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1. An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer

Author

Lindskrog, Sia Viborg, Prip, Frederik, Lamy, Philippe, Taber, Ann, Groeneveld, Clarice S., Birkenkamp-Demtröder, Karin, Jensen, Jørgen Bjerggaard, Strandgaard, Trine, Nordentoft, Iver, Christensen, Emil, Sokac, Mateo, Birkbak, Nicolai J., Maretty, Lasse, Hermann, Gregers G., Petersen, Astrid C., Weyerer, Veronika, Grimm, Marc-Oliver, Horstmann, Marcus, Sjödahl, Gottfrid, Höglund, Mattias, Steiniche, Torben, Mogensen, Karin, de Reyniès, Aurélien, Nawroth, Roman, Jordan, Brian, Lin, Xiaoqi, Dragicevic, Dejan, Ward, Douglas G., Goel, Anshita, Hurst, Carolyn D., Raman, Jay D., Warrick, Joshua I., Segersten, Ulrika, Sikic, Danijel, van Kessel, Kim E. M., Maurer, Tobias, Meeks, Joshua J., DeGraff, David J., Bryan, Richard T., Knowles, Margaret A., Simic, Tatjana, Hartmann, Arndt, Zwarthoff, Ellen C., Malmström, Per-Uno, Malats, Núria, Real, Francisco X., and Dyrskjøt, Lars

Published
2021
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2. Abstract 6075: Comprehensive genomic characterization of early-stage bladder cancer from 438 patients by whole genome- and exome sequencing

Author

Prip, Frederik, primary, Lamy, Philippe, additional, Nordentoft, Iver, additional, Lindskrog, Sia Viborg, additional, Strandgaard, Trine, additional, Birkenkamp-Demtröder, Karin, additional, Hermann, Gregers G., additional, Petersen, Astrid C., additional, Bahlinger, Veronika, additional, Grimm, Marc-Oliver, additional, Horstmann, Marcus, additional, Mogensen, Karin, additional, Nawroth, Roman, additional, Segersten, Ulrika, additional, Sikic, Danijel, additional, van Kessel, Kim E. M, additional, Maurer, Tobias, additional, Simic, Tatjana, additional, Hartmann, Arndt, additional, Zwarthoff, Ellen C. C., additional, Malmström, Per-Uno, additional, Steiniche, Torben, additional, Jensen, Jørgen Bjerggaard, additional, Malats, Núria, additional, Real, Francisco X., additional, and Dyrskjøt, Lars, additional

Published
2023
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3. Supplementary table S2 from Molecular Markers Increase Precision of the European Association of Urology Non–Muscle-Invasive Bladder Cancer Progression Risk Groups

Author

van Kessel, Kim E.M., primary, van der Keur, Kirstin A., primary, Dyrskjøt, Lars, primary, Algaba, Ferran, primary, Welvaart, Naeromy Y.C., primary, Beukers, Willemien, primary, Segersten, Ulrika, primary, Keck, Bastian, primary, Maurer, Tobias, primary, Simic, Tatjana, primary, Horstmann, Marcus, primary, Grimm, Marc-Oliver, primary, Hermann, Gregers G., primary, Mogensen, Karin, primary, Hartmann, Arndt, primary, Harving, Niels, primary, Petersen, Astrid C., primary, Jensen, Jørgen B., primary, Junker, Kerstin, primary, Boormans, Joost L., primary, Real, Francisco X., primary, Malats, Núria, primary, Malmström, Per-Uno, primary, Ørntoft, Torben F., primary, and Zwarthoff, Ellen C., primary

Published
2023
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4. Supplementary figure S7 from Molecular Markers Increase Precision of the European Association of Urology Non–Muscle-Invasive Bladder Cancer Progression Risk Groups

Author

van Kessel, Kim E.M., primary, van der Keur, Kirstin A., primary, Dyrskjøt, Lars, primary, Algaba, Ferran, primary, Welvaart, Naeromy Y.C., primary, Beukers, Willemien, primary, Segersten, Ulrika, primary, Keck, Bastian, primary, Maurer, Tobias, primary, Simic, Tatjana, primary, Horstmann, Marcus, primary, Grimm, Marc-Oliver, primary, Hermann, Gregers G., primary, Mogensen, Karin, primary, Hartmann, Arndt, primary, Harving, Niels, primary, Petersen, Astrid C., primary, Jensen, Jørgen B., primary, Junker, Kerstin, primary, Boormans, Joost L., primary, Real, Francisco X., primary, Malats, Núria, primary, Malmström, Per-Uno, primary, Ørntoft, Torben F., primary, and Zwarthoff, Ellen C., primary

