna, additional, Pohl, Jonathan, additional, Kulbe, Hagen, additional, Schmitt, Wolfgang Daniel, additional, Darb-Esfahani, Sylvia, additional, Braicu, Elena Ioana, additional, von Brünneck, Ann-Christin, additional, Sehouli, Jalid, additional, Denkert, Carsten, additional, Horst, David, additional, Jöhrens, Korinna, additional, and Taube, Eliane Tabea, additional
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- 2022
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14. 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
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Sehouli, Jalid, Braicu, Elena Ioana, Richter, Rolf, Denkert, Carsten, Jank, Paul, Jurmeister, Philipp Sebastian, Kunze, Catarina Alisa, Budczies, Jan, Darb-Esfahani, Sylvia, Schmitt, Wolfgang Daniel, Traut, Alexander, Grabowski, Jacek, Taube, Eliane Tabea, Plett, Helmut, and Taube, ElianeTabea
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Adult ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Medizin ,Estrogen receptor ,Pathology and Forensic Medicine ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Ovarian carcinoma ,Internal medicine ,Progesterone receptor ,Biomarkers, Tumor ,medicine ,Humans ,Aged ,Retrospective Studies ,Aged, 80 and over ,Ovarian Neoplasms ,biology ,business.industry ,Middle Aged ,Prognosis ,medicine.disease ,Immunohistochemistry ,Progression-Free Survival ,Cystadenocarcinoma, Serous ,Survival Rate ,Serous fluid ,Ki-67 Antigen ,030104 developmental biology ,Receptors, Estrogen ,Hormone receptor ,030220 oncology & carcinogenesis ,Ki-67 ,biology.protein ,Female ,Cancer biomarkers ,Receptors, Progesterone ,business ,Ovarian cancer - Abstract
Summary Low-grade serous ovarian carcinoma (LGSOC) has recently come up as a distinct rare entity of epithelial ovarian cancer. Predictive and prognostic markers are not well studied yet. Because Ki-67 and hormone receptors (HR) have been established as relevant cancer biomarkers in several malignant tumors, we evaluated Ki-67 and HR expression rates by immunohistochemistry in 68 patients with LGSOC. We used a standardized cutoff finder algorithm to analyze prognostic significance for overall survival (OS) and progression-free survival (PFS). Cox regression showed a significant continuous decrease in OS for higher proliferation rates with an HR of 1.07% (95% confidence interval, 1.01%-3.67%; P = .048) but not in PFS (P = .86). Cutoff finder analysis revealed the best possible cutoff for OS at 6.28% (P = .04) and for PFS at 1.85% proliferative activity (P = .04). Estrogen receptors (ERs) were expressed in most LGSOC patients (n = 61; 89.7%), progesterone receptor (PR) in about half of patients (n = 33; 48.5%). For both ER/PR, a statistically significant cutoff for PFS could be determined, which was at 75% of positive tumor cells for ER (P = .02) and at 15% of positive tumor cells for PR (P = .03). For OS, HR expression showed a tendency toward better OS for HR-positive tumors but did not turn out statistically significant. Our results show that Ki-67 is a valuable prognostic marker in the subgroup of LGSOC. We could also show that most LGSOCs express HRs but that this expression is associated with a better PFS, a finding valuable in times of antihormonal therapy in LGSOC.
