#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

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: Dundr P. 1;  Cibula D. 2;  Doležel M. 3;  Fabián P. 4;  Fínek J. 5;  Jirásek T. 6;  Matěj R. 1,7,8;  Petruželka L. 9;  Rob L. 10;  Ryška A. 11;  Švajdler M. 12,13;  Weinberger V. 14;  Zikán M. 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 UP a FN Olomouc 3;  Oddělení onkologické patologie, MOÚ Brno 4;  Onkologická a radioterapeutická klinika LF UK a FN Plzeň 5;  Oddělení patologie, Centrum PATOS, Krajská nemocnice Liberec, a. s. 6;  Ústav patologie, 3. LF UK a FN Královské Vinohrady, Praha 7;  Ústav patologie a molekulární medicíny, 3. LF UK a FTN Praha 8;  Onkologická klinika 1. LF UK a VFN v Praze 9;  Gynekologicko-porodnická klinika 3. LF UK a FN Královské Vinohrady, Praha 10;  Fingerlandův ústav patologie, LF UK a FN Hradec Králové 11;  Šiklův ústav patologie, LF UK a FN Plzeň 12;  Bioptická laboratoř, s. r. o., Plzeň 13;  Gynekologicko-porodnická klinika LF MU a FN Brno 14;  Gynekologicko-porodnická klinika 1. LF UK a FN Bulovka, Praha 15
Published in: Ceska Gynekol 2021; 86(4): 264-272
Category:
doi: https://doi.org/10.48095/cccg2021264

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 recommendation of the European Society of Gynaecological Oncology, the European Society for Radiotherapy and Oncology and the European Society of Pathology include the molecular classification into standard dia­gnostic algorithms. Molecular testing of endometrial carcinomas is also recommended in the latest (5th edition) of the World Health Organization classification of female genital tumors. Due to the need to implement these recommendations in practice, representatives of four professional societies of the Czech Medical Association of J. E. Purkyně (the Czech Oncological Society, the Oncogynecological Section of the Czech Gynecological and Obstetrical Society, the Society of Radiation Oncology, Biology and Physics, and the Society of Czech Pathologists) organized a meeting focused on this topic. Recommendation for molecular testing of endometrial carcinoma in routine dia­gnostic practice in the Czech Republic.

Keywords:

Endometrial carcinoma – molecular testing – POLE (DNA polymerase epsilon) – mismatch repair system – p53


Sources

1. Thomas S, Hussein Y, Bandyopadhyay S et al. Interobserver variability in the dia­gnosis of uterine high-grade endometrioid carcinoma. Arch Pathol Lab Med 2016; 140 (8): 836–843. doi: 10.5858/arpa.2015-0220-OA.

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. doi: 10.1097/PAS.0b013e31827f576a.

3. Board WC. Female genital tumours. In: WHO classification of tumours. 5th ed. Lyon: IARC Press 2020.

4. 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 2021; 31 (1): 12–39. doi: 10.1136/ijgc-2020-002230.

5. De Leo A, de Biase D, Lenzi J 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. doi: 10.3390/cancers13050950.

6. León-Castillo A, Britton H, McConechy MK et al. Interpretation of somatic POLE mutations in endometrial carcinoma. J Pathol 2020; 250 (3): 323–335. doi: 10.1002/path.5372.

7. Luchini C, Bibeau F, Ligtenberg MJ 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. doi: 10.1093/annonc/mdz116.

8. Doghri R, Houcine Y, Boujelbène N et al. Mis­match repair deficiency in endometrial cancer: immunohistochemistry staining and clinical implications. Appl Immunohistochem Mol Morphol 2019; 27 (9): 678–682. doi: 10.1097/PAI.0000000000000641.

9. Chen W, Frankel WL. A practical guide to bio­markers for the evaluation of colorectal cancer. Mod Pathol 2019; 32 (Suppl 1): 1–15. doi: 10.1038/s41379-018-0136-1.

10. Stelloo E, Jansen AM, Osse EM et al. Practical guidance for mismatch repair-deficiency testing in endometrial cancer. Ann Oncol 2017; 28 (1): 96–102. doi: 10.1093/annonc/mdw542.

11. Umar A, Boland CR, Terdiman JP et al. Revised Bethesda guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 2004; 96 (4): 261–268. doi: 10.1093/jnci/djh034.

12. Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecol Oncol 1983; 15 (1): 10–17. doi: 10.1016/0090-8258 (83) 90111-7.

13. Kandoth C, Schultz N, Cherniack AD et al. Cancer Genome Atlas Research Network. Integrated genomic characterization of endometrial carcinoma. Nature 2013; 497 (7447): 67–73. doi: 10.1038/nature12113.

14. 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.

15. Talhouk A, Hoang LN, McConechy MK 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. doi: 10.1016/j.ygyno.2016.07.090.

16. Talhouk A, McConechy MK, Leung S et al. Confirmation of ProMisE: a simple, genomics-based clinical classifier for endometrial cancer. Cancer 2017; 123 (5): 802–813. doi: 10.1002/cncr.30496.

17. Wortman BG, Bosse T, Nout RA 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. doi: 10.1016/j.ygyno.2018.07.020.

18. Wortman BG, Creutzberg CL, Putter H 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. doi: 10.1038/s41416-018-0310-8.

19. 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.

20. Stelloo E, Bosse T, Nout RA et al. Refining prognosis and identifying targetable pathways for high-risk endometrial cancer; a TransPORTEC initiative. Mod Pathol 2015; 28 (6): 836–844. doi: 10.1038/modpathol.2015.43.