Published
2023
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5. Placental Tissue Destruction and Insufficiency From COVID-19 Causes Stillbirth and Neonatal Death From Hypoxic-Ischemic Injury : A Study of 68 Cases With SARS-CoV-2 Placentitis From 12 Countries

Author

Schwartz, David A., Avvad-Portari, Elyzabeth, Babal, Pavel, Baldewijns, Marcella, Blomberg, Marie, Bouachba, Amine, Camacho, Jessica, Collardeau-Frachon, Sophie, Colson, Arthur, Dehaene, Isabelle, Carles Ferreres, Joan, Fitzgerald, Brendan, Garrido-Pontnou, Marta, Gergis, Hazem, Hargitai, Beata, Cecilia Helguera-Repetto, A., Holmström, Sandra, Liliane Irles, Claudine, Leijonhfvud, Åsa, Libbrecht, Sasha, Marton, Tamas, McEntagart, Noel, Molina, James T., Morotti, Raffaella, Nadal, Alfons, Navarro, Alexandra, Nelander, Maria, Oviedo, Angelica, Oyamada Otani, Andre Ricardo, Papadogiannakis, Nikos, Petersen, Astrid C., Roberts, Drucilla J., Saad, Ali G., Sand, Anna, Schoenmakers, Sam, Sehn, Jennifer K., Simpson, Preston R., Thomas, Kristen, Yolotzin Valdespino-Vazquez, M., van der Meeren, Lotte E., Van Dorpe, Jo, Verdijk, Robert M., Watkins, Jaclyn C., Zaigham, Mehreen, Schwartz, David A., Avvad-Portari, Elyzabeth, Babal, Pavel, Baldewijns, Marcella, Blomberg, Marie, Bouachba, Amine, Camacho, Jessica, Collardeau-Frachon, Sophie, Colson, Arthur, Dehaene, Isabelle, Carles Ferreres, Joan, Fitzgerald, Brendan, Garrido-Pontnou, Marta, Gergis, Hazem, Hargitai, Beata, Cecilia Helguera-Repetto, A., Holmström, Sandra, Liliane Irles, Claudine, Leijonhfvud, Åsa, Libbrecht, Sasha, Marton, Tamas, McEntagart, Noel, Molina, James T., Morotti, Raffaella, Nadal, Alfons, Navarro, Alexandra, Nelander, Maria, Oviedo, Angelica, Oyamada Otani, Andre Ricardo, Papadogiannakis, Nikos, Petersen, Astrid C., Roberts, Drucilla J., Saad, Ali G., Sand, Anna, Schoenmakers, Sam, Sehn, Jennifer K., Simpson, Preston R., Thomas, Kristen, Yolotzin Valdespino-Vazquez, M., van der Meeren, Lotte E., Van Dorpe, Jo, Verdijk, Robert M., Watkins, Jaclyn C., and Zaigham, Mehreen

Abstract

Context: Perinatal death is an increasingly important problem as the coronavirus disease 2019 (COVID-19) pandemic continues, but the mechanism of death has been unclear. Objective: To evaluate the role of the placenta in causing stillbirth and neonatal death following maternal infection with COVID-19 and confirmed placental positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Design: Case-based retrospective clinicopathologic analysis by a multinational group of 44 perinatal specialists from 12 countries of placental and autopsy pathology findings from 64 stillborns and 4 neonatal deaths having placentas testing positive for SARS-CoV-2 following delivery to mothers with COVID-19. Results: Of the 3 findings constituting SARS-CoV-2 placentitis, all 68 placentas had increased fibrin deposition and villous trophoblast necrosis and 66 had chronic histiocytic intervillositis. Sixty-three placentas had massive perivillous fibrin deposition. Severe destructive placental disease from SARS-CoV-2 placentitis averaged 77.7% tissue involvement. Other findings included multiple intervillous thrombi (37%; 25 of 68) and chronic villitis (32%; 22 of 68). The majority (19; 63%) of the 30 autopsies revealed no significant fetal abnormalities except for intrauterine hypoxia and asphyxia. Among all 68 cases, SARS-CoV-2 was detected from a body specimen in 16 of 28 cases tested, most frequently from nasopharyngeal swabs. Four autopsied stillborns had SARS-CoV-2 identified in internal organs. Conclusions: The pathology abnormalities composing SARS-CoV-2 placentitis cause widespread and severe placental destruction resulting in placental malperfusion and insufficiency. In these cases, intrauterine and perinatal death likely results directly from placental insufficiency and fetal hypoxic-ischemic injury. There was no evidence that SARS-CoV-2 involvement of the fetus had a role in causing these deaths.

