Vol 94, No 1 (2023)
Research paper
Published online: 2021-12-06

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Classification of high-grade endometrium carcinomas using molecular and immunohistochemical methods

Denizhan Bayramoglu1, Özlem Seçilmiş Kerimoğlu1, Zeynep Bayramoğlu2, Ersin Çintesun1, Gözde Şahin1, Pınar Karabağlı3, Çetin Çelik1
Pubmed: 35072228
Ginekol Pol 2023;94(1):3-11.


Objectives: As a result of the integration of molecular changes into the histological classification of cancers, which increases diagnostic repeatability, the differences between the groups become more prominent and targeted therapies gain significance. The most comprehensive molecular study regarding endometrial carcinomas (EC) is The Cancer Genome Atlas (TCGA) project. According to TCGA, endometrial carcinomas are classified into four molecular prognostic subgroups: copy-number-low/p53-wild-type (p53wt), DNA polymerase epsilon (POLE)-mutated/ultramutated (POLEmt), microsatellite-instability/hypermutated (MSI), and copy-number-high/p53-mutated (p53mt). In this study, we aim to apply the molecular classification to our high-grade endometrial cancer patients, and particularly, to identify our overtreated patients. Material and methods: Ninety-seven patients diagnosed with high-grade EC in Selcuk University, Faculty of Medicine between 2009-2018 were retrospectively evaluated and classified into four subgroups. Primary outcomes of overall and progression-free survival were evaluated for clinical, pathological, and molecular features. Further, all molecular groups were divided into endometroid and non-endometrioid groups, and disease-free survival (DFS) and overall survival (OS) were investigated across groups. Results: According to molecular classification, 23 patients (23.7%) were assigned to the MSI group, 21 (21.6%) to the POLEmt group, 40 (41.2%) to the p53mt group, and 13 (13.4%) to the p53wt group. Patients' DFS (p = 0.001) and OS rates (p = 0.001) were significantly different according to their molecular classification. The results of our analyses determined that, in the molecular classification of high-grade ECs, the p53mt group had the poorest prognosis and the POLEmt group had the best prognosis. Tumor size, myometrial invasion, lymphovascular space invasion (LVSI), lymph node metastasis, cervical invasion, ovarian invasion and stage showed statistically significant differences based on molecular classification (p < 0.05). Conclusions: The use of molecular classification in the clinical practice will allow more accurate prognostic prediction and more appropriate treatment planning, particularly as high-grade ECs constitute a heterogenous group with poor prognosis.

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  1. Miller KD, Siegel RL, Lin CC, et al. Cancer statistics, 2016. CA Cancer J Clin. 2016; 66(1): 7–30.
  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. 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.
  4. 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.
  5. Cosgrove CM, Tritchler DL, Cohn DE, et al. An NRG Oncology/GOG study of molecular classification for risk prediction in endometrioid endometrial cancer. Gynecol Oncol. 2018; 148(1): 174–180.
  6. 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.
  7. Proctor L, Pradhan M, Leung S, et al. Assessment of DNA Ploidy in the ProMisE molecular subgroups of endometrial cancer. Gynecol Oncol. 2017; 146(3): 596–602.
  8. 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.
  9. 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.
  10. 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.
  11. DeSantis CE, Ma J, Gaudet MM, et al. Cancer statistics, 2019. CA Cancer J Clin. 2019; 69(1): 7–34.
  12. 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.
  13. McAlpine JN, Temkin SM, Mackay HJ. Endometrial cancer: Not your grandmother's cancer. Cancer. 2016; 122(18): 2787–2798.
  14. Guan H, Semaan A, Bandyopadhyay S, et al. Prognosis and reproducibility of new and existing binary grading systems for endometrial carcinoma compared to FIGO grading in hysterectomy specimens. Int J Gynecol Cancer. 2011; 21(4): 654–660.
  15. Bendifallah S, Canlorbe G, Collinet P, et al. Just how accurate are the major risk stratification systems for early-stage endometrial cancer? Br J Cancer. 2015; 112(5): 793–801.
  16. Murali R, Soslow RA, Weigelt B. Classification of endometrial carcinoma: more than two types. Lancet Oncol. 2014; 15(7): e268–e278.
  17. 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.
  18. Nelson BH, McAlpine JN. The more tumors change, the more they stay tame: do T cells keep POLE ultramutated endometrial carcinomas in check? Gynecol Oncol. 2015; 138(1): 1–2.
  19. Briggs S, Tomlinson I. Germline and somatic polymerase ε and δ mutations define a new class of hypermutated colorectal and endometrial cancers. J Pathol. 2013; 230(2): 148–153.
  20. McAlpine J, Leon-Castillo A, Bosse T. The rise of a novel classification system for endometrial carcinoma; integration of molecular subclasses. J Pathol. 2018; 244(5): 538–549.
  21. Karnezis AN, Hoang LN, Coatham M, et al. Loss of switch/sucrose non-fermenting complex protein expression is associated with dedifferentiation in endometrial carcinomas. Mod Pathol. 2016; 29(3): 302–314.
  22. Travaglino A, Raffone A, Stradella C, et al. Impact of endometrial carcinoma histotype on the prognostic value of the TCGA molecular subgroups. Arch Gynecol Obstet. 2020; 301(6): 1355–1363.
  23. Meng Bo, Hoang LN, McIntyre JB, et al. POLE exonuclease domain mutation predicts long progression-free survival in grade 3 endometrioid carcinoma of the endometrium. Gynecol Oncol. 2014; 134(1): 15–19.