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- 2019
15. Causes of death and comorbidities in hospitalized patients with COVID-19
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Elezkurtaj, Sefer, Greuel, Selina, Ihlow, Jana, Michaelis, Edward Georg, Bischoff, Philip, Kunze, Catarina Alisa, Sinn, Bruno Valentin, Gerhold, Manuela, Hauptmann, Kathrin, Ingold-Heppner, Barbara, Miller, Florian, Herbst, Hermann, Corman, Victor Max, Martin, Hubert, Radbruch, Helena, Heppner, Frank L., and Horst, David
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Adult ,Male ,virology [COVID-19] ,statistics & numerical data [Hospitals, Teaching] ,Science ,Multiple Organ Failure ,Myocardial Ischemia ,Diseases ,causes of death ,Comorbidity ,Pathogenesis ,epidemiology [Hypertension] ,epidemiology [Myocardial Ischemia] ,Article ,therapy [COVID-19] ,Cause of Death ,Humans ,complications [COVID-19] ,Hospital Mortality ,Obesity ,Prospective Studies ,Hospitals, Teaching ,Aged ,Aged, 80 and over ,epidemiology [Obesity] ,SARS-CoV-2 ,virology [Shock, Septic] ,mortality [Shock, Septic] ,hospitalized patients ,COVID-19 ,Middle Aged ,epidemiology [Berlin] ,Shock, Septic ,isolation & purification [SARS-CoV-2] ,mortality [COVID-19] ,Berlin ,mortality [Multiple Organ Failure] ,Risk factors ,virology [Multiple Organ Failure] ,Hypertension ,Medicine ,Female ,Autopsy ,ddc:600 ,600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit - Abstract
Infection by the new corona virus strain SARS-CoV-2 and its related syndrome COVID-19 has been associated with more than two million deaths worldwide. Patients of higher age and with preexisting chronic health conditions are at an increased risk of fatal disease outcome. However, detailed information on causes of death and the contribution of pre-existing health conditions to death yet is missing, which can be reliably established by autopsy only. We performed full body autopsies on 26 patients that had died after SARS-CoV-2 infection and COVID-19 at the Charité University Hospital Berlin, Germany, or at associated teaching hospitals. We systematically evaluated causes of death and pre-existing health conditions. Additionally, clinical records and death certificates were evaluated. We report findings on causes of death and comorbidities of 26 decedents that had clinically presented with severe COVID-19. We found that septic shock and multi organ failure was the most common immediate cause of death, often due to suppurative pulmonary infection. Respiratory failure due to diffuse alveolar damage presented as immediate cause of death in fewer cases. Several comorbidities, such as hypertension, ischemic heart disease, and obesity were present in the vast majority of patients. Our findings reveal that causes of death were directly related to COVID-19 in the majority of decedents, while they appear not to be an immediate result of preexisting health conditions and comorbidities. We therefore suggest that the majority of patients had died of COVID-19 with only contributory implications of preexisting health conditions to the mechanism of death.
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- 2020
16. Causes of Death and Comorbidities in Patients with COVID-19
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Elezkurtaj, Sefer, primary, Greuel, Selina, additional, Ihlow, Jana, additional, Michaelis, Edward, additional, Bischoff, Philip, additional, Kunze, Catarina Alisa, additional, Sinn, Bruno Valentin, additional, Gerhold, Manuela, additional, Hauptmann, Kathrin, additional, Ingold-Heppner, Barbara, additional, Miller, Florian, additional, Herbst, Hermann, additional, Corman, Victor Max, additional, Martin, Hubert, additional, Radbruch, Helena, additional, Heppner, Frank L., additional, and Horst, David, additional
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- 2020
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17. Effect of Celecoxib vs Placebo as Adjuvant Therapy on Disease-Free Survival Among Patients With Breast Cancer: The REACT Randomized Clinical Trial.
