Geburtshilfe Frauenheilkd 2022; 82(10): e138-e139
DOI: 10.1055/s-0042-1756988
Abstracts | DGGG

MLH1 promoter hypermethylation in mismatch repair deficient endometrial cancer.Defining a new subgroup?

N Pauly
1   Evangelische Kliniken Essen-Mitte, Department of Gynecology and Gynecological Oncology, Essen, Deutschland
2   University Hospital LMU Munich, Department of Obstetrics and Gynecology, München, Deutschland
,
P Harter
1   Evangelische Kliniken Essen-Mitte, Department of Gynecology and Gynecological Oncology, Essen, Deutschland
,
F Heitz
1   Evangelische Kliniken Essen-Mitte, Department of Gynecology and Gynecological Oncology, Essen, Deutschland
3   Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department for Gynecology with the Center for Oncologic Surgery Charité Campus Virchow-Klinikum, Berlin, Deutschland
,
B Schömig-Markiefka
4   University Hospital Cologne, Department of Pathology, Köln, Deutschland
,
M Moubarak
1   Evangelische Kliniken Essen-Mitte, Department of Gynecology and Gynecological Oncology, Essen, Deutschland
,
A Traut
1   Evangelische Kliniken Essen-Mitte, Department of Gynecology and Gynecological Oncology, Essen, Deutschland
,
S Kaiser
1   Evangelische Kliniken Essen-Mitte, Department of Gynecology and Gynecological Oncology, Essen, Deutschland
,
B Ataseven
1   Evangelische Kliniken Essen-Mitte, Department of Gynecology and Gynecological Oncology, Essen, Deutschland
2   University Hospital LMU Munich, Department of Obstetrics and Gynecology, München, Deutschland
› Author Affiliations
› Further Information
Also available at
 
 

    Objective Nearly 30% of unselected endometrial cancer (EC) are mismatch repair deficient (MMRd).The majority resulting from epigenetic changes due to MLH1 promoter hypermethylation (MLH1-PM) and only a fraction from mutations in the Lynch genes (MLH1/MSH2/MSH6/PMS2).

    Since less is known about the clinical characteristics of MMRd tumors especially based on MLH1-PM we aimed at clarifying the clinical features of EC with MLH1-PM.

    Methods EC patients treated between 2015-2022 who underwent MMR(IHC) +/- MLH1-PM (PCR)-testing were included. Three groups where defined. A)MMR proficient(p) B) MMRd/MLH1-PM 3) “probable” Lynch (defined as MMRd not due to MLH1-PM).

    Results MMR-testing was performed in 337/365 cases (279 MMRp and 58 MMRd [17,2%]). 36 of 45 tumors with MLH1 +/- PMS2 deficiency had MLH1-PM analysis, identifying MLH1-PM in 28 (77.8%) and classifying 8 (22.2%) without PM as “probable” Lynch. MMRd tumors were detected at higher stages, more often showed angioinvasion and endometrioid subtype and less abnormal p53 expression compared to MMRp. Patients with MMRd/MLH1-PM more often had endometrioid histology (89% vs 76%), showed no abnormal p53 expression (0% vs 19%) compared to “probable” Lynch. 5-year PFS was 73, 81 and 100 months (p=0.343) for MMRp, MMRd/MLH1-PM, and “probable” Lynch patients, respectively.

    Conclusion Significant differences in clinical characteristics were detected between MMRd and MMRp tumors, as well as between MMRd tumors depending on MLH1-PM status. Thus, this analysis supports evidence of heterogeneity in MMRd tumors concerning prognosis.


    #

    Interessenkonflikt

    Ich erkläre als korrespondierender Autor, dass meine Koautoren mir mitgeteilt haben, dass sie während der letzten 3 Jahre keine wirtschaftlichen oder persönlichen Verbindungen im oben genannten Sinne hatten. Auch ich selbst hatte keine derartigen Verbindungen in den letzten 3 Jahren.

    Publication History

    Article published online:
    11 October 2022

    © 2022. Thieme. All rights reserved.

    Georg Thieme Verlag
    Rüdigerstraße 14, 70469 Stuttgart, Germany