Published
2022
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6. Placental Tissue Destruction and Insufficiency From COVID-19 Causes Stillbirth and Neonatal Death From Hypoxic-Ischemic Injury:A Study of 68 Cases With SARS-CoV-2 Placentitis From 12 Countries

Author

Schwartz, David A., Avvad-Portari, Elyzabeth, Babal, Pavel, Baldewijns, Marcella, Blomberg, Marie, Bouachba, Amine, Camacho, Jessica, Collardeau-Frachon, Sophie, Colson, Arthur, Dehaene, Isabelle, Ferreres, Joan Carles, Fitzgerald, Brendan, Garrido-Pontnou, Marta, Gergis, Hazem, Hargitai, Beata, Cecilia Helguera-Repetto, A., Holmstrom, Sandra, Irles, Claudine Liliane, Leijonhfvud, Asa, Libbrecht, Sasha, Marton, Tamas, McEntagart, Noel, Molina, James T., Morotti, Raffaella, Nadal, Alfons, Navarro, Alexandra, Nelander, Maria, Oviedo, Angelica, Otani, Andre Ricardo Oyamada, Papadogiannakis, Nikos, Petersen, Astrid C., Roberts, Drucilla J., Saad, Ali G., Sand, Anna, Schoenmakers, Sam, Sehn, Jennifer K., Simpson, Preston R., Thomas, Kristen, Yolotzin Valdespino-Vazquez, M., Van der Meeren, Lotte E., Van Dorpe, Jo, Verdijk, Robert M., Watkins, Jaclyn C., Zaigham, Mehreen, Schwartz, David A., Avvad-Portari, Elyzabeth, Babal, Pavel, Baldewijns, Marcella, Blomberg, Marie, Bouachba, Amine, Camacho, Jessica, Collardeau-Frachon, Sophie, Colson, Arthur, Dehaene, Isabelle, Ferreres, Joan Carles, Fitzgerald, Brendan, Garrido-Pontnou, Marta, Gergis, Hazem, Hargitai, Beata, Cecilia Helguera-Repetto, A., Holmstrom, Sandra, Irles, Claudine Liliane, Leijonhfvud, Asa, Libbrecht, Sasha, Marton, Tamas, McEntagart, Noel, Molina, James T., Morotti, Raffaella, Nadal, Alfons, Navarro, Alexandra, Nelander, Maria, Oviedo, Angelica, Otani, Andre Ricardo Oyamada, Papadogiannakis, Nikos, Petersen, Astrid C., Roberts, Drucilla J., Saad, Ali G., Sand, Anna, Schoenmakers, Sam, Sehn, Jennifer K., Simpson, Preston R., Thomas, Kristen, Yolotzin Valdespino-Vazquez, M., Van der Meeren, Lotte E., Van Dorpe, Jo, Verdijk, Robert M., Watkins, Jaclyn C., and Zaigham, Mehreen

Abstract

Context.-Perinatal death is an increasingly important problem as the coronavirus disease 2019 (COVID-19) pandemic continues, but the mechanism of death has been unclear. Objective.-To evaluate the role of the placenta in causing stillbirth and neonatal death following maternal infection with COVID-19 and confirmed placental positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Design.-Case-based retrospective clinicopathologic analysis by a multinational group of 44 perinatal specialists from 12 countries of placental and autopsy pathology findings from 64 stillborns and 4 neonatal deaths having placentas testing positive for SARS-CoV-2 following delivery to mothers with COVID-19. Results.-Of the 3 findings constituting SARS-CoV-2 placentitis, all 68 placentas had increased fibrin deposition and villous trophoblast necrosis and 66 had chronic histiocytic intervillositis. Sixty-three placentas had massive perivillous fibrin deposition. Severe destructive placental disease from SARS-CoV-2 placentitis averaged 77.7% tissue involvement. Other findings included multiple intervillous thrombi (37%; 25 of 68) and chronic villitis (32%; 22 of 68). The majority (19; 63%) of the 30 autopsies revealed no significant fetal abnormalities except for intrauterine hypoxia and asphyxia. Among all 68 cases, SARS-CoV-2 was detected from a body specimen in 16 of 28 cases tested, most frequently from nasopharyngeal swabs. Four autopsied stillborns had SARS-CoV-2 identified in internal organs. Conclusions.-The pathology abnormalities composing SARS-CoV-2 placentitis cause widespread and severe placental destruction resulting in placental malperfusion and insufficiency. In these cases, intrauterine and perinatal death likely results directly from placental insufficiency and fetal hypoxic-ischemic injury. There was no evidence that SARS-CoV-2 involvement of the fetus had a role in causing these deaths.