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Coombes, R. Charles, Tovey, Holly, Kilburn, Lucy, Mansi, Janine, Palmieri, Carlo, Bartlett, John, Hicks, Jonathan, Makris, Andreas, Evans, Abigail, Loibl, Sibylle, Denkert, Carsten, Murray, Elisabeth, Grieve, Robert, Coleman, Robert, Borley, Annabel, Schmidt, Marcus, Rautenberg, Beate, Kunze, Catarina Alisa, Rhein, Uwe, and Mehta, Keyur
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- 2021
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18. Cytokeratin 5/6 expression, prognosis, and association with estrogen receptor α in high-grade serous ovarian carcinoma
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Taube, Eliane Tabea, primary, Denkert, Carsten, additional, Sehouli, Jalid, additional, Unger, Ulrike, additional, Kunze, Catarina Alisa, additional, Budczies, Jan, additional, Dietel, Manfred, additional, Braicu, Elena, additional, and Darb-Esfahani, Silvia, additional
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- 2017
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19. Aldehyddehydrogenase 1 A1, Thymosin-β15A und Poly(ADP-Ribose)-Polymerase-1 als prognostische Marker im Ovarialkarzinom
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Kunze, Catarina Alisa
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ovarian carcinoma ,aldehyde dehydrogenase 1 A1 ,prognosis ,thymosin-β15A ,poly(ADP-ribose) polymerase-1 ,600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit - Abstract
Epitheliale Ovarialkarzinome stellen eine häufige gynäkologische Tumorerkrankung mit schlechter Prognose dar. In der vorliegenden Arbeit wurden daher die Marker Aldehyddehydrogenase 1 A1 (ALDH1A1), Thymosin-β15A (TMSB15A) und Poly(ADP-Ribose)-Polymerase-1 (PARP1), welche sich bereits im Mammakarzinom als Biomarker mit prädiktiver und prognostischer Relevanz erwiesen hatten, hinsichtlich ihres prognostischen Wertes in Ovarialkarzinomen untersucht. Der Schwerpunkt lag in der Untersuchung der Marker in Typ II Ovarialkarzinomen. Untersucht wurden insbesondere Korrelationen mit Überlebensdaten, wichtigen klinisch-pathologischen Faktoren sowie eine Änderung der Markerexpression im Krankheitsverlauf. Hierfür wurden Formalin- fixierte und in Paraffin eingebettete Gewebeproben von insgesamt 209 Patientinnen mit primären epithelialen Ovarialkarzinomen sowie 38 korrespondierende Rezidivtumoren untersucht. Auf mRNA-Ebene wurden die Marker mittels einer quantitativen real-time-PCR untersucht. Auf Proteinebene wurden immunhistochemische Färbungen an Tissue Microarrays durchgeführt. Es konnte gezeigt werden, dass die Proteinexpression des potentiellen Krebsstammzellmarkers ALDH1 einen signifikant ungünstigen Prognosefaktor in Typ II Ovarialkarzinomen darstellt. Darüber hinaus zeigten Tumoren die das ALDH1-Protein und den epidermalen Wachstumsfaktorrezeptor (EGFR) exprimierten die statistisch ungünstigsten Verläufe. Das aktinbindende Protein TMSB15, welches die zytoskelettgesteuerte Lokomotion und somit möglicherweise auch die Metastasierungsfähigkeit der Zelle beeinflussen kann, war lediglich univariat ein signifikant günstiger Prognosemarker. Auf mRNA-Ebene konnte kein Einfluss der TMSB15A-Expression auf das Überleben der Patientinnen beobachtet werden. Die PARP1 ist als wichtiger Mediator des Basenexzisionsweg in die DNA- Reparatur involviert. Es konnte weder auf mRNA- noch auf Proteinebene ein Einfluss von PARP1 auf die Prognose festgestellt werden. Gemessene PARP1-mRNA- und Proteinwerte waren jedoch signifikant in Rezidivtumoren gegenüber den korrespondieren Primärtumoren erhöht. Eine Assoziation von ALDH1 und EGFR wird in der Literatur bereits in BRCA1-defizienten Brustepithelien und tripel negativen Mammakarzinomen beschrieben. Die Ergebnisse der vorliegenden Arbeit weisen darauf hin, dass es sich bei ALDH1- und EGFR-exprimierenden Tumoren um eine besonders aggressive Subgruppe von Typ II Ovarialkarzinomen handelt für die alternative Therapien angezeigt sein könnten. Eine weitere Charakterisierung dieser Subgruppe zusammen mit dem BRCA1-Mutationsstatus wäre daher ein interessanter Aspekt für zukünftige Studien. Höhere PARP1-Level in Rezidivtumoren der untersuchten Patientenproben könnten durch eine erhöhte chromosomale Instabilität