Sara Imboden1, Denis Nastic2, Mehran Ghaderi2, Filippa Rydberg2, Franziska Siegenthaler1, Michael D Mueller1, Tilman T Rau3, Elisabeth Epstein4, Joseph W Carlson5. 1. Department of Obstetrics and Gynecology, Bern University Hospital and University of Bern, Bern, Switzerland. 2. Department of Oncology-Pathology, Karolinska Institutet, Department of Pathology and Cytology, Karolinska University Hospital, Stockholm, Sweden. 3. Institute of Pathology, University of Bern, Bern, Switzerland. 4. Department of Clinical Science and Education, Karolinska Institutet, Department of Obstetrics and Gynecology, Södersjukhuset, Stockholm, Sweden. 5. Department of Oncology-Pathology, Karolinska Institutet, Department of Pathology and Cytology, Karolinska University Hospital, Stockholm, Sweden. Electronic address: joseph.carlson@med.usc.edu.
Abstract
INTRODUCTION: In 2021, a joint ESGO/ESTRO/ESP committee updated their evidence-based guidelines for endometrial cancer, recommending a new risk grouping incorporating both clinicopathologic and molecular parameters. We applied the new risk grouping and compared the results to those of the prior 2016 clinicopathologic system. MATERIALS AND METHODS: We classified molecularly a cohort of 604 women diagnosed with endometrial cancer using immunohistochemistry for TP53 and MMR proteins on a tissue microarray, as well as Sanger sequencing for POLE mutations. These results, combined with clinicopathologic data, allowed the patients to be risk grouped using both the new 2021 molecular/clinicopathologic parameters and the prior 2016 clinicopathologic system. RESULTS: The application of the 2021 molecular markers shows Kaplan-Meier curves with a significant difference between the groups for all survival. Molecular classification under the 2021 guidelines revealed a total of 39 patients (39/594, 7%) with a change in risk group in relation to the 2016 classification system: the shift was alone due to either P53abn or POLEmut molecular marker. In order to ensure correct 2021 molecular risk classification, not all patients with endometrial cancer need a molecular diagnostic: 433 (72.9%) cases would need to be analyzed by TP53 IHC, only 46 (7.7%) by MMR IHC and 286 (48.1%) POLE sequencing reactions. CONCLUSION: Application of the 2021 molecular risk groups is feasible and shows significant differences in survival. IHC for TP53 and MMR and applying POLE sequencing is only needed in selected cases and leads to shifting risk groups both upward and downward for a sizeable number of patients. It is possible to significantly reduce the number of analyses required to implement the classification if resources are limited.
INTRODUCTION: In 2021, a joint ESGO/ESTRO/ESP committee updated their evidence-based guidelines for endometrial cancer, recommending a new risk grouping incorporating both clinicopathologic and molecular parameters. We applied the new risk grouping and compared the results to those of the prior 2016 clinicopathologic system. MATERIALS AND METHODS: We classified molecularly a cohort of 604 women diagnosed with endometrial cancer using immunohistochemistry for TP53 and MMR proteins on a tissue microarray, as well as Sanger sequencing for POLE mutations. These results, combined with clinicopathologic data, allowed the patients to be risk grouped using both the new 2021 molecular/clinicopathologic parameters and the prior 2016 clinicopathologic system. RESULTS: The application of the 2021 molecular markers shows Kaplan-Meier curves with a significant difference between the groups for all survival. Molecular classification under the 2021 guidelines revealed a total of 39 patients (39/594, 7%) with a change in risk group in relation to the 2016 classification system: the shift was alone due to either P53abn or POLEmut molecular marker. In order to ensure correct 2021 molecular risk classification, not all patients with endometrial cancer need a molecular diagnostic: 433 (72.9%) cases would need to be analyzed by TP53 IHC, only 46 (7.7%) by MMR IHC and 286 (48.1%) POLE sequencing reactions. CONCLUSION: Application of the 2021 molecular risk groups is feasible and shows significant differences in survival. IHC for TP53 and MMR and applying POLE sequencing is only needed in selected cases and leads to shifting risk groups both upward and downward for a sizeable number of patients. It is possible to significantly reduce the number of analyses required to implement the classification if resources are limited.
Authors: Eun Young Kang; Nicholas Jp Wiebe; Christa Aubrey; Cheng-Han Lee; Michael S Anglesio; Derek Tilley; Prafull Ghatage; Gregg S Nelson; Sandra Lee; Martin Köbel Journal: J Pathol Clin Res Date: 2021-10-01
Authors: Jorge Luis Ramon-Patino; Ignacio Ruz-Caracuel; Victoria Heredia-Soto; Luis Eduardo Garcia de la Calle; Bulat Zagidullin; Yinyin Wang; Alberto Berjon; Alvaro Lopez-Janeiro; Maria Miguel; Javier Escudero; Alejandro Gallego; Beatriz Castelo; Laura Yebenes; Alicia Hernandez; Jaime Feliu; Alberto Pelaez-García; Jing Tang; David Hardisson; Marta Mendiola; Andres Redondo Journal: Cancers (Basel) Date: 2022-02-12 Impact factor: 6.639
Authors: Tilman T Rau; Mona V Deppeler; Lucine Christe; Franziska Siegenthaler; Sara Imboden; Andrea Papadia; Michael D Mueller Journal: Virchows Arch Date: 2022-07-19 Impact factor: 4.535
Authors: Yi Chen; Shuwen You; Jie Li; Yifan Zhang; Georgia Kokaraki; Elisabeth Epstein; Joseph Carlson; Wen-Kuan Huang; Felix Haglund Journal: Front Immunol Date: 2022-01-07 Impact factor: 7.561