Published
2022

7. Placental Tissue Destruction and Insufficiency from COVID-19 Causes Stillbirth and Neonatal Death from Hypoxic-Ischemic Injury: A Study of 68 Cases with SARS-CoV-2 Placentitis from 12 Countries

Author

Pathologie Pathologen staf, Schwartz, David A, Avvad-Portari, Elyzabeth, Babál, Pavel, Baldewijns, Marcella, Blomberg, Marie, Bouachba, Amine, Camacho, Jessica, Collardeau-Frachon, Sophie, Colson, Arthur, Dehaene, Isabelle, Ferreres, Joan Carles, Fitzgerald, Brendan, Garrido-Pontnou, Marta, Gerges, Hazem, Hargitai, Beata, Helguera-Repetto, A Cecilia, Holmström, Sandra, Irles, Claudine Liliane, Leijonhfvud, Åsa, Libbrecht, Sasha, Marton, Tamás, McEntagart, Noel, Molina, James T, Morotti, Raffaella, Nadal, Alfons, Navarro, Alexandra, Nelander, Maria, Oviedo, Angelica, Oyamada Otani, Andre Ricardo, Papadogiannakis, Nikos, Petersen, Astrid C, Roberts, Drucilla J, Saad, Ali G, Sand, Anna, Schoenmakers, Sam, Sehn, Jennifer K, Simpson, Preston R, Thomas, Kristen, Valdespino-Vázquez, M Yolotzin, van der Meeren, Lotte E, Van Dorpe, Jo, Verdijk, Robert M, Watkins, Jaclyn C, Zaigham, Mehreen, Pathologie Pathologen staf, Schwartz, David A, Avvad-Portari, Elyzabeth, Babál, Pavel, Baldewijns, Marcella, Blomberg, Marie, Bouachba, Amine, Camacho, Jessica, Collardeau-Frachon, Sophie, Colson, Arthur, Dehaene, Isabelle, Ferreres, Joan Carles, Fitzgerald, Brendan, Garrido-Pontnou, Marta, Gerges, Hazem, Hargitai, Beata, Helguera-Repetto, A Cecilia, Holmström, Sandra, Irles, Claudine Liliane, Leijonhfvud, Åsa, Libbrecht, Sasha, Marton, Tamás, McEntagart, Noel, Molina, James T, Morotti, Raffaella, Nadal, Alfons, Navarro, Alexandra, Nelander, Maria, Oviedo, Angelica, Oyamada Otani, Andre Ricardo, Papadogiannakis, Nikos, Petersen, Astrid C, Roberts, Drucilla J, Saad, Ali G, Sand, Anna, Schoenmakers, Sam, Sehn, Jennifer K, Simpson, Preston R, Thomas, Kristen, Valdespino-Vázquez, M Yolotzin, van der Meeren, Lotte E, Van Dorpe, Jo, Verdijk, Robert M, Watkins, Jaclyn C, and Zaigham, Mehreen

Published
2022

9. Placental Tissue Destruction and Insufficiency From COVID-19 Causes Stillbirth and Neonatal Death From Hypoxic-Ischemic Injury

Author

Schwartz, David A., primary, Avvad-Portari, Elyzabeth, additional, Babál, Pavel, additional, Baldewijns, Marcella, additional, Blomberg, Marie, additional, Bouachba, Amine, additional, Camacho, Jessica, additional, Collardeau-Frachon, Sophie, additional, Colson, Arthur, additional, Dehaene, Isabelle, additional, Ferreres, Joan Carles, additional, Fitzgerald, Brendan, additional, Garrido-Pontnou, Marta, additional, Gergis, Hazem, additional, Hargitai, Beata, additional, Helguera-Repetto, A. Cecilia, additional, Holmström, Sandra, additional, Irles, Claudine Liliane, additional, Leijonhfvud, Åsa, additional, Libbrecht, Sasha, additional, Marton, Tamás, additional, McEntagart, Noel, additional, Molina, James T., additional, Morotti, Raffaella, additional, Nadal, Alfons, additional, Navarro, Alexandra, additional, Nelander, Maria, additional, Oviedo, Angelica, additional, Otani, Andre Ricardo Oyamada, additional, Papadogiannakis, Nikos, additional, Petersen, Astrid C., additional, Roberts, Drucilla J., additional, Saad, Ali G., additional, Sand, Anna, additional, Schoenmakers, Sam, additional, Sehn, Jennifer K., additional, Simpson, Preston R., additional, Thomas, Kristen, additional, Valdespino-Vázquez, M. Yolotzin, additional, van der Meeren, Lotte E., additional, Van Dorpe, Jo, additional, Verdijk, Robert M., additional, Watkins, Jaclyn C., additional, and Zaigham, Mehreen, additional

