Search

Your search keyword '"Annette, Staebler"' showing total 237 results
Start Over Author "Annette, Staebler"
237 results on '"Annette, Staebler"'

1. Breast cancer patient-derived microtumors resemble tumor heterogeneity and enable protein-based stratification and functional validation of individualized drug treatment

Author

Nicole Anderle, Felix Schäfer-Ruoff, Annette Staebler, Nicolas Kersten, André Koch, Cansu Önder, Anna-Lena Keller, Simone Liebscher, Andreas Hartkopf, Markus Hahn, Markus Templin, Sara Y. Brucker, Katja Schenke-Layland, and Christian Schmees

Subjects
Preclinical tumor model, Tumor heterogeneity, Therapy resistance, Therapy sensitivity, Protein profiling, Breast cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Despite tremendous progress in deciphering breast cancer at the genomic level, the pronounced intra- and intertumoral heterogeneity remains a major obstacle to the advancement of novel and more effective treatment approaches. Frequent treatment failure and the development of treatment resistance highlight the need for patient-derived tumor models that reflect the individual tumors of breast cancer patients and allow a comprehensive analyses and parallel functional validation of individualized and therapeutically targetable vulnerabilities in protein signal transduction pathways. Here, we introduce the generation and application of breast cancer patient-derived 3D microtumors (BC-PDMs). Residual fresh tumor tissue specimens were collected from n = 102 patients diagnosed with breast cancer and subjected to BC-PDM isolation. BC-PDMs retained histopathological characteristics, and extracellular matrix (ECM) components together with key protein signaling pathway signatures of the corresponding primary tumor tissue. Accordingly, BC-PDMs reflect the inter- and intratumoral heterogeneity of breast cancer and its key signal transduction properties. DigiWest®-based protein expression profiling of identified treatment responder and non-responder BC-PDMs enabled the identification of potential resistance and sensitivity markers of individual drug treatments, including markers previously associated with treatment response and yet undescribed proteins. The combination of individualized drug testing with comprehensive protein profiling analyses of BC-PDMs may provide a valuable complement for personalized treatment stratification and response prediction for breast cancer.

Published
2023
Full Text
View/download PDF

2. Image‐guided metabolomics and transcriptomics reveal tumour heterogeneity in luminal A and B human breast cancer beyond glucose tracer uptake

Author

Qianlu Yang, Sisi Deng, Heike Preibsch, Tim‐Colin Schade, André Koch, Georgy Berezhnoy, Laimdota Zizmare, Anna Fischer, Brigitte Gückel, Annette Staebler, Andreas D. Hartkopf, Bernd J. Pichler, Christian laFougère, Markus Hahn, Irina Bonzheim, Konstantin Nikolaou, and Christoph Trautwein

Subjects
[18F]FDG, 1H‐NMR, gene expression, PET/MR, tumour microenvironment, multi‐omics, Medicine (General), R5-920
Abstract

Abstract Background Breast cancer is a metabolically heterogeneous disease, and although the concept of heterogeneous cancer metabolism is known, its precise role in human breast cancer is yet to be fully elucidated. Methods We investigated in an explorative approach a cohort of 42 primary mamma carcinoma patients with positron emission tomography/magnetic resonance imaging (PET/MR) prior to surgery, followed by histopathology and molecular diagnosis. From a subset of patients, which showed high metabolic heterogeneity based on tracer uptake and pathology classification, tumour centre and periphery specimen tissue samples were further investigated by a targeted breast cancer gene expression panel and quantitative metabolomics by nuclear magnetic resonance (NMR) spectroscopy. All data were analysed in a combinatory approach. Results [18F]FDG (2‐deoxy‐2‐[fluorine‐18]fluoro‐d‐glucose) tracer uptake confirmed dominance of glucose metabolism in the breast tumour centre, with lower levels in the periphery. Additionally, we observed differences in lipid and proliferation related genes between luminal A and B subtypes in the centre and periphery. Tumour periphery showed elevated acetate levels and enrichment in lipid metabolic pathways genes especially in luminal B. Furthermore, serine was increased in the periphery and higher expression of thymidylate synthase (TYMS) indicated one‐carbon metabolism increased in tumour periphery. The overall metabolic activity based on [18F]FDG uptake of luminal B subtype was higher than that of luminal A and the difference between the periphery and centre increased with tumour grade. Conclusion Our analysis indicates variations in metabolism among different breast cancer subtypes and sampling locations which details the heterogeneity of the breast tumours. Correlation analysis of [18F]FDG tracer uptake, transcriptome and tumour metabolites like acetate and serine facilitate the search for new candidates for metabolic tracers and permit distinguishing luminal A and B. This knowledge may help to differentiate subtypes preclinically or to provide patients guide for neoadjuvant therapy and optimised surgical protocols based on individual tumour metabolism.

Published
2024
Full Text
View/download PDF

3. p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study

Author

Martin Köbel, Eun‐Young Kang, Ashley Weir, Peter F Rambau, Cheng‐Han Lee, Gregg S Nelson, Prafull Ghatage, Nicola S Meagher, Marjorie J Riggan, Jennifer Alsop, Michael S Anglesio, Matthias W Beckmann, Christiani Bisinotto, Michelle Boisen, Jessica Boros, Alison H Brand, Angela Brooks‐Wilson, Michael E Carney, Penny Coulson, Madeleine Courtney‐Brooks, Kara L Cushing‐Haugen, Cezary Cybulski, Suha Deen, Mona A El‐Bahrawy, Esther Elishaev, Ramona Erber, Sian Fereday, AOCS Group, Anna Fischer, Simon A Gayther, Arantzazu Barquin‐Garcia, Aleksandra Gentry‐Maharaj, C Blake Gilks, Helena Gronwald, Marcel Grube, Paul R Harnett, Holly R Harris, Andreas D Hartkopf, Arndt Hartmann, Alexander Hein, Joy Hendley, Brenda Y Hernandez, Yajue Huang, Anna Jakubowska, Mercedes Jimenez‐Linan, Michael E Jones, Catherine J Kennedy, Tomasz Kluz, Jennifer M Koziak, Jaime Lesnock, Jenny Lester, Jan Lubiński, Teri A Longacre, Maria Lycke, Constantina Mateoiu, Bryan M McCauley, Valerie McGuire, Britta Ney, Alexander Olawaiye, Sandra Orsulic, Ana Osorio, Luis Paz‐Ares, Teresa Ramón y Cajal, Joseph H Rothstein, Matthias Ruebner, Minouk J Schoemaker, Mitul Shah, Raghwa Sharma, Mark E Sherman, Yurii B Shvetsov, Naveena Singh, Helen Steed, Sarah J Storr, Aline Talhouk, Nadia Traficante, Chen Wang, Alice S Whittemore, Martin Widschwendter, Lynne R Wilkens, Stacey J Winham, Javier Benitez, Andrew Berchuck, David D Bowtell, Francisco J Candido dos Reis, Ian Campbell, Linda S Cook, Anna DeFazio, Jennifer A Doherty, Peter A Fasching, Renée T Fortner, María J García, Marc T Goodman, Ellen L Goode, Jacek Gronwald, David G Huntsman, Beth Y Karlan, Linda E Kelemen, Stefan Kommoss, Nhu D Le, Stewart G Martin, Usha Menon, Francesmary Modugno, Paul DP Pharoah, Joellen M Schildkraut, Weiva Sieh, Annette Staebler, Karin Sundfeldt, Anthony J Swerdlow, Susan J Ramus, and James D Brenton

Subjects
ovarian cancer, high‐grade serous carcinoma, endometrioid, clear cell, TP53, p53, Pathology, RB1-214
Abstract

Abstract Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high‐grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi‐institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36–3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11–2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.

Published
2023
Full Text
View/download PDF

4. Tissue-preserving treatment with non-invasive physical plasma of cervical intraepithelial neoplasia—a prospective controlled clinical trial

Author

Martin Weiss, Marcel Arnholdt, Anna Hißnauer, Irma Fischer, Birgitt Schönfisch, Jürgen Andress, Sophia Gerstner, Dominik Dannehl, Hans Bösmüller, Annette Staebler, Sara Y. Brucker, and Melanie Henes

Subjects
neoplasia, cervical intra epithelial neoplasia, physical plasma, non-invasive treatments, cervical cancer prevention, Medicine (General), R5-920
Abstract

ObjectiveCervical cancer represents the fourth leading cause of cancer among women and is associated with over 311,000 annual deaths worldwide. Timely diagnosis is crucial given the lengthy pre-cancerous phase, which is typified by cervical intraepithelial neoplastic lesions. However, current treatment methods are often tissue-destructive and can be accompanied by severe side effects. To address these concerns, our study introduces a novel, gentle approach for the tissue-preserving treatment of CIN lesions.ResultsWe present findings of a controlled, prospective, single-armed phase IIb clinical trial performed at the Department for Women’s Health, Tübingen, Germany. From September 2017 to March 2022 we assessed 570 participants for study eligibility. Of the screened patients, 63 participants met with CIN1/2 lesions met the inclusion criteria and were treated with non-invasive physical plasma (NIPP). Assessment of treatment efficacy was based on a comprehensive analysis of histological and cytological findings, along with high-risk HPV infection load at 3 and 6 months post-treatment. Comparative analyses were performed retrospectively with data obtained from 287 untreated patients in the control group. Our findings indicate that patients treated with NIPP experienced an 86.2% rate of full remission, along with a 3.4% rate of partial remission of CIN lesions, which compares favorably to the control group’s rates of 40.4% and 4.5%, respectively. Additionally, we observed a twofold reduction in high-risk HPV infections following NIPP treatment. Minor side effects were observed, such as mild pain during treatment and short-term smear bleeding or increased vaginal discharge within 24 h after treatment. Given the experimental nature of NIPP treatment and the availability of established standard treatments, our study was designed as a non-randomized study.ConclusionNIPP treatment offers a highly flexible and easy-to-apply method for treating pre-cancerous CIN1/2 lesions. This non-invasive approach is notable for its tissue-preserving nature, making it a promising alternative to current excisional and ablative treatments. CIN1/2 lesions were employed as preliminary in vivo models for the targeted treatment of CIN3 lesions.Clinical trial registrationhttps://www.clinicaltrials.gov, identifier NCT03218436.

