Independent tissue-based biomarkers in endometrioid endometrial cancer

• Verfasst von: Stögbauer, Fabian [VerfasserIn]
• Verfasst von: Geß, Barbara [VerfasserIn]
• Verfasst von: Brambs, Christine [VerfasserIn]
• Verfasst von: Lautizi, Manuela [VerfasserIn]
• Verfasst von: Kacprowski, Tim [VerfasserIn]
• Verfasst von: Ourailidis, Iordanis [VerfasserIn]
• Verfasst von: Bronger, Holger [VerfasserIn]
• Verfasst von: Kiechle, Marion [VerfasserIn]
• Verfasst von: Noske, Aurelia [VerfasserIn]
• Verfasst von: Keller, Gisela [VerfasserIn]
• Verfasst von: Jesinghaus, Moritz [VerfasserIn]
• Verfasst von: Poremba, Christopher [VerfasserIn]
• Verfasst von: Weichert, Wilko [VerfasserIn]
• Verfasst von: Boxberg, Melanie [VerfasserIn]
• Titel: Independent tissue-based biomarkers in endometrioid endometrial cancer
• Titelzusatz: tumor budding in microsatellite instability and WHO grading in copy-number-low patients
• Verf.angabe: Fabian Stögbauer, Barbara Geß, Christine Brambs, Manuela Lautizi, Tim Kacprowski, Iordanis Ourailidis, Holger Bronger, Marion Kiechle, Aurelia Noske, Gisela Keller, Moritz Jesinghaus, Christopher Poremba, Wilko Weichert and Melanie Boxberg
• Jahr: 2023
• Umfang: 19 S.
• Illustrationen: Illustrationen
• Fussnoten: Veröffentlicht: 28. Juli 2023 ; Gesehen am 09.10.2023
• Titel Quelle: Enthalten in: Cancers
• Ort Quelle: Basel : MDPI, 2009
• Jahr Quelle: 2023
• Band/Heft Quelle: 15(2023), 15, Artikel-ID 3832, Seite 1-19
• ISSN Quelle: 2072-6694
• DOI: doi:10.3390/cancers15153832
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: CN-low
• Sach-SW: endometrial cancer
• Sach-SW: lymph node metastasis
• Sach-SW: molecular subtypes
• Sach-SW: MSI
• Sach-SW: prognosis
• Sach-SW: tissue based biomarkers
• Sach-SW: tumor budding
• K10plus-PPN: 1860954065

Abstract

The molecular characterization of endometrial endometrioid adenocarcinomas has provided major advances in its prognostic stratification. However, risk assessment of microsatellite instability (MSI) and copy-number (CN)-low cases remains a challenge. Thus, we aimed to identify tissue-based morphologic biomarkers that might help in the prognostic stratification of these cases. Histomorphologic parameters (WHO grading, tumor budding (TB), tumor-stroma ratio (as a quantitative description of stromal desmoplasia), tumor-infiltrating lymphocytes (TIL), “microcystic, elongated, fragmented” (MELF) pattern) were analyzed in resection specimens of the TCGA-UCEC cohort (n = 228). For each quantitative parameter, a two-tiered system was developed utilizing systematically determined cutoffs. Associations with survival outcomes were calculated in univariate and multivariate analysis and validated in two independent cohorts. In MSI tumors, only TB remained an independent prognostic factor. TB (≥3 buds/high-power field) was associated with inferior outcomes and with lymph node metastases. The prognostic significance of TB was confirmed in two validation cohorts. For CN-low tumors, established grading defined by the WHO was independently prognostic with inferior outcomes for high-grade tumors. The evaluation of TB might help in identifying MSI-patients with unfavorable prognosis who, e.g., could benefit from lymphadenectomy. WHO-based grading facilitates independent prognostic stratification of CN-low endometrioid adenocarcinomas. Therefore, we propose the utilization of TB and WHO-based grading, two tissue-based and easy-to-assess biomarkers, in MSI/CN-low endometrial carcinomas for improved clinical management.