Published
2022
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12. An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer

Author

Viborg Lindskrog, Sia, Prip, Frederik, Lamy, Philippe, Taber, Ann, Groeneveld, Clarice S., Birkenkamp-Demtröder, Karin, Bjerggaard Jensen, Jørgen, Strandgaard, Trine, Nordentoft, Iver, Christensen, Emil, Sokac, Mateo, Birkbak, Nicolai J., Maretty, Lasse, Hermann, Gregers G., Petersen, Astrid C., Weyerer, Veronika, Grimm, Marc-Oliver, Horstmann, Marcus, Sjödahl, Gottfrid, Höglund, Mattias, Steiniche, Torben, Mogensen, Karin, de Reyniès, Aurélien, Nawroth, Roman, Jordan, Brian, Lin, Xiaoqi, Dragicevic, Dejan, Ward, Douglas G., Goel, Anshita, Hurst, Carolyn D., Raman, Jay D., Warrick, Joshua I., Segersten, Ulrika, Sikic, Danijel, van Kessel, Kim E. M., Maurer, Tobias, Meeks, Joshua J., DeGraff, David J., Bryan, Richard T., Knowles, Margaret A., Simic, Tatjana, Hartmann, Arndt, Zwarthoff, Ellen C., Malmström, Per-Uno, Malats, Núria, Real, Francisco X., Dyrskjøt, Lars, Viborg Lindskrog, Sia, Prip, Frederik, Lamy, Philippe, Taber, Ann, Groeneveld, Clarice S., Birkenkamp-Demtröder, Karin, Bjerggaard Jensen, Jørgen, Strandgaard, Trine, Nordentoft, Iver, Christensen, Emil, Sokac, Mateo, Birkbak, Nicolai J., Maretty, Lasse, Hermann, Gregers G., Petersen, Astrid C., Weyerer, Veronika, Grimm, Marc-Oliver, Horstmann, Marcus, Sjödahl, Gottfrid, Höglund, Mattias, Steiniche, Torben, Mogensen, Karin, de Reyniès, Aurélien, Nawroth, Roman, Jordan, Brian, Lin, Xiaoqi, Dragicevic, Dejan, Ward, Douglas G., Goel, Anshita, Hurst, Carolyn D., Raman, Jay D., Warrick, Joshua I., Segersten, Ulrika, Sikic, Danijel, van Kessel, Kim E. M., Maurer, Tobias, Meeks, Joshua J., DeGraff, David J., Bryan, Richard T., Knowles, Margaret A., Simic, Tatjana, Hartmann, Arndt, Zwarthoff, Ellen C., Malmström, Per-Uno, Malats, Núria, Real, Francisco X., and Dyrskjøt, Lars

Abstract

The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we perform an integrative multi-omics analysis of patients diagnosed with NMIBC (n=834). Transcriptomic analysis identifies four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provide independent prognostic value beyond established prognostic clinicopathological parameters. High chromosomal instability, p53-pathway disruption and APOBEC-related mutations are significantly associated with transcriptomic class 2a and poor outcome. RNA-derived immune cell infiltration is associated with chromosomally unstable tumors and enriched in class 2b. Spatial proteomics analysis confirms the higher infiltration of class 2b tumors and demonstrates an association between higher immune cell infiltration and lower recurrence rates. Finally, the independent prognostic value of the transcriptomic classes is documented in 1228 validation samples using a single sample classification tool. The classifier provides a framework for biomarker discovery and for optimizing treatment and surveillance in next-generation clinical trials.

