Molecular testing of endometrial carcinoma in real-world clinical practice
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‘ workplace:
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:
Klin Onkol 2023; 36(3): 215-223
Category:
Original Articles
doi:
https://doi.org/10.48095/ccko2023215
Overview
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
Sources
1. Modrá kniha České onkologické společnosti. [online]. Dostupné z: https: //www.linkos.cz/lekar-a-multidisciplinarni-tym/personalizovana-onkologie/modra-kniha-cos/aktualni-vydani-modre-knihy/.
2. Colombo N, Preti E, Landoni F et al. Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013; 24 (Suppl 6): vi33–vi38. doi: 10.1093/annonc/mdt353.
3. The Cancer Genome Atlas Research Network. Integrated genomic characterization of endometrial carcinoma. Nature 2013; 497 (7447): 67–73. doi: 10.1038/nature12113.
4. Talhouk A, McConechy MK, Leung S et al. A clinically applicable molecular-based classification for endometrial cancers. Br J Cancer 2015; 113 (2): 299–310. doi: 10.1038/bjc.2015.190.
5. León-Castillo A, de Boer SM, Powell ME et al. Molecular classification of the PORTEC-3 trial for high-risk endometrial cancer: impact on prognosis and benefit from adjuvant therapy. J Clin Oncol 2020; 38 (29): 3388–3397. doi: 10.1200/JCO.20.00549.
6. Stelloo E, Nout RA, Osse EM et al. Improved risk assessment by integrating molecular and clinicopathological factors in early-stage endometrial cancer-combined analysis of the PORTEC cohorts. Clin Cancer Res 2016; 22 (16): 4215–4224. doi: 10.1158/1078-0432.CCR-15-2878.
7. Kommoss S, McConechy MK, Kommoss F et al. Final validation of the ProMisE molecular classifier for endometrial carcinoma in a large population-based case series. Ann Oncol 2018; 29 (5): 1180–1188. doi: 10.1093/annonc/mdy058.
8. Concin N, Matias-Guiu X, Vergote I et al. ESGO/ ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. Int J Gynecol Cancer 2020; 31 (1): 12–39. doi: 10.1136/ijgc-2020-002230.
9. Dundr P, Cibula D, Doležel M et al. Molecular testing in endometrial carcinoma – joint recommendation of Czech Oncological Society, Oncogynecological Section of the Czech Gynecological and Obstetrical Society, Society of Radiation Oncology, Biology and Physics, and the Society of Czech Pathologists. Ceska Gynekol 2021; 86 (4): 264–272. doi: 10.48095/cccg2021264.
10. Talhouk A, McConechy MK, Leung S et al. Confirmation of ProMisE: a simple, genomics-based clinical classifier for endometrial cancer: molecular classification of EC. Cancer 2017; 123 (5): 802–813. doi: 10.1002/cncr.30496.
11. Bosse T, Nout RA, McAlpine JN et al. Molecular classification of grade 3 endometrioid endometrial cancers identifies distinct prognostic subgroups. Am J Surg Pathol 2018; 42 (5): 561–568. doi: 10.1097/PAS.0000000000001 020.
12. Devereaux KA, Weiel JJ, Pors J et al. Prospective molecular classification of endometrial carcinomas: institutional implementation, practice, and clinical experience. Mod Pathol 2022; 35 (5): 688–696. doi: 10.1038/s41379-021-00963-y.
13. Temko D, Van Gool IC, Rayner E et al. Somatic POLE exonuclease domain mutations are early events in sporadic endometrial and colorectal carcinogenesis, determining driver mutational landscape, clonal neoantigen burden and immune response. J Pathol 2018; 245 (3): 283–296. doi: 10.1002/path.5081.
14. Eggink FA, Mom CH, Boll D et al. Compliance with adjuvant treatment guidelines in endometrial cancer: room for improvement in high risk patients. Gynecol Oncol 2017; 146 (2): 380–385. doi: 10.1016/j.ygyno.2017.05.025.
15. Kurman RJ, Carcangiu ML, Herrington CS et al. WHO classification of tumours of female reproductive organs. International Agency for Research on Cancer 2014.
16. Brierley J, Gospodarowicz MK, Wittekind C et al. TNM klasifikace zhoubných novotvarů. [online]. Available from: https: //dwn.alza.cz/ebook/nahled/pdf2/EK34089.
17. Colombo N, Creutzberg C, Amant F et al. ESMO-ESGO-ESTRO consensus conference on endometrial cancer: diag- nosis, treatment and follow-up. Radiother Oncol 2015; 117 (3): 559–581. doi: 10.1016/j.radonc.2015.11.013.
Labels
Paediatric clinical oncology Surgery Clinical oncologyArticle was published in
Clinical Oncology
2023 Issue 3
Most read in this issue
- Waldenström’s macroglobulinemia – clinical symptoms and review of therapy yesterday, today and tomorrow
- Polygenic risk score (PRS) and its potential for breast cancer risk stratification
- Molecular testing of endometrial carcinoma in real-world clinical practice
- Hypoplastic form of myelodysplastic neoplasm