Published
2023
Full Text
View/download PDF

5. Optical Emission Spectroscopy for the Real-Time Identification of Malignant Breast Tissue

Author

Selin Guergan, Bettina Boeer, Regina Fugunt, Gisela Helms, Carmen Roehm, Anna Solomianik, Alexander Neugebauer, Daniela Nuessle, Mirjam Schuermann, Kristin Brunecker, Ovidiu Jurjut, Karen A. Boehme, Sascha Dammeier, Markus D. Enderle, Sabrina Bettio, Irene Gonzalez-Menendez, Annette Staebler, Sara Y. Brucker, Bernhard Kraemer, Diethelm Wallwiener, Falko Fend, and Markus Hahn

Subjects
optical emission spectroscopy, breast cancer, tumor tissue, tumor margin, machine learning, support vector machine, Medicine (General), R5-920
Abstract

Breast conserving resection with free margins is the gold standard treatment for early breast cancer recommended by guidelines worldwide. Therefore, reliable discrimination between normal and malignant tissue at the resection margins is essential. In this study, normal and abnormal tissue samples from breast cancer patients were characterized ex vivo by optical emission spectroscopy (OES) based on ionized atoms and molecules generated during electrosurgical treatment. The aim of the study was to determine spectroscopic features which are typical for healthy and neoplastic breast tissue allowing for future real-time tissue differentiation and margin assessment during breast cancer surgery. A total of 972 spectra generated by electrosurgical sparking on normal and abnormal tissue were used for support vector classifier (SVC) training. Specific spectroscopic features were selected for the classification of tissues in the included breast cancer patients. The average classification accuracy for all patients was 96.9%. Normal and abnormal breast tissue could be differentiated with a mean sensitivity of 94.8%, a specificity of 99.0%, a positive predictive value (PPV) of 99.1% and a negative predictive value (NPV) of 96.1%. For 66.6% patients all classifications reached 100%. Based on this convincing data, a future clinical application of OES-based tissue differentiation in breast cancer surgery seems to be feasible.

Published
2024
Full Text
View/download PDF

6. Adult‐type granulosa cell tumor of the ovary: a FOXL2‐centric disease

Author

Jessica A Pilsworth, Dawn R Cochrane, Samantha J Neilson, Bahar H Moussavi, Daniel Lai, Aslı D Munzur, Janine Senz, Yi Kan Wang, Sina Zareian, Ali Bashashati, Adele Wong, Jacqueline Keul, Annette Staebler, Hannah S vanMeurs, Hugo M Horlings, Stefan Kommoss, Friedrich Kommoss, Esther Oliva, Anniina EM Färkkilä, Blake Gilks, and David G Huntsman

Subjects
adult‐type granulosa cell tumor of the ovary, FOXL2, TERT promoter, KMT2D, targeted sequencing, mutation profiling, Pathology, RB1-214
Abstract

Abstract Adult‐type granulosa cell tumors (aGCTs) account for 90% of malignant ovarian sex cord‐stromal tumors and 2–5% of all ovarian cancers. These tumors are usually diagnosed at an early stage and are treated with surgery. However, one‐third of patients relapse between 4 and 8 years after initial diagnosis, and there are currently no effective treatments other than surgery for these relapsed patients. As the majority of aGCTs (>95%) harbor a somatic mutation in FOXL2 (c.C402G; p.C134W), the aim of this study was to identify genetic mutations besides FOXL2 C402G in aGCTs that could explain the clinical diversity of this disease. Whole‐genome sequencing of 10 aGCTs and their matched normal blood was performed to identify somatic mutations. From this analysis, a custom amplicon‐based panel was designed to sequence 39 genes of interest in a validation cohort of 83 aGCTs collected internationally. KMT2D inactivating mutations were present in 10 of 93 aGCTs (10.8%), and the frequency of these mutations was similar between primary and recurrent aGCTs. Inactivating mutations, including a splice site mutation in candidate tumor suppressor WNK2 and nonsense mutations in PIK3R1 and NLRC5, were identified at a low frequency in our cohort. Missense mutations were identified in cell cycle‐related genes TP53, CDKN2D, and CDK1. From these data, we conclude that aGCTs are comparatively a homogeneous group of tumors that arise from a limited set of genetic events and are characterized by the FOXL2 C402G mutation. Secondary mutations occur in a subset of patients but do not explain the diverse clinical behavior of this disease. As the FOXL2 C402G mutation remains the main driver of this disease, progress in the development of therapeutics for aGCT would likely come from understanding the functional consequences of the FOXL2 C402G mutation.

Published
2021
Full Text
View/download PDF

7. Detection of circulating cell-free HPV DNA of 13 HPV types for patients with cervical cancer as potential biomarker to monitor therapy response and to detect relapse

Author

Suzana Mittelstadt, Olga Kelemen, Jakob Admard, Axel Gschwind, André Koch, Sarah Wörz, Ernst Oberlechner, Tobias Engler, Irina Bonzheim, Annette Staebler, Nicola Weidner, Frank Stubenrauch, Thomas Iftner, Olaf Riess, Christopher Schroeder, Stefan Kommoss, and Stephan Ossowski

Subjects
Cancer Research, Oncology
Abstract

Background HPV-related cervical cancer (CC) is the fourth most frequent cancer in women worldwide. Cell-free tumour DNA is a potent biomarker to detect treatment response, residual disease, and relapse. We investigated the potential use of cell-free circulating HPV-DNA (cfHPV-DNA) in plasma of patients with CC. Methods cfHPV-DNA levels were measured using a highly sensitive next-generation sequencing-based approach targeting a panel of 13 high-risk HPV types. Results Sequencing was performed in 69 blood samples collected from 35 patients, of which 26 were treatment-naive when the first liquid biopsy sample was retrieved. cfHPV-DNA was successfully detected in 22/26 (85%) cases. A significant correlation between tumour burden and cfHPV-DNA levels was observed: cfHPV-DNA was detectable in all treatment-naive patients with advanced-stage disease (17/17, FIGO IB3–IVB) and in 5/9 patients with early-stage disease (FIGO IA–IB2). Sequential samples revealed a decrease of cfHPV-DNA levels in 7 patients corresponding treatment response and an increase in a patient with relapse. Conclusions In this proof-of-concept study we demonstrated the potential of cfHPV-DNA as a biomarker for therapy monitoring in patients with primary and recurrent CC. Our findings facilitate the development of a sensitive and precise, non-invasive, inexpensive, and easily accessible tool in CC diagnosis, therapy monitoring and follow-up.

Published
2023

8. CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma

Author

Eun-Young, Kang, Ashley, Weir, Nicola S, Meagher, Kyo, Farrington, Gregg S, Nelson, Prafull, Ghatage, Cheng-Han, Lee, Marjorie J, Riggan, Adelyn, Bolithon, Gordana, Popovic, Betty, Leung, Katrina, Tang, Neil, Lambie, Joshua, Millstein, Jennifer, Alsop, Michael S, Anglesio, Beyhan, Ataseven, Ellen, Barlow, Matthias W, Beckmann, Jessica, Berger, Christiani, Bisinotto, Hans, Bösmüller, Jessica, Boros, Alison H, Brand, Angela, Brooks-Wilson, Sara Y, Brucker, Michael E, Carney, Yovanni, Casablanca, Alicia, Cazorla-Jiménez, Paul A, Cohen, Thomas P, Conrads, Linda S, Cook, Penny, Coulson, Madeleine, Courtney-Brooks, Daniel W, Cramer, Philip, Crowe, Julie M, Cunningham, Cezary, Cybulski, Kathleen M, Darcy, Mona A, El-Bahrawy, Esther, Elishaev, Ramona, Erber, Rhonda, Farrell, Sian, Fereday, Anna, Fischer, María J, García, Simon A, Gayther, Aleksandra, Gentry-Maharaj, C Blake, Gilks, Marcel, Grube, Paul R, Harnett, Shariska Petersen, Harrington, Philipp, Harter, Arndt, Hartmann, Jonathan L, Hecht, Sebastian, Heikaus, Alexander, Hein, Florian, Heitz, Joy, Hendley, Brenda Y, Hernandez, Susanna Hernando, Polo, Sabine, Heublein, Akira, Hirasawa, Estrid, Høgdall, Claus K, Høgdall, Hugo M, Horlings, David G, Huntsman, Tomasz, Huzarski, Andrea, Jewell, Mercedes, Jimenez-Linan, Michael E, Jones, Scott H, Kaufmann, Catherine J, Kennedy, Dineo, Khabele, Felix K F, Kommoss, Roy F P M, Kruitwagen, Diether, Lambrechts, Nhu D, Le, Marcin, Lener, Jenny, Lester, Yee, Leung, Anna, Linder, Liselore, Loverix, Jan, Lubiński, Rashna, Madan, G Larry, Maxwell, Francesmary, Modugno, Susan L, Neuhausen, Alexander, Olawaiye, Siel, Olbrecht, Sandra, Orsulic, José, Palacios, Celeste Leigh, Pearce, Malcolm C, Pike, Carmel M, Quinn, Ganendra Raj, Mohan, Cristina, Rodríguez-Antona, Matthias, Ruebner, Andy, Ryan, Stuart G, Salfinger, Naoko, Sasamoto, Joellen M, Schildkraut, Minouk J, Schoemaker, Mitul, Shah, Raghwa, Sharma, Yurii B, Shvetsov, Naveena, Singh, Gabe S, Sonke, Linda, Steele, Colin J R, Stewart, Karin, Sundfeldt, Anthony J, Swerdlow, Aline, Talhouk, Adeline, Tan, Sarah E, Taylor, Kathryn L, Terry, Aleksandra, Tołoczko, Nadia, Traficante, Koen K, Van de Vijver, Maaike A, van der Aa, Toon, Van Gorp, Els, Van Nieuwenhuysen, Lilian, van-Wagensveld, Ignace, Vergote, Robert A, Vierkant, Chen, Wang, Lynne R, Wilkens, Stacey J, Winham, Anna H, Wu, Javier, Benitez, Andrew, Berchuck, Francisco J, Candido Dos Reis, Anna, DeFazio, Peter A, Fasching, Ellen L, Goode, Marc T, Goodman, Jacek, Gronwald, Beth Y, Karlan, Stefan, Kommoss, Usha, Menon, Hans-Peter, Sinn, Annette, Staebler, James D, Brenton, David D, Bowtell, Paul D P, Pharoah, Susan J, Ramus, Martin, Köbel, MUMC+: MA Obstetrie Gynaecologie (3), MUMC+: Vrouw Moeder en Kind Centrum (3), Obstetrie & Gynaecologie, MUMC+: MA Arts Assistenten Obstetrie Gynaecologie (6), RS: GROW - R2 - Basic and Translational Cancer Biology, and AOCS Group

