Molecular testing of endometrial carcinoma in real-world clinical practice

Česká verzia

Authors: Markéta Bednaříková ^1,2 ; J. Hausnerová ³; L. Minář ²; R. Taslerová ³; P. Vinklerová ²; L. Ehrlichová ¹; J. Trizuljak ^1,4; I. Blaháková ⁴; D. Princ ⁵; K. Matulová ³; P. Ovesná ⁶; O. Slabý ^3,4,7; V. Weinberger ²
Authors place of work: Interní hematologická a onkologická klinika LF MU a FN Brno ¹; Gynekologická a porodnická klinika LF MU a FN Brno ²; Ústav patologie, LF MU a FN Brno ³; CEITEC – Středoevropský technologický institut, MU Brno ⁴; Masarykův onkologický ústav, Brno ⁵; Institut biostatistiky a analýz, MU Brno ⁶; Ústav biologie, MU Brno ⁷
Published in the journal: Klin Onkol 2023; 36(3): 215-223
Category: Original Articles
doi: https://doi.org/10.48095/ccko2023215

Summary

Background: Molecular classification has brought significant changes in the management of endometrial cancer (EC). In this article, we aim to analyze our first experience with an implementation of molecular testing into daily clinical practice. Materials and methods: In all newly diagnosed EC, the status of mismatch repair (MMR) and p53 proteins has been evaluated immunohistochemically as a part of the routine histopathological examination since May 2021. In tumors that do not meet clinical criteria for a low risk and those with MMR deficiency or p53 mutation, the molecular genetic testing of the POLE gene is performed as well. Recommendations for adjuvant treatment or follow-up are subsequently made based on the risk of recurrence. Genetic counselling is proposed to all patients with MMR-deficient tumors or family history of cancer. Results: A total of 85 patients with newly diagnosed EC between May 2021 and May 2022 were enrolled in the analysis. The median age was 66 years. The results of molecular testing were as follows: 22 (26%) MMR-deficient, 8 (9%) p53-mutated and none POLE-ultramutated of those 40 tumors with performed POLE sequencing. A total of 46 (51%) patient had a low risk, 2 (2%) intermediate, 14 (16%) high-intermediate and 20 (24%) patients had a high risk of recurrence. Advanced or metastatic diseases were diagnosed in 6 (7%) patients. The median time between surgery and multidisciplinary tumor board decision was 21 days (8–36). A total of 76 (90%) patients underwent the whole treatment plan according to the recurrence risk. At the time of analysis, the results of genetic testing were available in 18 patients and revealed 4 (22%) carriers of a pathogenic variant in any of the genes associated with Lynch syndrome. Conclusion: Molecular testing combining immunohistochemical analyses of MMR and p53 proteins in all newly diagnosed EC patients with sequencing analysis of POLE in those with non-low-risk disease is feasible and does not prolong the time needed for treatment decision.

Keywords:

p53 – endometrial cancer – molecular testing – POLE – mismatch-repair system

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