und somit erhöhte Aktivität des Basenexzisionsweges in diesen Tumoren erklärt werden. Die Inhibierung von PARP in Zellen, in denen die homologe Rekombination beispielsweise durch eine BRCA-Mutation gestört ist, kann zur selektiven Apoptose führen, weswegen die Wirkung von PARP- Inhibitoren derzeit in klinischen Studien untersucht wird. Dennoch ist unklar, welche Patientengruppen tatsächlich von dieser Therapie profitieren und die PARP1-Expression sollte als potentieller prädiktiver Faktor weiter untersucht werden., Epithelial ovarian carcinoma constitutes a frequent gynecologic malignancy with a poor prognosis. As aldehyde dehydrogenase 1 A1 (ALDH1A1), thymosin-β15A (TMSB15A) and poly(ADP-ribose) polymerase-1 (PARP1) have already proved to be prognostic and predictive biomarkers in breast cancer, the aim of this study was to evaluate these biomarkers in ovarian cancer with emphasis on type II ovarian carcinoma. In this context correlations with survival and clinicopathologic parameters were regarded as well as changes in marker expression during the course of disease. This study included 209 formalin- fixed and paraffin-embedded samples of patients with primary epithelial ovarian carcinoma and additional 38 specimens of corresponding relapse tumors. mRNA levels were quantified by quantitative real-time polymerase chain reaction. To determine the protein expression immunohistochemical staining was performed on tissue microarrays. In this study it was demonstrated that the potential cancer stem cell marker ALDH1 was a significant marker of poor prognosis in type II ovarian carcinoma. Furthermore ALDH1- and epidermal growth factor receptor (EGFR)-protein expressing tumors showed most unfavorable outcome compared to the other expression groups. The actin binding protein TMSB15 which is assumed to be involved in cytoskeleton mediated locomotion and metastasis was a significant favorable prognostic marker merely in univariate analysis. There was no association between TMSB15A mRNA expression and survival. As an important mediator of base excision repair pathway PARP1 is involved in DNA repair. Neither PARP1-mRNA nor cytoplasmatic or nuclear PARP-protein expression were associated with prognosis. However, PARP1 mRNA and nuclear protein expression were upregulated in relapse tumors compared to the corresponding primary tumors. A correlation of ALDH1 and EGFR expression in BRCA1-deficient breast epithelium and triple negative breast cancer has already been described in previous observations. The results of this study indicate that ALDH1 and EGFR expressing tumors represent a highly aggressive subgroup of type II ovarian carcinoma for which alternative treatment options might be indicated. Further characterization of this subgroup in combination with the BRCA mutation status represents an interesting subject for future studies. Higher PARP1 levels in relapse tumors might be explained by a higher chromosomal instability in these tumors. Inhibition of PARP in cells with defective homologous recombination due to BRCA mutation, for example, can lead to selective cell death, which is why the effect of PARP inhibitors is investigated in clinical studies to date. However it is still unclear which patients actually benefit from PARP inhibitor therapy so that the PARP1-expression should be further investigated as a predictive factor.
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- 2015
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20. Prognostic impact of programmed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor-infiltrating lymphocytes in ovarian high grade serous carcinoma
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Darb-Esfahani, Silvia, primary, Kunze, Catarina Alisa, additional, Kulbe, Hagen, additional, Sehouli, Jalid, additional, Wienert, Stephan, additional, Lindner, Judith, additional, Budczies, Jan, additional, Bockmayr, Michael, additional, Dietel, Manfred, additional, Denkert, Carsten, additional, Braicu, Ioana, additional, and Jöhrens, Korinna, additional
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- 2015
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21. Outcome of immunotherapy in adrenocortical carcinoma: a retrospective cohort study.