Subjects
Cancer Research, ovarian cancer, Oncology, high-grade serous carcinoma, Human medicine, prognosis, CCNE1 amplification, cyclin E1 expression
Abstract

BACKGROUND: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. METHODS: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. RESULTS: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. CONCLUSION: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC. ispartof: CANCER vol:129 issue:5 pages:697-713 ispartof: location:United States status: published

Published
2023

9. L1-CAM in Mucinous Ovarian Carcinomas and Borderline Tumors

Author

Rebekka Wiedenhoefer, Elisa Schmoeckel, Marcel Grube, Mihály Sulyok, Iana Pasternak, Christine Beschorner, Karen Greif, Sara Brucker, Doris Mayr, Stefan Kommoss, Falko Fend, Annette Staebler, and Anna K. Fischer

Subjects
Surgery, Anatomy, Pathology and Forensic Medicine
Published
2023

10. Homologous Recombination Deficiency as an Ovarian Cancer Biomarker in a Real-World Cohort

Author

Carsten Denkert, Marcel Romey, Brad Swedlund, Akira Hattesohl, Julia Teply-Szymanski, Stefan Kommoss, Kristin Kaiser, Annette Staebler, Andreas du Bois, Albert Grass, Christiane Knappmeyer, Florian Heitz, Cara Solimeno, Thomas Ebel, Philipp Harter, Frederik Marmé, Paul Jank, Timo Gaiser, Chris Neff, Uwe Wagner, Kirsten M. Timms, and Fiona Rodepeter

Subjects
Molecular Medicine, Pathology and Forensic Medicine
Published
2022

11. Dataset on patients with Recurrent Borderline Ovarian Tumors and Table with Review of Literature on Fertility and Oncologic Outcomes of patients with Borderline Ovarian Tumors

Author

Helmut Plett, MD, Enzo Ricciardi, MD, PhD, Philipp Harter, MD, PhD, Beyhan Ataseven, MD, PhD, Florian Heitz, MD, Sonia Prader, MD, Stephanie Schneider, MD, Sebastian Heikaus, MD, PhD, Annette Fisseler-Eckhoff, MD, PhD, Friedrich Kommoss, MD, PhD, Sigurd F. Lax, MD, PhD, Annette Staebler, MD, PhD, Alexander Traut, and Andreas du Bois, MD, PhD

Subjects
Borderline tumors of the ovary, Fertility sparing surgery, Radical surgery, Recurrence, Conservative treatment, Invasive Recurrence, Computer applications to medicine. Medical informatics, R858-859.7, Science (General), Q1-390
Abstract

The data presented here is related to the research article entitled “FERTILITY-SPARING SURGERY AND REPRODUCTIVE-OUTCOMES IN PATIENTS WITH BORDERLINE OVARIAN TUMORS” by Plett et al. in Journal of Gynecologic Oncology [1] and is analysed and discussed in detail. 18 Patients with Recurrent Borderline Ovarian Tumors (BOT) were identified and listed in Table 1. All patients underwent treatment for primary BOT either per radical surgery (RS) or fertility sparing surgery (FSS) by the same team in Horst Schmidt Klinik (HSK) in Wiesbaden and the Department of Gynecology and Gynecologic Oncology at Kliniken Essen-Mitte between January 2000 and December 2018 and were followed up closely. Details on patients` and surgical characteristics are given as well as management of character of recurrent disease. In Table 2 important publications from the last 20 years are listed in order to visualize better the oncologic outcomes (invasive and non-invasive relapses) and calculated risks of recurrence with the purpose to understand better the important findings of the related article cited above.

Published
2020
Full Text
View/download PDF

12. Increased FOXJ1 protein expression is associated with improved overall survival in high-grade serous ovarian carcinoma: an Ovarian Tumor Tissue Analysis Consortium Study

Author

Ashley, Weir, Eun-Young, Kang, Nicola S, Meagher, Gregg S, Nelson, Prafull, Ghatage, Cheng-Han, Lee, Marjorie J, Riggan, Aleksandra, Gentry-Maharaj, Andy, Ryan, Naveena, Singh, Martin, Widschwendter, Jennifer, Alsop, Michael S, Anglesio, Matthias W, Beckmann, Jessica, Berger, Christiani, Bisinotto, Jessica, Boros, Alison H, Brand, James D, Brenton, Angela, Brooks-Wilson, Michael E, Carney, Julie M, Cunningham, Kara L, Cushing-Haugen, Cezary, Cybulski, Esther, Elishaev, Ramona, Erber, Sian, Fereday, Anna, Fischer, Luis, Paz-Ares, Javier, Gayarre, Blake C, Gilks, Marcel, Grube, Paul R, Harnett, Holly R, Harris, Arndt, Hartmann, Alexander, Hein, Joy, Hendley, Brenda Y, Hernandez, Sabine, Heublein, Yajue, Huang, Tomasz, Huzarski, Anna, Jakubowska, Mercedes, Jimenez-Linan, Catherine J, Kennedy, Felix K F, Kommoss, Jennifer M, Koziak, Bernhard, Kraemer, Nhu D, Le, Jaime, Lesnock, Jenny, Lester, Jan, Lubiński, Janusz, Menkiszak, Britta, Ney, Alexander, Olawaiye, Sandra, Orsulic, Ana, Osorio, Luis, Robles-Díaz, Matthias, Ruebner, Mitul, Shah, Raghwa, Sharma, Yurii B, Shvetsov, Helen, Steed, Aline, Talhouk, Sarah E, Taylor, Nadia, Traficante, Robert A, Vierkant, Chen, Wang, Lynne R, Wilkens, Stacey J, Winham, Javier, Benitez, Andrew, Berchuck, David D, Bowtell, Francisco J, Candido Dos Reis, Linda S, Cook, Anna, DeFazio, Jennifer A, Doherty, Peter A, Fasching, María J, García, Ellen L, Goode, Marc T, Goodman, Jacek, Gronwald, David G, Huntsman, Beth Y, Karlan, Stefan, Kommoss, Francesmary, Modugno, Joellen M, Schildkraut, Hans-Peter, Sinn, Annette, Staebler, Linda E, Kelemen, Caroline E, Ford, Usha, Menon, Paul D P, Pharoah, Martin, Köbel, and R, Sharma

Subjects
Cancer Research, Oncology
Abstract

Background Recently, we showed a >60% difference in 5-year survival for patients with tubo-ovarian high-grade serous carcinoma (HGSC) when stratified by a 101-gene mRNA expression prognostic signature. Given the varied patient outcomes, this study aimed to translate prognostic mRNA markers into protein expression assays by immunohistochemistry and validate their survival association in HGSC. Methods Two prognostic genes, FOXJ1 and GMNN, were selected based on high-quality antibodies, correlation with protein expression and variation in immunohistochemical scores in a preliminary cohort (n = 134 and n = 80, respectively). Six thousand four hundred and thirty-four (FOXJ1) and 5470 (GMNN) formalin-fixed, paraffin-embedded ovarian neoplasms (4634 and 4185 HGSC, respectively) represented on tissue microarrays from the Ovarian Tumor Tissue Analysis consortium underwent immunohistochemical staining and scoring, then univariate and multivariate survival analysis. Results Consistent with mRNA, FOXJ1 protein expression exhibited a linear, increasing association with improved overall survival in HGSC patients. Women with >50% expression had the most favourable outcomes (HR = 0.78, 95% CI 0.67–0.91, p 35% GMNN expression showed a trend for better outcomes, though this was not significant. Conclusion We provide foundational evidence for the prognostic value of FOXJ1 in HGSC, validating the prior mRNA-based prognostic association by immunohistochemistry.