Published
2021
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14. An integrated multi-omics analysis identifies clinically relevant molecular subtypes of non-muscle-invasive bladder cancer

Author

Lindskrog, Sia Viborg, primary, Prip, Frederik F., additional, Lamy, Philippe, additional, Taber, Ann, additional, Groeneveld, Clarice S., additional, Birkenkamp-Demtröder, Karin, additional, Jensen, Jørgen Bjerggaard, additional, Strandgaard, Trine, additional, Nordentoft, Iver, additional, Christensen, Emil, additional, Sokac, Mateo, additional, Birkbak, Nicolai J., additional, Maretty, Lasse, additional, Hermann, Gregers G., additional, Petersen, Astrid C., additional, Weyerer, Veronika, additional, Grimm, Marc-Oliver, additional, Horstmann, Marcus, additional, Sjödahl, Gottfrid, additional, Höglund, Mattias, additional, Steiniche, Torben, additional, Mogensen, Karin, additional, de Reyniès, Aurélien, additional, Nawroth, Roman, additional, Jordan, Brian, additional, Lin, Xiaoqi, additional, Dragicevic, Dejan, additional, Ward, Douglas G., additional, Goel, Anshita, additional, Hurst, Carolyn D., additional, Raman, Jay D., additional, Warrick, Joshua I., additional, Segersten, Ulrika, additional, Sikic, Danijel, additional, van Kessel, Kim E.M., additional, Maurer, Tobias, additional, Meeks, Joshua J., additional, DeGraff, David J., additional, Bryan, Richard T., additional, Knowles, Margaret A., additional, Simic, Tatjana, additional, Hartmann, Arndt, additional, Zwarthoff, Ellen C., additional, Malmström, Per-Uno, additional, Malats, Núria, additional, Real, Francisco X., additional, and Dyrskjøt, Lars, additional

Published
2020
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18. Molecular Markers Increase Precision of the European Association of Urology Non-Muscle-Invasive Bladder Cancer Progression Risk Groups

Author

van Kessel, Kim E. M., van der Keur, Kirstin A., Dyrskjot, Lars, Algaba, Ferran, Welvaart, Naeromy Y. C., Beukers, Willemien, Segersten, Ulrika, Keck, Bastian, Maurer, Tobias, Simic, Tatjana, Horstmann, Marcus, Grimm, Marc-Oliver, Hermann, Gregers G., Mogensen, Karin, Hartmann, Arndt, Harving, Niels, Petersen, Astrid C., Jensen, Jorgen B., Junker, Kerstin, Boormans, Joost L., Real, Francisco X., Malats, Nuria, Malmström, Per-Uno, Orntoft, Torben F., Zwarthoff, Ellen C., van Kessel, Kim E. M., van der Keur, Kirstin A., Dyrskjot, Lars, Algaba, Ferran, Welvaart, Naeromy Y. C., Beukers, Willemien, Segersten, Ulrika, Keck, Bastian, Maurer, Tobias, Simic, Tatjana, Horstmann, Marcus, Grimm, Marc-Oliver, Hermann, Gregers G., Mogensen, Karin, Hartmann, Arndt, Harving, Niels, Petersen, Astrid C., Jensen, Jorgen B., Junker, Kerstin, Boormans, Joost L., Real, Francisco X., Malats, Nuria, Malmström, Per-Uno, Orntoft, Torben F., and Zwarthoff, Ellen C.

Abstract

Purpose: The European Association of Urology (EAU) guidelines for non-muscle-invasive bladder cancer (NMIBC) recommend risk stratification based on clinicopathologic parameters. Our aim was to investigate the added value of biomarkers to improve risk stratification of NMIBC. Experimental Design: We prospectively included 1,239 patients in follow-up for NMIBC in six European countries. Fresh-frozen tumor samples were analyzed for GATA2, TBX2, TBX3, and ZIC4 methylation and FGFR3, TERT, PIK3CA, and RAS mutation status. Cox regression analyses identified markers that were significantly associated with progression to muscle-invasive disease. The progression incidence rate (PIR = rate of progression per 100 patient-years) was calculated for subgroups. Results: In our cohort, 276 patients had a low, 273 an intermediate, and 555 a high risk of tumor progression based on the EAU NMIBC guideline. Fifty-seven patients (4.6%) progressed to muscle-invasive disease. The limited number of progressors in this large cohort compared with older studies is likely due to improved treatment in the past two decades. Overall, wild-type FGFR3 and methylation of GATA2 and TBX3 were significantly associated with progression (HR = 0.34, 2.53, and 2.64, respectively). The PIR for EAU high-risk patients was 4.25. On the basis of FGFR3 mutation status and methylation of GATA2, this cohort could be reclassified into a good class (PIR = 0.86, 26.2% of patients), a moderate class (PIR = 4.32, 49.7%), and a poor class (PIR = 7.66, 24.0%). Conclusions: We conclude that the addition of selected biomarkers to the EAU risk stratification increases its accuracy and identifies a subset of NMIBC patients with a very high risk of progression. (C) 2018 AACR.