21. Plotkin A, Kuzeljevic B, De Villa V et al. Interlaboratory concordance of ProMisE molecular classification of endometrial carcinoma based on endometrial bio­psy specimens. Int J Gynecol Pathol 2020; 39 (6): 537–545. doi: 10.1097/PGP.0000000000000654.

22. Parra-Herran C, Lerner-Ellis J, Xu B et al. Molecular-based classification algorithm for endometrial carcinoma categorizes ovarian endometrioid carcinoma into prognostically significant groups. Mod Pathol 2017; 30 (12): 1748–1759. doi: 10.1038/modpathol.2017.81.

23. 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.

24. 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.0000000000001020.

25. Soslow RA, Tornos C, Park KJ 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. doi: 10.1097/PGP.0000000000000518.

26. Altrabulsi B, Malpica A, Deavers MT et al. Undifferentiated carcinoma of the endometrium. Am J Surg Pathol 2005; 29 (10): 1316–1321. doi: 10.1097/01.pas.0000171003.72352.9a.

27. Silva EG, Deavers MT, Malpica A. Undifferentiated carcinoma of the endometrium: a review. Pathology 2007; 39 (1): 134–138. doi: 10.1080/00313020601159494.

28. Espinosa I, Lee CH, D’Angelo E 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. doi: 10.1097/PAS.000000000000873.

29. Baniak N, Fadare O, Köbel M 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. doi: 10.1097/PAS.0000000000001209.

30. An HJ, Logani S, Isacson C et al. Molecular characterization of uterine clear cell carcinoma. Mod Pathol 2004; 17 (5): 530–537. doi: 10.1038/modpathol.3800057.

31. DeLair DF, Burke KA, Selenica P et al. The genetic landscape of endometrial clear cell carcinomas. J Pathol 2017; 243 (2): 230–241. doi: 10.1002/path.4947.

32. Bae HS, Kim H, Kwon SY et al. Should endometrial clear cell carcinoma be classified as Type II endometrial carcinoma? Int J Gynecol Pathol 2015; 34 (1): 74–84. doi: 10.1097/PGP.0000000000000111.

33. Fadare O, Gwin K, Desouki MM 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. doi: 10.1038/modpathol.2013.35.

34. Kommoss FK, Karnezis AN, Kommoss F et al. L1CAM further stratifies endometrial carcinoma patients with no specific molecular risk profile. Br J Cancer 2018; 119 (4): 480–486. doi: 10.1038/s41416-018-0187-6.

35. Kommoss F, Kommoss F, Grevenkamp F et al. L1CAM: amending the „low-risk“ category in endometrial carcinoma. J Cancer Res Clin Oncol 2017; 143 (2): 255–262. doi: 10.1007/s00432-016-2276-3.

36. Bosse T, Nout RA, Stelloo E 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. doi: 10.1016/j.ejca.2014.07.014.

37. Kim G, Kurnit KC, Djordjevic B et al. Nuclear b-catenin localization and mutation of the CTNNB1 gene: a context-dependent association. Mod Pathol 2018; 31 (10): 1553–1559. doi: 10.1038/s41379-018-0080-0.

38. Klat J, Mladenka A, Dvorackova J et al. L1CAM as a negative prognostic factor in endometrioid endometrial adenocarcinoma FIGO stage IA-IB. Anticancer Res 2019; 39 (1): 421–424. doi: 10.21873/anticanres.13128.

39. Smogeli E, Davidson B, Cvancarova M et al. L1CAM as a prognostic marker in stage I endometrial cancer: a validation study. BMC Cancer 2016; 16: 596. doi: 10.1186/s12885-016-2361-4.

40. Hoang LN, Kinloch MA, Leo JM 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. doi: 10.1097/PAS.0000000000000764.

41. Bakhsh S, Kinloch M, Hoang LN et al. Histopathological features of endometrial carcinomas associated with POLE mutations: implications for decisions about adjuvant therapy. Histopathology 2016; 68 (6): 916–924. doi: 10.1111/his.12878.

42. Hussein YR, Weigelt B, Levine DA et al. Clinicopathological analysis of endometrial carcinomas harboring somatic POLE exonuclease domain mutations. Mod Pathol 2015; 28 (4): 505–514. doi: 10.1038/modpathol.2014.143.

43. Yano M, Ito K, Yabuno A et al. Impact of TP53 immunohistochemistry on the histological grading system for endometrial endometrioid carcinoma. Mod Pathol 2019; 32 (7): 1023–1031. doi: 10.1038/s41379-019-0220-1.

44. León-Castillo A, Gilvazquez E, Nout R et al. Clinicopathological and molecular characterisation of ‚multiple-classifier‘ endometrial carcinomas. J Pathol 2020; 250 (3): 312–322. doi: 10.1002/path.5373.

45. Petrelli F, Ghidini M, Ghidini A 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. doi: 10.1001/jamaoncol.2020.1046.

46. Snowsill TM, Ryan NA, Crosbie EJ 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. doi: 10.1371/journal.pone.0221419.

47. Ryan N, Wall J, Crosbie EJ 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. doi: 10.1111/his.13925.

48. Zeimet AG, Mori H, Petru E et al. AGO Austria recommendation on screening and dia­gnosis of Lynch syndrome (LS). Arch Gynecol Obstet 2017; 296 (1): 123–127. doi: 10.1007/s00404-017-4392-y.

Labels
Paediatric gynaecology Gynaecology and obstetrics Reproduction medicine

Article was published in

Czech Gynaecology

Issue 4

2021 Issue 4

Most read in this issue
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#