Published
2022

13. Gene-Expression Profiling of Mucinous Ovarian Tumors and Comparison with Upper and Lower Gastrointestinal Tumors Identifies Markers Associated with Adverse Outcomes

Author

Nicola S, Meagher, Kylie L, Gorringe, Matthew, Wakefield, Adelyn, Bolithon, Chi Nam Ignatius, Pang, Derek S, Chiu, Michael S, Anglesio, Kylie-Ann, Mallitt, Jennifer A, Doherty, Holly R, Harris, Joellen M, Schildkraut, Andrew, Berchuck, Kara L, Cushing-Haugen, Ksenia, Chezar, Angela, Chou, Adeline, Tan, Jennifer, Alsop, Ellen, Barlow, Matthias W, Beckmann, Jessica, Boros, David D L, Bowtell, Alison H, Brand, James D, Brenton, Ian, Campbell, Dane, Cheasley, Joshua, Cohen, Cezary, Cybulski, Esther, Elishaev, Ramona, Erber, Rhonda, Farrell, Anna, Fischer, Zhuxuan, Fu, Blake, Gilks, Anthony J, Gill, Charlie, Gourley, Marcel, Grube, Paul R, Harnett, Arndt, Hartmann, Anusha, Hettiaratchi, Claus K, Høgdall, Tomasz, Huzarski, Anna, Jakubowska, Mercedes, Jimenez-Linan, Catherine J, Kennedy, Byoung-Gie, Kim, Jae-Weon, Kim, Jae-Hoon, Kim, Kayla, Klett, Jennifer M, Koziak, Tiffany, Lai, Angela, Laslavic, Jenny, Lester, Yee, Leung, Na, Li, Winston, Liauw, Belle W X, Lim, Anna, Linder, Jan, Lubiński, Sakshi, Mahale, Constantina, Mateoiu, Simone, McInerny, Janusz, Menkiszak, Parham, Minoo, Suzana, Mittelstadt, David, Morris, Sandra, Orsulic, Sang-Yoon, Park, Celeste Leigh, Pearce, John V, Pearson, Malcolm C, Pike, Carmel M, Quinn, Ganendra Raj, Mohan, Jianyu, Rao, Marjorie J, Riggan, Matthias, Ruebner, Stuart, Salfinger, Clare L, Scott, Mitul, Shah, Helen, Steed, Colin J R, Stewart, Deepak, Subramanian, Soseul, Sung, Katrina, Tang, Paul, Timpson, Robyn L, Ward, Rebekka, Wiedenhoefer, Heather, Thorne, Paul A, Cohen, Philip, Crowe, Peter A, Fasching, Jacek, Gronwald, Nicholas J, Hawkins, Estrid, Høgdall, David G, Huntsman, Paul A, James, Beth Y, Karlan, Linda E, Kelemen, Stefan, Kommoss, Gottfried E, Konecny, Francesmary, Modugno, Sue K, Park, Annette, Staebler, Karin, Sundfeldt, Anna H, Wu, Aline, Talhouk, Paul D P, Pharoah, Lyndal, Anderson, Anna, DeFazio, Martin, Köbel, Michael L, Friedlander, and Susan J, Ramus

Subjects
Ovarian Neoplasms, Cancer Research, BORDERLINE TUMORS, CARCINOMA, ADENOCARCINOMA, TRANSGELIN, Carcinoma, Ovarian Epithelial, EXPANSILE, Prognosis, INTESTINAL-TYPE, CANCER, Adenocarcinoma, Mucinous, PATTERN, RARE, Oncology, POOR-PROGNOSIS, Humans, Female, Neoplasm Staging, Gastrointestinal Neoplasms
Abstract

Purpose: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. Experimental Design: Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55). Results: Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04–7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04–1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01–1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). Conclusions: An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies.

Published
2022

14. Decidualization is Impaired in Endometrial Stromal Cells from Uterine Rudiments in Mayer-Rokitansky-Küster-Hauser Syndrome

Author

Sara Y. Brucker, Simone Eisenbeis, Juliana König, Melanie Lamy, Madhuri S. Salker, Ni Zeng, Harald Seeger, Melanie Henes, Dorit Schöller, Birgitt Schönfisch, Annette Staebler, Florin-Andrei Taran, Diethelm Wallwiener, and Katharina Rall

Subjects
Müllerian aplasia, Decidualization, Endometrium, Congenital vaginal agenesis, Müllerian agenesis, Physiology, QP1-981, Biochemistry, QD415-436
Abstract

Background/Aims: Uterine rudiments from patients with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) contain all tissues typically found in the uterus. Endometrium from the rudiments predominantly exhibits basalis-like features, and endometrial proliferative capacity in patients’ epithelium and stroma is significantly lower. Methods: This single-center, prospective study conducted at a major German university hospital compared in-vitro decidualization in cultured ESCs from MRKHS patients and hysterectomy controls. Primary ESC cultures were established from both sources. Hormone-induced prolactin and IGFBP-1 secretion served as a measure of their ability to undergo decidualization in response to hormonal stimulation. Expression levels of 8 key marker genes of decidualization were also determined. Results: At day 9, mean secretion of prolactin and IGFBP-1 was significantly reduced by 89.0% and 99.5%, respectively, in MRKHS ESCs vs. hysterectomy controls, both indicating impaired decidualization of MRKHS ESCs. Key decidual markers confirmed impaired decidualization in MRKHS patients. Conclusion: Our results indicate that the ESCs from MRKHS patients lack hormone responsiveness as a potential sign of dysfunctional hormone receptor function, which may also play a role in the onset of MRKHS. Further studies are needed to corroborate our findings, directly address receptor function, and elucidate the role of other potential determinants of uterine development and adult function.

Published
2017
Full Text
View/download PDF

16. Supplementary Data, Supplementary Tables 1, 3, and 4, Supplementary Figures 1-12 from EZH2 Loss Drives Resistance to Carboplatin and Paclitaxel in Serous Ovarian Cancers Expressing ATM

Author

Hans Neubauer, Markus F. Templin, Tanja Fehm, Dieter Niederacher, Ines Beyer, Diethelm Wallwiener, Sara Brucker, Andreas D. Hartkopf, Annette Staebler, Silvia Darb-Esfahani, Jalid Sehouli, Elena I. Braicu, Larissa Walter, Julia Gottstein, Martin Schlensog, Martina Rudelius, Ellen Honisch, Ruan van Rensburg, Yvonne Beiter, and Johanna Naskou

Abstract

Table S1: Clinical attributes of primary ovarian cancer patients used in this study. Table S3: Proteins and protein modifications detected in differential amounts in responsive and non-responsive ovarian cancers. Wilcoxon-Mann-Whitney Test; W = rank sum; RESP = responsive (DFS > 12 months); NRESP = non-responsive (DFS {less than or equal to} 12 months). Table S4: Gene variants (Variant), amino acid change (AA change) and allele frequencies of sequenced tumors from 17 patients (SXXX). Tumor content of tissues is listed at the end of the table. Figure S1: Screening of eight non-responsive and nine responsive tumor samples from ovarian cancer patients using DigiWest protein array analysis with 279 antibodies against proteins and their modifications (Wilcoxon-Mann-Whitney, p{less than or equal to}0.05). Figure S2: ATM/EZH2 protein ratios in 17 tumor samples with non-responders and responders quantified in the DigiWest analysis. Figure S3: Controls of immunohistochemistry staining. Figure S4: Correlation analysis of mean immunoreactive scores from stainings of EZH2 and ATM (left or phospho-Rb (Ser807/811) (right) in 34 ovarian cancer patients. n=2 per tumor sample Figure S5: A: Representative image of PLA analysis on tissue microarray spots. DAPI: staining of cell nuclei. FITC: Autofluorescence of tissue in FITC channel and determination of area for analysis (830 µm diameter). Cy5: Channel for PLA measurement after subtracting background signals of FITC channels. Analyzed: Automated counted spots of interactions. Bars represent 200 µm. B: Representative control (rabbit isotype) for PLA analysis on tissue microarray spots. C: Quantification of PLA interactions in an ovarian cancer tissue. Positive control: original PLA protocol using EZH2 and phospho-ATM (S1981) antibodies. Negative control: Staining procedure without primary antibodies. Isotype control rabbit: PLA protocol using rabbit isotype antibodies instead of antibodies against EZH2. Isotype control mouse: PLA protocol using mouse isotype antibodies instead of antibodies against phospho-ATM (S1981). n = 5. Figure S6: Correlation analysis of the mean IRS scores from stainings of ATM and mean PLA signals of EZH2 and ATM pS1981 in 34 samples on tissue microarrays; Spearman correlation; n=2 per tumor sample. Figure S7: Correlation analysis of mean IC50 values calculated in cell line cells. Values of paclitaxel mono-treatment were compared to the values of combinational treatment (CP scale). Figure S8: EZH2 protein levels in lysates of untreated cell lines analyzed with Spearman correlation against mean logIC50 values for CP (left) and TX (right); n=3. Grid line=linear regression line. Figure S9: ATM protein levels in lysates of untreated cell lines analyzed with Spearman correlation against mean logIC50 values for CP (left) and TX (right); n=3. Grid line=linear regression line. Figure S10: Hierarchical clustering of quantified total protein and protein modifications of cell cycle proteins measured with DigiWest technology. Figure S11: Proximity ligation assay on A2780 cells during treatment with CPTX using standard protocol (EZH2 + pATM) as positive control or isotype controls with mouse antibodies instead of pATM (mIgG1) or rabbit antibodies instead of EZH2 antibodies. Figure S12: Scheme suggesting a putative interaction of EZH2 and ATM during treatment with CPTX.

Published
2023

17. Supplementary Table S2 from EZH2 Loss Drives Resistance to Carboplatin and Paclitaxel in Serous Ovarian Cancers Expressing ATM

Author

Hans Neubauer, Markus F. Templin, Tanja Fehm, Dieter Niederacher, Ines Beyer, Diethelm Wallwiener, Sara Brucker, Andreas D. Hartkopf, Annette Staebler, Silvia Darb-Esfahani, Jalid Sehouli, Elena I. Braicu, Larissa Walter, Julia Gottstein, Martin Schlensog, Martina Rudelius, Ellen Honisch, Ruan van Rensburg, Yvonne Beiter, and Johanna Naskou

Abstract

Table S2.