Published
2018
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19. Molecular Markers Increase Precision of the European Association of Urology Non–Muscle-Invasive Bladder Cancer Progression Risk Groups

Author

van Kessel, Kim E.M., primary, van der Keur, Kirstin A., additional, Dyrskjøt, Lars, additional, Algaba, Ferran, additional, Welvaart, Naeromy Y.C., additional, Beukers, Willemien, additional, Segersten, Ulrika, additional, Keck, Bastian, additional, Maurer, Tobias, additional, Simic, Tatjana, additional, Horstmann, Marcus, additional, Grimm, Marc-Oliver, additional, Hermann, Gregers G., additional, Mogensen, Karin, additional, Hartmann, Arndt, additional, Harving, Niels, additional, Petersen, Astrid C., additional, Jensen, Jørgen B., additional, Junker, Kerstin, additional, Boormans, Joost L., additional, Real, Francisco X., additional, Malats, Núria, additional, Malmström, Per-Uno, additional, Ørntoft, Torben F., additional, and Zwarthoff, Ellen C., additional

Published
2018
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20. Prognostic Impact of a 12-gene Progression Score in Non-muscle-invasive Bladder Cancer : A Prospective Multicentre Validation Study

Author

Dyrskjot, Lars, Reinert, Thomas, Algaba, Ferran, Christensen, Emil, Nieboer, Daan, Hermann, Gregers G., Mogensen, Karin, Beukers, Willemien, Marquez, Mirari, Segersten, Ulrika, Hoyer, Soren, Ulhoi, Benedicte P., Hartmann, Arndt, Stohr, Robert, Wach, Sven, Nawroth, Roman, Schwamborn, Kristina, Tulic, Cane, Simic, Tatjana, Junker, Kerstin, Harving, Niels, Petersen, Astrid C., Jensen, Jorgen B., Keck, Bastian, Grimm, Marc-Oliver, Horstmann, Marcus, Maurer, Tobias, Steyerberg, Ewout W., Zwarthoff, Ellen C., Real, Francisco X., Malats, Nuria, Malmström, Per-Uno, Orntoft, Torben F., Dyrskjot, Lars, Reinert, Thomas, Algaba, Ferran, Christensen, Emil, Nieboer, Daan, Hermann, Gregers G., Mogensen, Karin, Beukers, Willemien, Marquez, Mirari, Segersten, Ulrika, Hoyer, Soren, Ulhoi, Benedicte P., Hartmann, Arndt, Stohr, Robert, Wach, Sven, Nawroth, Roman, Schwamborn, Kristina, Tulic, Cane, Simic, Tatjana, Junker, Kerstin, Harving, Niels, Petersen, Astrid C., Jensen, Jorgen B., Keck, Bastian, Grimm, Marc-Oliver, Horstmann, Marcus, Maurer, Tobias, Steyerberg, Ewout W., Zwarthoff, Ellen C., Real, Francisco X., Malats, Nuria, Malmström, Per-Uno, and Orntoft, Torben F.

Abstract

Background: Progression of non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) is life-threatening and cannot be accurately predicted using clinical and pathological risk factors. Biomarkers for stratifying patients to treatment and surveillance are greatly needed. Objective: To validate a previously developed 12-gene progression score to predict progression to MIBC in a large, multicentre, prospective study. Design, setting, and participants: We enrolled 1224 patients in ten European centres between 2008 and 2012. A total of 750 patients (851 tumours) fulfilled the inclusion and sample quality criteria for testing. Patients were followed for an average of 28 mo (range 0-76). A 12-gene real-time qualitative polymerase chain reaction assay was performed for all tumours and progression scores were calculated using a predefined formula and cut-off values. Outcome measurements and statistical analysis: We measured progression to MIBC using Cox regression analysis and log-rank tests for comparing survival distributions. Results and limitations: The progression score was significantly (p < 0.001) associated with age, stage, grade, carcinoma in situ, bacillus Calmette-Guerin treatment, European Organisation for Research and Treatment of Cancer risk score, and disease progression. Univariate Cox regression analysis showed that patients molecularly classified as high risk experienced more frequent disease progression (hazard ratio 5.08, 95% confidence interval 2.2-11.6; p < 0.001). Multivariable Cox regression models showed that the progression score added independent prognostic information beyond clinical and histopathological risk factors (p < 0.001), with an increase in concordance statistic from 0.82 to 0.86. The progression score showed high correlation (R-2 = 0.85) between paired fresh-frozen and formalin-fixed paraffin-embedded tumour specimens, supporting translation potential in the standard clinical setting. A limitation was

