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)
Authors:
Pavel Dundr 1; David Cibula 2; Martin Doležel 3; Pavel Fabian 4; Jindřich Fínek 5; Tomáš Jirásek 6; Radoslav Matěj 1,7,8; Luboš; Petruželka 9; Lukáš Rob 10; Aleš Ryška 11; Marián Švajdler 12,13; Vít Weinberger 14; Michal Zikán 15
Authors‘ workplace:
Ústav patologie 1. LF UK a VFN v Praze
1; Onkogynekologické centrum, Gynekologicko-porodnická klinika 1. LF UK a VFN v Praze
2; Onkologická Klinika LF Palackého univerzity a Fakultní nemocnice Olomouc
3; Oddělení onkologické patologie, Masarykův onkologický ústav
4; Onkologická a radioterapeutická klinika LF UK v Plzni a Fakultní nemocnice Plzeň
5; Oddělení patologie, centrum PATOS, Krajská nemocnice Liberec
6; Ústav patologie, 3. LF UK a FN Královské Vinohrady
7; Ústav patologie a molekulární medicíny, 3. LF UK a Fakultní Thomayerova nemocnice
8; Onkologická klinika 1. LF UK a VFN v Praze
9; Gynekologicko-porodnická klinika 3. LF UK a FN Královské Vinohrady
10; Fingerlandův ústav patologie, LF UK a FN Hradec Králové
11; Šiklův ústav patologie, LFUK v Plzni a Fakultní nemocnice Plzeň
12; Bioptická laboratoř, s. r. o., Plzeň
13; Gynekologicko-porodnická klinika, LF Masarykovy Univerzity, FN Brno
14; Gynekologicko-porodnická klinika 1. LF UK a FN Bulovka
15
Published in:
Čes.-slov. Patol., 57, 2021, No. 3, p. 181-187
Category:
Overview
Molecular classification of endometrial carcinoma is becoming an important part of the diagnostic process with direct therapeutic implications. Recent international guidelines, including the joint ESGO-ESTRO-ESP recommendation, include the molecular classification into standard diagnostic algorithms. Molecular testing of endometrial carcinomas is also recommended in the latest (5th) edition of the WHO classification of Female Genital Tumors. Due to the need to implement these recommendations in practice, representatives of four professional societies of Czech Medical Association of J. E. Purkyně (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) organized a meeting focused on this topic. The result of this meeting is a joint recommendation for molecular testing of endometrial carcinoma in routine diagnostic practice in the Czech Republic.
Keywords:
Endometrial carcinoma – molecular testing – FIELD – mismatch repair system –p53
Sources
1. Thomas S et al., Interobserver Variability in the Diagnosis of Uterine High-Grade Endometrioid Carcinoma. Arch Pathol Lab Med 2016 140(8): 836-843.
2. Gilks CB, Oliva E, Soslow RA. Poor interobserver reproducibility in the diagnosis of high- grade endometrial carcinoma. Am J Surg Pathol 2013; 37(6): 874-881.
3. Female Genital Tumours. 5 ed. WHO Classification of Tumours. 2020, Lyon: IARC Press. 631.
4. Concin N et al. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. Int J Gynecol Cancer 2021; 31(1): 12-39.
5. De Leo A, et al. ARID1A and CTNNB1/beta- Catenin Molecular Status Affects the Clinicopathologic Features and Prognosis of Endometrial Carcinoma: Implications for an Improved Surrogate Molecular Classification. Cancers (Basel), 2021; 13(5): 950.
6. Leon-Castillo A, et al. Interpretation of somatic POLE mutations in endometrial carcinoma. J Pathol 2020; 250(3): 323-335.
7. Luchini C, et al. ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach. Ann Oncol 2019; 30(8): 1232-1243.
8. Doghri R et al. Mismatch Repair Deficiency in Endometrial Cancer: Immunohistochemistry Staining and Clinical Implications. Appl Immunohistochem Mol Morphol 2019; 27(9): 678-682.