Published
2023

18. Supplementary Methods 1 from Gene-Expression Profiling of Mucinous Ovarian Tumors and Comparison with Upper and Lower Gastrointestinal Tumors Identifies Markers Associated with Adverse Outcomes

Author

Susan J. Ramus, Michael L. Friedlander, Martin Köbel, Anna DeFazio, Lyndal Anderson, Paul D.P. Pharoah, Aline Talhouk, Anna H. Wu, Karin Sundfeldt, Annette Staebler, Sue K. Park, Francesmary Modugno, Gottfried E. Konecny, Stefan Kommoss, Linda E. Kelemen, Beth Y. Karlan, Paul A. James, David G. Huntsman, Estrid Høgdall, Nicholas J. Hawkins, Jacek Gronwald, Peter A. Fasching, Philip Crowe, Paul A. Cohen, Heather Thorne, Rebekka Wiedenhoefer, Robyn L. Ward, Paul Timpson, Katrina Tang, Soseul Sung, Deepak Subramanian, Colin J.R. Stewart, Helen Steed, Mitul Shah, Clare L. Scott, Stuart Salfinger, Matthias Ruebner, Marjorie J. Riggan, Jianyu Rao, Ganendra Raj Mohan, Carmel M. Quinn, Malcolm C. Pike, John V. Pearson, Celeste Leigh Pearce, Sang-Yoon Park, Sandra Orsulic, David Morris, Suzana Mittelstadt, Parham Minoo, Janusz Menkiszak, Simone McInerny, Constantina Mateoiu, Sakshi Mahale, Jan Lubiński, Anna Linder, Belle W.X. Lim, Winston Liauw, Na Li, Yee Leung, Jenny Lester, Angela Laslavic, Tiffany Lai, Jennifer M. Koziak, Kayla Klett, Jae-Hoon Kim, Jae-Weon Kim, Byoung-Gie Kim, Catherine J. Kennedy, Mercedes Jimenez-Linan, Anna Jakubowska, Tomasz Huzarski, Claus K. Høgdall, Anusha Hettiaratchi, Arndt Hartmann, Paul R. Harnett, Marcel Grube, Charlie Gourley, Anthony J. Gill, Blake Gilks, Zhuxuan Fu, Anna Fischer, Rhonda Farrell, Ramona Erber, Esther Elishaev, Cezary Cybulski, Joshua Cohen, Dane Cheasley, Ian Campbell, James D. Brenton, Alison H. Brand, David D.L. Bowtell, Jessica Boros, Matthias W. Beckmann, Ellen Barlow, Jennifer Alsop, Adeline Tan, Angela Chou, Ksenia Chezar, Kara L. Cushing-Haugen, Andrew Berchuck, Joellen M. Schildkraut, Holly R. Harris, Jennifer A. Doherty, Kylie-Ann Mallitt, Michael S. Anglesio, Derek S. Chiu, Chi Nam Ignatius Pang, Adelyn Bolithon, Matthew Wakefield, Kylie L. Gorringe, and Nicola S. Meagher

Abstract

Supplementary Methods

Published
2023

19. Supplementary Figures S1-S13 from Gene-Expression Profiling of Mucinous Ovarian Tumors and Comparison with Upper and Lower Gastrointestinal Tumors Identifies Markers Associated with Adverse Outcomes

Author

Susan J. Ramus, Michael L. Friedlander, Martin Köbel, Anna DeFazio, Lyndal Anderson, Paul D.P. Pharoah, Aline Talhouk, Anna H. Wu, Karin Sundfeldt, Annette Staebler, Sue K. Park, Francesmary Modugno, Gottfried E. Konecny, Stefan Kommoss, Linda E. Kelemen, Beth Y. Karlan, Paul A. James, David G. Huntsman, Estrid Høgdall, Nicholas J. Hawkins, Jacek Gronwald, Peter A. Fasching, Philip Crowe, Paul A. Cohen, Heather Thorne, Rebekka Wiedenhoefer, Robyn L. Ward, Paul Timpson, Katrina Tang, Soseul Sung, Deepak Subramanian, Colin J.R. Stewart, Helen Steed, Mitul Shah, Clare L. Scott, Stuart Salfinger, Matthias Ruebner, Marjorie J. Riggan, Jianyu Rao, Ganendra Raj Mohan, Carmel M. Quinn, Malcolm C. Pike, John V. Pearson, Celeste Leigh Pearce, Sang-Yoon Park, Sandra Orsulic, David Morris, Suzana Mittelstadt, Parham Minoo, Janusz Menkiszak, Simone McInerny, Constantina Mateoiu, Sakshi Mahale, Jan Lubiński, Anna Linder, Belle W.X. Lim, Winston Liauw, Na Li, Yee Leung, Jenny Lester, Angela Laslavic, Tiffany Lai, Jennifer M. Koziak, Kayla Klett, Jae-Hoon Kim, Jae-Weon Kim, Byoung-Gie Kim, Catherine J. Kennedy, Mercedes Jimenez-Linan, Anna Jakubowska, Tomasz Huzarski, Claus K. Høgdall, Anusha Hettiaratchi, Arndt Hartmann, Paul R. Harnett, Marcel Grube, Charlie Gourley, Anthony J. Gill, Blake Gilks, Zhuxuan Fu, Anna Fischer, Rhonda Farrell, Ramona Erber, Esther Elishaev, Cezary Cybulski, Joshua Cohen, Dane Cheasley, Ian Campbell, James D. Brenton, Alison H. Brand, David D.L. Bowtell, Jessica Boros, Matthias W. Beckmann, Ellen Barlow, Jennifer Alsop, Adeline Tan, Angela Chou, Ksenia Chezar, Kara L. Cushing-Haugen, Andrew Berchuck, Joellen M. Schildkraut, Holly R. Harris, Jennifer A. Doherty, Kylie-Ann Mallitt, Michael S. Anglesio, Derek S. Chiu, Chi Nam Ignatius Pang, Adelyn Bolithon, Matthew Wakefield, Kylie L. Gorringe, and Nicola S. Meagher

Abstract

Supplementary Figures S1-S13

Published
2023

20. Data from Gene-Expression Profiling of Mucinous Ovarian Tumors and Comparison with Upper and Lower Gastrointestinal Tumors Identifies Markers Associated with Adverse Outcomes

Author

Susan J. Ramus, Michael L. Friedlander, Martin Köbel, Anna DeFazio, Lyndal Anderson, Paul D.P. Pharoah, Aline Talhouk, Anna H. Wu, Karin Sundfeldt, Annette Staebler, Sue K. Park, Francesmary Modugno, Gottfried E. Konecny, Stefan Kommoss, Linda E. Kelemen, Beth Y. Karlan, Paul A. James, David G. Huntsman, Estrid Høgdall, Nicholas J. Hawkins, Jacek Gronwald, Peter A. Fasching, Philip Crowe, Paul A. Cohen, Heather Thorne, Rebekka Wiedenhoefer, Robyn L. Ward, Paul Timpson, Katrina Tang, Soseul Sung, Deepak Subramanian, Colin J.R. Stewart, Helen Steed, Mitul Shah, Clare L. Scott, Stuart Salfinger, Matthias Ruebner, Marjorie J. Riggan, Jianyu Rao, Ganendra Raj Mohan, Carmel M. Quinn, Malcolm C. Pike, John V. Pearson, Celeste Leigh Pearce, Sang-Yoon Park, Sandra Orsulic, David Morris, Suzana Mittelstadt, Parham Minoo, Janusz Menkiszak, Simone McInerny, Constantina Mateoiu, Sakshi Mahale, Jan Lubiński, Anna Linder, Belle W.X. Lim, Winston Liauw, Na Li, Yee Leung, Jenny Lester, Angela Laslavic, Tiffany Lai, Jennifer M. Koziak, Kayla Klett, Jae-Hoon Kim, Jae-Weon Kim, Byoung-Gie Kim, Catherine J. Kennedy, Mercedes Jimenez-Linan, Anna Jakubowska, Tomasz Huzarski, Claus K. Høgdall, Anusha Hettiaratchi, Arndt Hartmann, Paul R. Harnett, Marcel Grube, Charlie Gourley, Anthony J. Gill, Blake Gilks, Zhuxuan Fu, Anna Fischer, Rhonda Farrell, Ramona Erber, Esther Elishaev, Cezary Cybulski, Joshua Cohen, Dane Cheasley, Ian Campbell, James D. Brenton, Alison H. Brand, David D.L. Bowtell, Jessica Boros, Matthias W. Beckmann, Ellen Barlow, Jennifer Alsop, Adeline Tan, Angela Chou, Ksenia Chezar, Kara L. Cushing-Haugen, Andrew Berchuck, Joellen M. Schildkraut, Holly R. Harris, Jennifer A. Doherty, Kylie-Ann Mallitt, Michael S. Anglesio, Derek S. Chiu, Chi Nam Ignatius Pang, Adelyn Bolithon, Matthew Wakefield, Kylie L. Gorringe, and Nicola S. Meagher

Abstract

Purpose:Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features.Experimental Design:Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55).Results:Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04–7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04–1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01–1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%).Conclusions:An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies.