Published
2017
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21. Prognostic Impact of a 12-gene Progression Score in Non–muscle-invasive Bladder Cancer: A Prospective Multicentre Validation Study

Author

Dyrskjøt, Lars, primary, Reinert, Thomas, additional, Algaba, Ferran, additional, Christensen, Emil, additional, Nieboer, Daan, additional, Hermann, Gregers G., additional, Mogensen, Karin, additional, Beukers, Willemien, additional, Marquez, Mirari, additional, Segersten, Ulrika, additional, Høyer, Søren, additional, Ulhøi, Benedicte P., additional, Hartmann, Arndt, additional, Stöhr, Robert, additional, Wach, Sven, additional, Nawroth, Roman, additional, Schwamborn, Kristina, additional, Tulic, Cane, additional, Simic, Tatjana, additional, Junker, Kerstin, additional, Harving, Niels, additional, Petersen, Astrid C., additional, Jensen, Jørgen B., additional, Keck, Bastian, additional, Grimm, Marc-Oliver, additional, Horstmann, Marcus, additional, Maurer, Tobias, additional, Steyerberg, Ewout W., additional, Zwarthoff, Ellen C., additional, Real, Francisco X., additional, Malats, Núria, additional, Malmström, Per-Uno, additional, and Ørntoft, Torben F., additional

Published
2017
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25. Less extensive surgery compared to extensive surgery: survival seems similar in young women with adult ovarian granulosa cell tumor.

Author

Lauszus FF, Petersen AC, Neumann G, Cleemann L, Rosgaard A, Jørgensen A, Vandborg M, and Jakobsen A

Subjects
Adolescent, Adult, Age Distribution, Age Factors, Aged, Aged, 80 and over, Child, Child, Preschool, Denmark epidemiology, Female, Follow-Up Studies, Granulosa Cell Tumor epidemiology, Granulosa Cell Tumor pathology, Humans, Hysterectomy, Incidence, Infant, Infant, Newborn, Menopause, Middle Aged, Neoplasm Recurrence, Local mortality, Neoplasm Staging, Ovarian Neoplasms epidemiology, Ovarian Neoplasms pathology, Ovariectomy, Retrospective Studies, Salpingectomy, Survival Rate, Young Adult, Granulosa Cell Tumor surgery, Neoplasm Recurrence, Local surgery, Ovarian Neoplasms surgery
Abstract

Objective: To describe the outcome of adult granulosa cell tumor (AGCT) with respect to initial clinical findings, methods of surgery, and perioperative treatment., Study Design: Retrospective follow-up study., Setting: All hospitals in Jutland., Sample: 163 women diagnosed with AGCT., Methods: Follow-up by hospital data files, general practitioner, death certificate, and autopsy report. Revision of histopathology by a single pathologist., Main Outcome Measures: Survival and relapse by clinical data, stage, and type of surgery., Results: The incidence of AGCT was 1.37 per year per 100,000 women (95% CI: 1.08, 1.68). The median follow-up time was 15 years and for the 79 surviving women 22 years. Stage I was found in 94% of cases. Relapse occurred in 24% of women in stage I and 100% of the other stages. Survival in stage I was 95%, 89% and 84% after 5, 10 and 20 years respectively. Increased survival of stage I in postmenopausal women was associated with surgery including hysterectomy and bilateral oophorectomy (p<0.001). In women younger than 40 years no difference in survival was found due to type of surgery. Endometrial carcinoma was found 138 times (95% CI: 48, 275) more prevalent than the expected rate., Conclusion: The survival of women was better in AGCT than in epithelial ovarian tumor. Age and type of surgery, besides stage, influenced survival. Total abdominal hysterectomy and bilateral salpingo-oophorectomy is the recommended treatment with advancing age. At younger age less extensive surgery was associated with similar survival compared to extensive surgery, but with advancing age conservative surgery increased the risk of relapse and death., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Published
2014
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