9. Chen W, Frankel W. A practical guide to biomarkers for the evaluation of colorectal cancer. Mod Pathol 2019; 32(Suppl 1): 1-15.
10. Stelloo E et al. Practical guidance for mismatch repair-deficiency testing in endometrial cancer. Ann Oncol 2017; 28(1): 96-102.
11. Umar A et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 2004; 96(4): 261-268.
12. Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecol Oncol 1983; 15(1): 10-17.
13. Cancer Genome Atlas Research et al. Integrated genomic characterization of endometrial carcinoma. Nature 2013; 497(7447): 67-73.
14. Talhouk A et al. A clinically applicable molecular- based classification for endometrial cancers. Br J Cancer 2015; 113(2): 299-310.
15. Talhouk A et al. Molecular classification of endometrial carcinoma on diagnostic specimens is highly concordant with final hysterectomy: Earlier prognostic information to guide treatment. Gynecol Oncol 2016; 143(1): 46-53.
16. Talhouk A et al. Confirmation of ProMisE: A simple genomics-based clinical classifier for endometrial cancer. Cancer 2017; 123(5): 802- 813.
17. Wortman BG et al. Molecular-integrated risk profile to determine adjuvant radiotherapy in endometrial cancer: Evaluation of the pilot phase of the PORTEC-4a trial. Gynecol Oncol 2018; 151(1): 69-75.
18. Wortman BG et al. Ten-year results of the PORTEC-2 trial for high-intermediate risk endometrial carcinoma: improving patient selection for adjuvant therapy. Br J Cancer 2018; 119(9): 1067-1074.
19. Stelloo E 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- 24.
20. Stelloo E et al. Refining prognosis and identifying targetable pathways for high-risk endometrial cancer; a TransPORTEC initiative. Mod Pathol 2015; 28(6): 836-44.
21. Plotkin A et al. Interlaboratory Concordance of ProMisE Molecular Classification of Endometrial Carcinoma Based on Endometrial Biopsy Specimens. Int J Gynecol Pathol 2019; 39(6): 537-545.
22. Parra-Herran C et al. Molecular-based classification algorithm for endometrial carcinoma categorizes ovarian endometrioid carcinoma into prognostically significant groups. Mod Pathol 2017; 30(12): 1748-1759.
23. Kommoss S 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.
24. Bosse T et al. Molecular Classification of Grade 3 Endometrioid Endometrial Cancers Identifies Distinct Prognostic Subgroups. Am J Surg Pathol 2018; 42(5): 561-568.
25 Soslow RA et al. Endometrial Carcinoma Diagnosis: Use of FIGO Grading and Genomic Subcategories in Clinical Practice: Recommendations of the International Society of Gynecological Pathologists. Int J Gynecol Pathol 2019; 38 Suppl 1: S64-S74.
26. Altrabulsi B et al. Undifferentiated carcinoma of the endometrium. Am J Surg Pathol 2005; 29(10): 1316-1321.
27. Silva EG, Deavers MT, Malpica A. Undifferentiated carcinoma of the endometrium: a review. Pathology 2007; 39(1): 134-138.
28. Espdinosa I et al. Undifferentiated and dedifferentiated endometrial carcinomas with POLE exonuclease domain mutations have a favorable prognosis. Am J Surg Pathol 2017; 41(8): 1121-1128.
29. Baniak N et al. Targeted Molecular and Immunohistochemical Analyses of Endometrial Clear Cell Carcinoma Show that POLE Mutations and DNA Mismatch Repair Protein Deficiencies Are Uncommon. Am J Surg Pathol 2019; 43(4): 531-537.
30. An HJ et al. Molecular characterization of uterine clear cell carcinoma. Mod Pathol 2004; 17(5): 530-537.
31. DeLair DF et al. The genetic landscape of endometrial clear cell carcinomas. J Pathol 2017; 243(2): 230-241.
32. Bae HS et al. Should endometrial clear cell carcinoma be classified as Type II endometrial carcinoma? Int J Gynecol Pathol 2015; 34(1): 74-84.