Published
2023

21. Supplementary Tables S1-S11 from Gene-Expression Profiling of Mucinous Ovarian Tumors and Comparison with Upper and Lower Gastrointestinal Tumors Identifies Markers Associated with Adverse Outcomes

Author

Susan J. Ramus, Michael L. Friedlander, Martin Köbel, Anna DeFazio, Lyndal Anderson, Paul D.P. Pharoah, Aline Talhouk, Anna H. Wu, Karin Sundfeldt, Annette Staebler, Sue K. Park, Francesmary Modugno, Gottfried E. Konecny, Stefan Kommoss, Linda E. Kelemen, Beth Y. Karlan, Paul A. James, David G. Huntsman, Estrid Høgdall, Nicholas J. Hawkins, Jacek Gronwald, Peter A. Fasching, Philip Crowe, Paul A. Cohen, Heather Thorne, Rebekka Wiedenhoefer, Robyn L. Ward, Paul Timpson, Katrina Tang, Soseul Sung, Deepak Subramanian, Colin J.R. Stewart, Helen Steed, Mitul Shah, Clare L. Scott, Stuart Salfinger, Matthias Ruebner, Marjorie J. Riggan, Jianyu Rao, Ganendra Raj Mohan, Carmel M. Quinn, Malcolm C. Pike, John V. Pearson, Celeste Leigh Pearce, Sang-Yoon Park, Sandra Orsulic, David Morris, Suzana Mittelstadt, Parham Minoo, Janusz Menkiszak, Simone McInerny, Constantina Mateoiu, Sakshi Mahale, Jan Lubiński, Anna Linder, Belle W.X. Lim, Winston Liauw, Na Li, Yee Leung, Jenny Lester, Angela Laslavic, Tiffany Lai, Jennifer M. Koziak, Kayla Klett, Jae-Hoon Kim, Jae-Weon Kim, Byoung-Gie Kim, Catherine J. Kennedy, Mercedes Jimenez-Linan, Anna Jakubowska, Tomasz Huzarski, Claus K. Høgdall, Anusha Hettiaratchi, Arndt Hartmann, Paul R. Harnett, Marcel Grube, Charlie Gourley, Anthony J. Gill, Blake Gilks, Zhuxuan Fu, Anna Fischer, Rhonda Farrell, Ramona Erber, Esther Elishaev, Cezary Cybulski, Joshua Cohen, Dane Cheasley, Ian Campbell, James D. Brenton, Alison H. Brand, David D.L. Bowtell, Jessica Boros, Matthias W. Beckmann, Ellen Barlow, Jennifer Alsop, Adeline Tan, Angela Chou, Ksenia Chezar, Kara L. Cushing-Haugen, Andrew Berchuck, Joellen M. Schildkraut, Holly R. Harris, Jennifer A. Doherty, Kylie-Ann Mallitt, Michael S. Anglesio, Derek S. Chiu, Chi Nam Ignatius Pang, Adelyn Bolithon, Matthew Wakefield, Kylie L. Gorringe, and Nicola S. Meagher

Abstract

Supplementary Tables S1-S11

Published
2023

22. Online-Only Tables: 1 and Online-Only Figures: 2 from Risk Assessment after Neoadjuvant Chemotherapy in Luminal Breast Cancer Using a Clinicomolecular Predictor

Author

Carsten Denkert, Ralf Kronenwett, Gunter von Minckwitz, Annette Staebler, Volkmar Müller, Silvia Darb-Esfahani, Arndt Hartmann, Jenny Furlanetto, Sherko Kümmel, Berit Maria Pfitzner, Knut Engels, Christian Schem, Frederik Marmé, Kristin Krappmann, Jens Huober, Karsten Weber, and Sibylle Loibl

Abstract

Supplementary Table 1: Multivariate analysis of the continuous mEPclin and CPS-EG scores including Ki67 status according to DFS Supplementary Figures

Published
2023

23. Data from Risk Assessment after Neoadjuvant Chemotherapy in Luminal Breast Cancer Using a Clinicomolecular Predictor

Author

Carsten Denkert, Ralf Kronenwett, Gunter von Minckwitz, Annette Staebler, Volkmar Müller, Silvia Darb-Esfahani, Arndt Hartmann, Jenny Furlanetto, Sherko Kümmel, Berit Maria Pfitzner, Knut Engels, Christian Schem, Frederik Marmé, Kristin Krappmann, Jens Huober, Karsten Weber, and Sibylle Loibl

Abstract

Purpose: This study aimed to evaluate a modified EPclin test (mEPclin), a combination of EndoPredict (EP) score, post-neoadjuvant pathologic tumor size and nodal status, for predicting the risk of distance recurrence after neoadjuvant chemotherapy (NACT) in patients with residual estrogen receptor (ER)–positive/HER2-negative breast cancer. We also compared the prognostic power of the mEPclin with that of the CPS-EG score.Experimental Design: A total of 428 formalin-fixed, paraffin-embedded tumor samples from GeparTrio and GeparQuattro studies were evaluated for mRNA expression of eight cancer-related and three reference genes. The mEPclin score was computed using a modified algorithm and predefined cut-off values were used to classify each patient at low or high risk. Primary endpoint was disease-free survival (DFS).Results: A higher continuous mEPclin score was significantly associated with increased risk of relapse [HR, 2.16; 95% confidence interval (CI), 1.86–2.51; P < 0.001] and death (HR, 2.28; 95% CI, 1.90–2.75; P < 0.001). Similarly, patients classified at high risk by dichotomous mEPclin showed significantly poorer DFS and overall survival compared with those at low risk. In contrast with CPS-EG, the mEPclin remained significantly prognostic for DFS in multivariate analysis (HR, 2.13; 95% CI, 1.73–2.63; P < 0.001). Combining CPS-EG and other clinicopathological variables with mEPclin yielded a significant improvement of the prognostic power for DFS versus without mEPclin (c-indices: 0.748 vs. 0.660; P < 0.001).Conclusions: The mEPclin score independently predicted the risk of distance recurrence and provided additional prognostic information to the CPS-EG score to assess more accurately the prognosis after NACT in the luminal non-pCR patient population. Therefore, this approach can be used to select patients for additional post-neoadjuvant therapies. Clin Cancer Res; 24(14); 3358–65. ©2018 AACR.

Published
2023

24. Supplementary Data from Endometrial Cancer Molecular Risk Stratification is Equally Prognostic for Endometrioid Ovarian Carcinoma

Author

Michael S. Anglesio, Martin Köbel, Stefan Kommoss, Tjalling Bosse, Annette Staebler, Anna V. Tinker, Naveena Singh, Jessica N. McAlpine, Ali Bashashati, Emily F. Thompson, Marco de Bruyn, Hans W. Nijman, Cornelis D. de Kroon, Ranjit Manchanda, Hans-Walter Vollert, Friedrich Kommoss, Sabine Heublein, Hans-Peter Sinn, Felix K.F. Kommoss, Philipp Harter, Andreas du Bois, Florian Heitz, Sara Brucker, Bernhard Krämer, Andreas Hartkopf, Katherine Dixon, Jana Pasternak, Lukas Feil, Samuel Leung, Janine Senz, Zhouchunyang Xia, Marcel Grube, Tayyebeh M. Nazeran, David Farnell, Rory F.L. Hammond, Daniëlla A. Scheunhage, Evan S. Cairns, Derek S. Chiu, Mary Anne Brett, Aline Talhouk, and Pauline Krämer

Abstract

Package with all supplemental figures and tables

Published
2023

25. Data from Endometrial Cancer Molecular Risk Stratification is Equally Prognostic for Endometrioid Ovarian Carcinoma

Author

Michael S. Anglesio, Martin Köbel, Stefan Kommoss, Tjalling Bosse, Annette Staebler, Anna V. Tinker, Naveena Singh, Jessica N. McAlpine, Ali Bashashati, Emily F. Thompson, Marco de Bruyn, Hans W. Nijman, Cornelis D. de Kroon, Ranjit Manchanda, Hans-Walter Vollert, Friedrich Kommoss, Sabine Heublein, Hans-Peter Sinn, Felix K.F. Kommoss, Philipp Harter, Andreas du Bois, Florian Heitz, Sara Brucker, Bernhard Krämer, Andreas Hartkopf, Katherine Dixon, Jana Pasternak, Lukas Feil, Samuel Leung, Janine Senz, Zhouchunyang Xia, Marcel Grube, Tayyebeh M. Nazeran, David Farnell, Rory F.L. Hammond, Daniëlla A. Scheunhage, Evan S. Cairns, Derek S. Chiu, Mary Anne Brett, Aline Talhouk, and Pauline Krämer

Abstract

Purpose:Endometrioid ovarian carcinoma (ENOC) is generally associated with a more favorable prognosis compared with other ovarian carcinomas. Nonetheless, current patient treatment continues to follow a “one-size-fits-all” approach. Even though tumor staging offers stratification, personalized treatments remain elusive. As ENOC shares many clinical and molecular features with its endometrial counterpart, we sought to investigate The Cancer Genome Atlas–inspired endometrial carcinoma (EC) molecular subtyping in a cohort of ENOC.Experimental Design:IHC and mutation biomarkers were used to segregate 511 ENOC tumors into four EC-inspired molecular subtypes: low-risk POLE mutant (POLEmut), moderate-risk mismatch repair deficient (MMRd), high-risk p53 abnormal (p53abn), and moderate-risk with no specific molecular profile (NSMP). Survival analysis with established clinicopathologic and subtype-specific features was performed.Results:A total of 3.5% of cases were POLEmut, 13.7% MMRd, 9.6% p53abn, and 73.2% NSMP, each showing distinct outcomes (P < 0.001) and survival similar to observations in EC. Median OS was 18.1 years in NSMP, 12.3 years in MMRd, 4.7 years in p53abn, and not reached for POLEmut cases. Subtypes were independent of stage, grade, and residual disease in multivariate analysis.Conclusions:EC-inspired molecular classification provides independent prognostic information in ENOC. Our findings support investigating molecular subtype–specific management recommendations for patients with ENOC; for example, subtypes may provide guidance when fertility-sparing treatment is desired. Similarities between ENOC and EC suggest that patients with ENOC may benefit from management strategies applied to EC and the opportunity to study those in umbrella trials.