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Remde H, Schmidt-Pennington L, Reuter M, Landwehr LS, Jensen M, Lahner H, Kimpel O, Altieri B, Laubner K, Schreiner J, Bojunga J, Kircher S, Kunze CA, Pohrt A, Teleanu MV, Hübschmann D, Stenzinger A, Glimm H, Fröhling S, Fassnacht M, Mai K, and Kroiss M
- Subjects
- Humans, Nivolumab therapeutic use, Retrospective Studies, B7-H1 Antigen therapeutic use, Immunotherapy adverse effects, Immunotherapy methods, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy, Adrenocortical Carcinoma drug therapy, Antineoplastic Agents, Immunological adverse effects, Adrenal Cortex Neoplasms drug therapy
- Abstract
Objective: Clinical trials with immune checkpoint inhibitors (ICI) in adrenocortical carcinoma (ACC) have yielded contradictory results. We aimed to evaluate treatment response and safety of ICI in ACC in a real-life setting., Design: Retrospective cohort study of 54 patients with advanced ACC receiving ICI as compassionate use at 6 German reference centres between 2016 and 2022., Methods: Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAE) were assessed., Results: In 52 patients surviving at least 4 weeks after initiation of ICI, ORR was 13.5% (6-26) and DCR was 24% (16-41). PFS was 3.0 months (95% CI, 2.3-3.7). In all patients, median OS was 10.4 months (3.8-17). 17 TRAE occurred in 15 patients, which was associated with a longer PFS of 5.5 (1.9-9.2) vs 2.5 (2.0-3.0) months (HR 0.29, 95% CI, 0.13-0.66, P = 0.001) and OS of 28.2 (9.5-46.8) vs 7.0 (4.1-10.2) months (HR 0.34, 95% CI, 0.12-0.93). Positive tissue staining for programmed cell death ligand 1 (PD-L1) was associated with a longer PFS of 3.2 (2.6-3.8) vs 2.3 (1.6-3.0, P < 0.05) months. Adjusted for concomitant mitotane use, treatment with nivolumab was associated with lower risk of progression (HR 0.36, 0.15-0.90) and death (HR 0.20, 0.06-0.72) compared to pembrolizumab., Conclusions: In the real-life setting, we observe a response comparable to other second-line therapies and an acceptable safety profile in ACC patients receiving different ICI. The relevance of PD-L1 as a marker of response and the potentially more favourable outcome in nivolumab-treated patients require confirmation., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2023
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22. APOBEC3B protein expression and mRNA analyses in patients with high-grade serous ovarian carcinoma.
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Rüder U, Denkert C, Kunze CA, Jank P, Lindner J, Jöhrens K, Kulbe H, Sehouli J, Dietel M, Braicu E, and Darb-Esfahani S
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- Aged, Biomarkers, Tumor analysis, Cystadenocarcinoma, Serous immunology, Cystadenocarcinoma, Serous mortality, Disease-Free Survival, Female, Humans, Kaplan-Meier Estimate, Lymphocytes, Tumor-Infiltrating immunology, Middle Aged, Ovarian Neoplasms immunology, Ovarian Neoplasms mortality, RNA, Messenger analysis, Cystadenocarcinoma, Serous metabolism, Cytidine Deaminase biosynthesis, Minor Histocompatibility Antigens biosynthesis, Ovarian Neoplasms metabolism
- Abstract
APOBEC3 enzymes are part of the innate immune system and they are important in retroviral defense. The number of mutations in ovarian cancer increases with rising levels of APOBEC3B mRNA. We could confirm that APOBEC3B mRNA is upregulated in ovarian cancer cell lines and in ovarian cancer tissue. We evaluated APOBEC3B expression in histologically defined subtypes of ovarian cancer to identify its influence on overall survival (OS) and progression-free survival (PFS). Tissue microarrays from 219 patients with high-grade serous (HGSC), 61 with low-grade serous (LGSC), 62 with endometrioid (EC) and 55 with clear cell (CCC) ovarian carcinoma were stained using an antibody against APOBEC3B. Real-time quantitative PCR was performed to detect APOBEC3B mRNA levels in 274 cases of HGSC, in 11 cases of LGSC, in 47 cases of EC and in 29 cases of CCC. Tumor-infiltrating lymphocytes (TILs) have been evaluated in a previous project. APOBEC3B staining was cytoplasmic as well as nuclear and both were positively correlated (P<0.001). In HGSC a trend was detectable for positive cytoplasmic staining as favorable regarding OS (P=0.283) and PFS (P=0.137). High levels of APOBEC3B mRNA were associated with prolonged PFS in HGSC in univariate analyses (P=0.043) and multivariate analyses (HR 0.55; 95%CI 0.35-0.88; P=0.012). APOBEC3B cytoplasmic staining and APOBEC3B mRNA were positively correlated with TILs. APOBEC3B in HGSC is related to an active immune infiltrate. However, there is no evidence for APOBEC3B as a clinically relevant prognostic biomarker.