33. Fadare O et al. The clinicopathologic significance of p53 and BAF-250a (ARID1A) expression in clear cell carcinoma of the endometrium. Mod Pathol 2013; 26(8): 1101-1110.
34. Kommoss FK et al. L1CAM further stratifies endometrial carcinoma patients with no specific molecular risk profile. Br J Cancer 2018; 119(4): 480-486.
35. Kommoss F et al. L1CAM: amending the “low-risk” category in endometrial carcinoma. J Cancer Res Clin Oncol 2017; 143(2): 255-262.
36. Bosse T et al. L1 cell adhesion molecule is a strong predictor for distant recurrence and overall survival in early stage endometrial cancer: pooled PORTEC trial results. Eur J Cancer 2014; 50(15): 2602-2610.
37. Kim G et al. Nuclear β-catenin localization and mutation of the CTNNB1 gene: a context- dependent association. Mod Pathol 2018; 31(10): 1553-1559.
38. Klat J et al. L1CAM as a Negative Prognostic Factor in Endometrioid Endometrial Adenocarcinoma FIGO Stage IA-IB. Anticancer Res 2019; 39(1): 421-424.
39. Smogeli E et al. L1CAM as a prognostic marker in stage I endometrial cancer: a validation study. BMC Cancer 2016; 16: 596.
40. Hoang LN et al. Interobserver Agreement in Endometrial Carcinoma Histotype Diagnosis Varies Depending on The Cancer Genome Atlas (TCGA)-based Molecular Subgroup. Am J Surg Pathol 2017; 41(2): 245-252.
41. Bakhsh S et al. Histopathological features of endometrial carcinomas associated with POLE mutations: implications for decisions about adjuvant therapy. Histopathology 2016; 68(6): 916-924.
42. Hussein YR et al. Clinicopathological analysis of endometrial carcinomas harboring somatic POLE exonuclease domain mutations. Mod Pathol 2015; 28(4): 505-514.
43. Yano M et al. Impact of TP53 immunohistochemistry on the histological grading system for endometrial endometrioid carcinoma. Mod Pathol 2019; 32(7): 1023-1031.
44. Leon-Castillo A et al. Clinicopathological and molecular characterisation of ‘multiple- -classifier’ endometrial carcinomas. J Pathol 2020; 250(3): 312-322.
45. Petrelli F et al. Outcomes Following Immune Checkpoint Inhibitor Treatment of Patients With Microsatellite Instability-High Cancers: A Systematic Review and Meta-analysis. JAMA Oncol 2020; 6(7): 1068-1071.
46. Snowsill TM et al. Cost-effectiveness analysis of reflex testing for Lynch syndrome in women with endometrial cancer in the UK setting. PLoS One 2019; 14(8): e0221419.
47. Ryan N et al. Lynch syndrome screening in gynaecological cancers: results of an international survey with recommendations for uniform reporting terminology for mismatch repair immunohistochemistry results. Histopathology 2019; 75(6): 813-824.
48. Zeimet AG et al. AGO Austria recommendation on screening and diagnosis of Lynch syndrome (LS). Arch Gynecol Obstet 2017; 296(1): 123-127.
Labels
Anatomical pathology Forensic medical examiner ToxicologyArticle was published in
Czecho-Slovak Pathology
![Issue 3](https://www.prolekare.cz/media/cache/resolve/journal_issue/media/image_pdf/00ff8c97a9a7162bea1b0cc069be9996.jpeg)
2021 Issue 3
Most read in this issue
- Next generation sequencing – a science tool or routine pathology?
- 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)
- Doporučení pro testování PD-L1: metodika testování a reportování výsledků Verze_1 (17. 5. 2021)
- Review of tumor infiltrating lymphocytes assessment in breast cancer in routine diagnostic practice