Published
2023

27. Data from Decoding Intratumoral Heterogeneity of Breast Cancer by Multiparametric In Vivo Imaging: A Translational Study

Author

Andreas M. Schmid, Bernd J. Pichler, Robert D. Cardiff, Christian la Fougère, Konstantin Nikolaou, Sara Brucker, Alexander D. Borowsky, Gerald Reischl, Neil E. Hubbard, Olulanu H. Aina, Ursula Kohlhofer, Annette Staebler, Nina Schwenzer, Beate Wietek, Markus Hahn, Leticia Quintanilla-Martinez, Qian Chen, Johannes Schwenck, Julian Schwab, and Jennifer Schmitz

Abstract

Differential diagnosis and therapy of heterogeneous breast tumors poses a major clinical challenge. To address the need for a comprehensive, noninvasive strategy to define the molecular and functional profiles of tumors in vivo, we investigated a novel combination of metabolic PET and diffusion-weighted (DW)-MRI in the polyoma virus middle T antigen transgenic mouse model of breast cancer. The implementation of a voxelwise analysis for the clustering of intra- and intertumoral heterogeneity in this model resulted in a multiparametric profile based on [18F]Fluorodeoxyglucose ([18F]FDG)-PET and DW-MRI, which identified three distinct tumor phenotypes in vivo, including solid acinar, and solid nodular malignancies as well as cystic hyperplasia. To evaluate the feasibility of this approach for clinical use, we examined estrogen receptor-positive and progesterone receptor-positive breast tumors from five patient cases using DW-MRI and [18F]FDG-PET in a simultaneous PET/MRI system. The postsurgical in vivo PET/MRI data were correlated to whole-slide histology using the latter traditional diagnostic standard to define phenotype. By this approach, we showed how molecular, structural (microscopic, anatomic), and functional information could be simultaneously obtained noninvasively to identify precancerous and malignant subtypes within heterogeneous tumors. Combined with an automatized analysis, our results suggest that multiparametric molecular and functional imaging may be capable of providing comprehensive tumor profiling for noninvasive cancer diagnostics. Cancer Res; 76(18); 5512–22. ©2016 AACR.

Published
2023

28. Supplemental Figure Legend from Decoding Intratumoral Heterogeneity of Breast Cancer by Multiparametric In Vivo Imaging: A Translational Study

Author

Andreas M. Schmid, Bernd J. Pichler, Robert D. Cardiff, Christian la Fougère, Konstantin Nikolaou, Sara Brucker, Alexander D. Borowsky, Gerald Reischl, Neil E. Hubbard, Olulanu H. Aina, Ursula Kohlhofer, Annette Staebler, Nina Schwenzer, Beate Wietek, Markus Hahn, Leticia Quintanilla-Martinez, Qian Chen, Johannes Schwenck, Julian Schwab, and Jennifer Schmitz

Abstract

Detailed description of mean and max value analysis of ADC and [18F]FDG data of tumors of tg(PyV-mT) mice.

Published
2023

29. Data from Loss of the Ceramide Transfer Protein Augments EGF Receptor Signaling in Breast Cancer

Author

Monilola A. Olayioye, Andreas Herrmann, Thomas Korte, Simone Schmid, Stephan Duss, Jürgen Schiller, Annabell Bischoff, Tanja N. Fehm, Annette Staebler, Felix Neugart, Monika Holeiter, Nicole Weis, and Johanna Heering

Abstract

Triple-negative breast cancers (TNBC) are especially refractory to treatment due to their negative hormone receptor and ErbB2/HER2 status. Therefore, the identification of cancer-associated deregulated signaling pathways is necessary to develop improved targeted therapies. Here, we show that expression of the ceramide transfer protein CERT is reduced in TNBCs. CERT transfers ceramide from the endoplasmic reticulum to the Golgi complex for conversion into sphingomyelin (SM). We provide evidence that by regulating cellular SM levels, CERT determines the signaling output of the EGF receptor (EGFR/ErbB1), which is upregulated in approximately 70% of TNBCs. CERT downregulation in breast cancer cells enhanced ErbB1 lateral mobility, ligand-induced autophosphorylation, internalization, and chemotaxis. Together, our findings provide a link between lipid metabolism at the Golgi with signaling at the plasma membrane, thereby implicating CERT loss in the progression of TNBCs. Cancer Res; 72(11); 2855–66. ©2012 AACR.

Published
2023

30. Supplementary Figure 1 from SOX2 Expression Associates with Stem Cell State in Human Ovarian Carcinoma

Author

Claudia Lengerke, Frank Essmann, Klaus Schulze-Osthoff, Leticia Quintanilla-Martinez, Lothar Kanz, Bernd Pichler, Tanja Fehm, Falko Fend, Diethelm Wallwiener, Annette Staebler, Sven Perner, Anna Fischer, Oliver C. Rothfuss, Ursula Kohlhofer, Stefan Wiehr, Rebekka Schairer, Hui Wang, Anna Paczulla, and Petra M. Bareiss

Abstract

PDF file, 104K, SOX2 expression in primary human SOC.

Published
2023

31. Supplemental Figure I from Decoding Intratumoral Heterogeneity of Breast Cancer by Multiparametric In Vivo Imaging: A Translational Study

Author

Andreas M. Schmid, Bernd J. Pichler, Robert D. Cardiff, Christian la Fougère, Konstantin Nikolaou, Sara Brucker, Alexander D. Borowsky, Gerald Reischl, Neil E. Hubbard, Olulanu H. Aina, Ursula Kohlhofer, Annette Staebler, Nina Schwenzer, Beate Wietek, Markus Hahn, Leticia Quintanilla-Martinez, Qian Chen, Johannes Schwenck, Julian Schwab, and Jennifer Schmitz

Abstract

Mean (blue) and maximal (red) ADC and [18F]FDG uptake values of the same representative 8 tumors: VOIs were drawn on the basis of the T2-weighted TSE MRI data, and transferred to the appropriate PET and ADC data. The mean and max values were determined. The comparison between mean or maximal values between the tumors revealed different trends.

Published
2023

32. Supplementary Methods from SOX2 Expression Associates with Stem Cell State in Human Ovarian Carcinoma

Author

Claudia Lengerke, Frank Essmann, Klaus Schulze-Osthoff, Leticia Quintanilla-Martinez, Lothar Kanz, Bernd Pichler, Tanja Fehm, Falko Fend, Diethelm Wallwiener, Annette Staebler, Sven Perner, Anna Fischer, Oliver C. Rothfuss, Ursula Kohlhofer, Stefan Wiehr, Rebekka Schairer, Hui Wang, Anna Paczulla, and Petra M. Bareiss

Abstract

PDF file, 99K, Includes additional information regarding Primer Sequences used for Real Time PCR analysis, Tissue Microarray Analysis, Lentiviral transduction, and PET/MRI analysis.

Published
2023

33. Supplementary Figure 3 from SOX2 Expression Associates with Stem Cell State in Human Ovarian Carcinoma

Author

Claudia Lengerke, Frank Essmann, Klaus Schulze-Osthoff, Leticia Quintanilla-Martinez, Lothar Kanz, Bernd Pichler, Tanja Fehm, Falko Fend, Diethelm Wallwiener, Annette Staebler, Sven Perner, Anna Fischer, Oliver C. Rothfuss, Ursula Kohlhofer, Stefan Wiehr, Rebekka Schairer, Hui Wang, Anna Paczulla, and Petra M. Bareiss

Abstract

PDF file, 58K, Analysis of primary SOC cells transduced with SOX2-overexpressing and control lentiviruses.

Published
2023

34. Supplementary Figure 4 from Loss of the Ceramide Transfer Protein Augments EGF Receptor Signaling in Breast Cancer

Author

Monilola A. Olayioye, Andreas Herrmann, Thomas Korte, Simone Schmid, Stephan Duss, Jürgen Schiller, Annabell Bischoff, Tanja N. Fehm, Annette Staebler, Felix Neugart, Monika Holeiter, Nicole Weis, and Johanna Heering

Abstract

PDF file - 81K, Downregulation of SM synthases recapitulates the effects of CERT depletion on EGF-induced Akt activation and cell migration

Published
2023

35. Supplemental Tables from Decoding Intratumoral Heterogeneity of Breast Cancer by Multiparametric In Vivo Imaging: A Translational Study

Author

Andreas M. Schmid, Bernd J. Pichler, Robert D. Cardiff, Christian la Fougère, Konstantin Nikolaou, Sara Brucker, Alexander D. Borowsky, Gerald Reischl, Neil E. Hubbard, Olulanu H. Aina, Ursula Kohlhofer, Annette Staebler, Nina Schwenzer, Beate Wietek, Markus Hahn, Leticia Quintanilla-Martinez, Qian Chen, Johannes Schwenck, Julian Schwab, and Jennifer Schmitz

Abstract

Supplemental Table I is a list of abbreviations, Supplemental Table II contains the classification parameters for the different phenotypes in the mouse model and Supplemental Table III contains a summary of clinical data correlating image-derived and histology-derived tumor volumes.

Published
2023

36. Supplementary Figure 3 from Loss of the Ceramide Transfer Protein Augments EGF Receptor Signaling in Breast Cancer

Author

Monilola A. Olayioye, Andreas Herrmann, Thomas Korte, Simone Schmid, Stephan Duss, Jürgen Schiller, Annabell Bischoff, Tanja N. Fehm, Annette Staebler, Felix Neugart, Monika Holeiter, Nicole Weis, and Johanna Heering

Abstract

PDF file - 155K, A second CERT-specific siRNA confirms the impact on EGF-induced Akt activation, cell migration and focal adhesion clustering

Published
2023

38. Supplementary Figure 2 from SOX2 Expression Associates with Stem Cell State in Human Ovarian Carcinoma

Author

Claudia Lengerke, Frank Essmann, Klaus Schulze-Osthoff, Leticia Quintanilla-Martinez, Lothar Kanz, Bernd Pichler, Tanja Fehm, Falko Fend, Diethelm Wallwiener, Annette Staebler, Sven Perner, Anna Fischer, Oliver C. Rothfuss, Ursula Kohlhofer, Stefan Wiehr, Rebekka Schairer, Hui Wang, Anna Paczulla, and Petra M. Bareiss

Abstract

PDF file, 127K, Treatment of OVCAR-3 cells with an alternative SOX2 shRNA construct.