- Published
- 2019
- Full Text
- View/download PDF
23. Prognostic impact of programmed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor-infiltrating lymphocytes in ovarian high grade serous carcinoma.
- Author
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Darb-Esfahani S, Kunze CA, Kulbe H, Sehouli J, Wienert S, Lindner J, Budczies J, Bockmayr M, Dietel M, Denkert C, Braicu I, and Jöhrens K
- Subjects
- B7-H1 Antigen genetics, Biomarkers, Tumor genetics, Carcinoma genetics, Carcinoma immunology, Carcinoma therapy, Databases, Genetic, Disease-Free Survival, Female, Gene Expression Regulation, Neoplastic, Humans, Immunohistochemistry, Kaplan-Meier Estimate, Lymphocytes, Tumor-Infiltrating immunology, Lymphocytes, Tumor-Infiltrating pathology, Middle Aged, Neoplasm Grading, Neoplasms, Cystic, Mucinous, and Serous genetics, Neoplasms, Cystic, Mucinous, and Serous immunology, Neoplasms, Cystic, Mucinous, and Serous therapy, Ovarian Neoplasms genetics, Ovarian Neoplasms immunology, Ovarian Neoplasms therapy, Programmed Cell Death 1 Receptor genetics, RNA, Messenger genetics, Reverse Transcriptase Polymerase Chain Reaction, Time Factors, Tissue Array Analysis, B7-H1 Antigen analysis, Biomarkers, Tumor analysis, Carcinoma chemistry, Lymphocytes, Tumor-Infiltrating chemistry, Neoplasms, Cystic, Mucinous, and Serous chemistry, Ovarian Neoplasms chemistry, Programmed Cell Death 1 Receptor analysis
- Abstract
Aims: Antibodies targeting the checkpoint molecules programmed cell death 1 (PD-1) and its ligand PD-L1 are emerging cancer therapeutics. We systematically investigated PD-1 and PD-L1 expression patterns in the poor-prognosis tumor entity high-grade serous ovarian carcinoma., Methods: PD-1 and PD-L1 protein expression was determined by immunohistochemistry on tissue microarrays from 215 primary cancers both in cancer cells and in tumor-infiltrating lymphocytes (TILs). mRNA expression was measured by quantitative reverse transcription PCR. An in silico validation of mRNA data was performed in The Cancer Genome Atlas (TCGA) dataset., Results: PD-1 and PD-L1 expression in cancer cells, CD3+, PD-1+, and PD-L1+ TILs densities as well as PD-1 and PD-L1 mRNA levels were positive prognostic factors for progression-free (PFS) and overall survival (OS), with all factors being significant for PFS (p < 0.035 each), and most being significant for OS. Most factors also had prognostic value that was independent from age, stage, and residual tumor. Moreover, high PD-1+ TILs as well as PD-L1+ TILs densities added prognostic value to CD3+TILs (PD-1+: p = 0.002,; PD-L1+: p = 0.002). The significant positive prognostic impact of PD-1 and PD-L1 mRNA expression could be reproduced in the TCGA gene expression datasets (p = 0.02 and p < 0.0001, respectively)., Conclusions: Despite their reported immune-modulatory function, high PD-1 and PD-L1 levels are indicators of a favorable prognosis in ovarian cancer. Our data indicate that PD-1 and PD-L1 molecules are biologically relevant regulators of the immune response in high-grade serous ovarian carcinoma, which is an argument for the evaluation of immune checkpoint inhibiting drugs in this tumor entity.
- Published
- 2016
- Full Text
- View/download PDF
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