Published
2023

39. Supplementary Figure 5 from SOX2 Expression Associates with Stem Cell State in Human Ovarian Carcinoma

Author

Claudia Lengerke, Frank Essmann, Klaus Schulze-Osthoff, Leticia Quintanilla-Martinez, Lothar Kanz, Bernd Pichler, Tanja Fehm, Falko Fend, Diethelm Wallwiener, Annette Staebler, Sven Perner, Anna Fischer, Oliver C. Rothfuss, Ursula Kohlhofer, Stefan Wiehr, Rebekka Schairer, Hui Wang, Anna Paczulla, and Petra M. Bareiss

Abstract

PDF file, 1265K, Histological and immunohistochemical analysis of explanted tumors generated from 50.000 SOX2-overexpressing and control Caov-3 cells, respectively.

Published
2023

42. Supplementary Figure 6 from SOX2 Expression Associates with Stem Cell State in Human Ovarian Carcinoma

Author

Claudia Lengerke, Frank Essmann, Klaus Schulze-Osthoff, Leticia Quintanilla-Martinez, Lothar Kanz, Bernd Pichler, Tanja Fehm, Falko Fend, Diethelm Wallwiener, Annette Staebler, Sven Perner, Anna Fischer, Oliver C. Rothfuss, Ursula Kohlhofer, Stefan Wiehr, Rebekka Schairer, Hui Wang, Anna Paczulla, and Petra M. Bareiss

Abstract

PDF file, 112K, Apoptotic effects of staurosporine (STS) and TRAIL treatment in SOX2-modified and control Caov-3 and OVCAR-3 cells.

Published
2023

43. Supplementary Figure 4 from SOX2 Expression Associates with Stem Cell State in Human Ovarian Carcinoma

Author

Claudia Lengerke, Frank Essmann, Klaus Schulze-Osthoff, Leticia Quintanilla-Martinez, Lothar Kanz, Bernd Pichler, Tanja Fehm, Falko Fend, Diethelm Wallwiener, Annette Staebler, Sven Perner, Anna Fischer, Oliver C. Rothfuss, Ursula Kohlhofer, Stefan Wiehr, Rebekka Schairer, Hui Wang, Anna Paczulla, and Petra M. Bareiss

Abstract

PDF file, 1094K, Characterization of OVCAR-3 cells transduced with the SOX2 enhancer reporter construct.

Published
2023

45. Supplemental Material from Decoding Intratumoral Heterogeneity of Breast Cancer by Multiparametric In Vivo Imaging: A Translational Study

Author

Andreas M. Schmid, Bernd J. Pichler, Robert D. Cardiff, Christian la Fougère, Konstantin Nikolaou, Sara Brucker, Alexander D. Borowsky, Gerald Reischl, Neil E. Hubbard, Olulanu H. Aina, Ursula Kohlhofer, Annette Staebler, Nina Schwenzer, Beate Wietek, Markus Hahn, Leticia Quintanilla-Martinez, Qian Chen, Johannes Schwenck, Julian Schwab, and Jennifer Schmitz

Abstract

More detailed description of ex-vivo procedures of mouse tumor samples

Published
2023

48. A bead-based western for high-throughput cellular signal transduction analyses

Author

Fridolin Treindl, Benjamin Ruprecht, Yvonne Beiter, Silke Schultz, Anette Döttinger, Annette Staebler, Thomas O. Joos, Simon Kling, Oliver Poetz, Tanja Fehm, Hans Neubauer, Bernhard Kuster, and Markus F. Templin

Subjects
Science
Abstract

Dissecting cellular signalling requires the analysis of large numbers of proteins. Here the authors describe DigiWest, a high-throughput protein detection method that combines the concept of western and widely-used bead array systems that allows rapid quantification of hundreds of specific proteins.

Published
2016
Full Text
View/download PDF

49. Validated biomarker assays confirm that <scp>ARID1A</scp> loss is confounded with <scp>MMR</scp> deficiency, <scp> CD8 + TIL </scp> infiltration, and provides no independent prognostic value in endometriosis‐associated ovarian carcinomas

Author

Karolin Heinze, Tayyebeh M Nazeran, Sandra Lee, Pauline Krämer, Evan S Cairns, Derek S Chiu, Samuel CY Leung, Eun Young Kang, Nicola S Meagher, Catherine J Kennedy, Jessica Boros, Friedrich Kommoss, Hans‐Walter Vollert, Florian Heitz, Andreas Bois, Philipp Harter, Marcel Grube, Bernhard Kraemer, Annette Staebler, Felix KF Kommoss, Sabine Heublein, Hans‐Peter Sinn, Naveena Singh, Angela Laslavic, Esther Elishaev, Alex Olawaiye, Kirsten Moysich, Francesmary Modugno, Raghwa Sharma, Alison H Brand, Paul R Harnett, Anna DeFazio, Renée T Fortner, Jan Lubinski, Marcin Lener, Aleksandra Tołoczko‐Grabarek, Cezary Cybulski, Helena Gronwald, Jacek Gronwald, Penny Coulson, Mona A El‐Bahrawy, Michael E Jones, Minouk J Schoemaker, Anthony J Swerdlow, Kylie L Gorringe, Ian Campbell, Linda Cook, Simon A Gayther, Michael E Carney, Yurii B Shvetsov, Brenda Y Hernandez, Lynne R Wilkens, Marc T Goodman, Constantina Mateoiu, Anna Linder, Karin Sundfeldt, Linda E Kelemen, Aleksandra Gentry‐Maharaj, Martin Widschwendter, Usha Menon, Kelly L Bolton, Jennifer Alsop, Mitul Shah, Mercedes Jimenez‐Linan, Paul DP Pharoah, James D Brenton, Kara L Cushing‐Haugen, Holly R Harris, Jennifer A Doherty, Blake Gilks, Prafull Ghatage, David G Huntsman, Gregg S Nelson, Anna V Tinker, Cheng‐Han Lee, Ellen L Goode, Brad H Nelson, Susan J Ramus, Stefan Kommoss, Aline Talhouk, Martin Köbel, and Michael S Anglesio

Subjects
Ovarian Neoplasms, Canada, Brain Neoplasms, Carcinoma, Endometriosis, Nuclear Proteins, CD8-Positive T-Lymphocytes, Prognosis, Article, Pathology and Forensic Medicine, DNA-Binding Proteins, Neoplastic Syndromes, Hereditary, Mutation, Biomarkers, Tumor, Humans, Female, Colorectal Neoplasms, Carcinoma, Endometrioid, Transcription Factors
Abstract

ARID1A (BAF250a) is a component of the SWI/SNF chromatin modifying complex, plays an important tumour suppressor role, and is considered prognostic in several malignancies. However, in ovarian carcinomas there are contradictory reports on its relationship to outcome, immune response, and correlation with clinicopathological features. We assembled a series of 1,623 endometriosis-associated ovarian carcinomas, including 1,078 endometrioid (ENOC) and 545 clear cell (CCOC) ovarian carcinomas through combining resources of the Ovarian Tumor Tissue Analysis (OTTA) Consortium, the Canadian Ovarian Unified Experimental Resource (COEUR), local, and collaborative networks. Validated immunohistochemical surrogate assays for ARID1A mutations were applied to all samples. We investigated associations between ARID1A loss/mutation, clinical features, outcome, CD8+ tumour-infiltrating lymphocytes (CD8+ TIL), and DNA mismatch repair deficiency (MMRd). ARID1A loss was observed in 42% of CCOC and 25% of ENOC. We found no associations between ARID1A loss and outcomes, stage, age, or CD8+ TIL status in CCOC. Similarly, we found no association with outcome or stage in endometrioid cases. In ENOC, ARID1A loss was more prevalent in younger patients (p=0.012), and associated with MMRd (p

Published
2022

50. Treatment and survival of patients with malignant ovarian sex cord-stromal cell tumours : An analysis of the Arbeitsgemeinschaft für Gynäkologische Onkologie (AGO) study group CORSETT database

Author

Maximilian Klar, Helmut Plett, Philipp Harter, Florian Heitz, Stefan Kommoss, Andreas Daniel Hartkopf, Marcel Grube, Eva Roser, Jalid Sehouli, Iona Braicu, Bastian Czogalla, Alexander Burges, Michaela Bossart, Mir Fuad Hasanov, Teresa Link, Annette Staebler, Doris Mayr, Paul Buderath, and Annette Hasenburg

Subjects
Oncology, Medizin, Surgery, General Medicine
Abstract

Background: Malignant sex cord-stromal cell tumours (SCST) account for only 7% of ovarian malignancies. The Arbeitsgemeinschaft fuer Gynaekologische Onkologie (AGO) study group has established a clinicopathological database to provide an overview of the current treatment strategies and survival of SCST patients and to identify research needs. Methods: Twenty centres provided mixed retro- and prospective data of patients with tumour specimens and second-opinion pathology review treated between 2000 and 2014. Descriptive analyses of treatment strategies, Kaplan–Meier curves and cox regression analyses were conducted. Results: Two hundred and sixty-two SCST patients were included. One hundred and ninety-one Granulosa-cell tumour (GCT) and 17 Sertoli-Leydig cell tumour (SLCT) patients were stage I disease (>80%). Forty four GCT (18.7%) and two (8.3%) SLCT patients received adjuvant systemic treatment. After a median observation time of 78.2 months, 46% of all SCST patients experienced disease recurrence, treated predominantly with secondary debulking surgery (> 90%). Advanced FIGO stage, lymph node involvement and intra-operative capsule rupture were associated with disease recurrence on univariate analysis (all p < 0.05). Median OS time was not reached. Discussion: In this analysis of SCST patients, adjuvant chemotherapy was unable to prevent disease recurrence. Despite high recurrence rates, overall survival rates were excellent. in press

Published
2023

Catalog

Books, media, physical & digital resources
See catalog results