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Virchows Archiv

, Volume 466, Issue 4, pp 415–422 | Cite as

Mutation profile and clinical outcome of mixed endometrioid-serous endometrial carcinomas are different from that of pure endometrioid or serous carcinomas

  • L. Coenegrachts
  • D. A. Garcia-Dios
  • J. Depreeuw
  • M. Santacana
  • S. Gatius
  • M. Zikan
  • P. Moerman
  • L. Verbist
  • D. Lambrechts
  • Xavier Matias-GuiuEmail author
  • Frédéric AmantEmail author
Original Article

Abstract

Clinical outcome of 23 patients with mixed endometrioid and serous endometrial carcinomas (mixed EEC-SC) was compared to that of pure endometrioid (EEC) and pure serous (SC) carcinomas. Hotspot mutation frequencies in KRAS, PIK3CA, PTEN, and TP53 and microsatellite instability (MSI) status were determined in mixed EEC-SC, as well as in their EEC and SC microdissected components separately, and alterations were compared to frequencies in pure EEC and SC. Relapse-free (RFS) and overall survival (OS) differed significantly between mixed EEC-SC and pure EEC and SC, revealing that outcome of mixed EEC-SCs was intermediate to that of pure EEC and pure SC. PTEN mutations were absent in pure SC, but occurred in 20 % of pure EEC, and 13 % of mixed EEC-SC. In contrast, TP53 mutations were more frequent in pure SC (17 %) and mixed EEC-SC (22 %) than in pure EEC (2 %). Mutations in mixed EEC-SC were shared by the two microdissected components in 30 %, whereas in 35 %, some mutations were component-specific. Mutation analysis confirms similarities between the EEC and SC components of mixed EEC-SC with pure EEC and pure SC, respectively. However, PTEN and KRAS mutations were more frequent in the SC component of mixed EEC-SC than in pure SC, while TP53 mutations were more frequent in the EEC component of mixed EEC-SC than in pure EEC. Presence of different clonal mutation pattern between EEC and SC components of mixed EEC-SC raises the possibility of divergent tumor heterogeneity or biclonal origin in some cases.

Keywords

Endometrial cancer Mixed endometrial carcinomas Mutation analysis Clinical outcome 

Notes

Acknowledgments

This work was supported by the Verelst Uterine Cancer Fund Leuven (VBL) and by a research grant of FWO Flanders (G.0827.13). This work is a result of collaboration within ENITEC (European Network for Individualised Treatment in Endometrial Cancer) as part of ESGO (European Society of Gynecological Oncology). L.C. is a postdoctoral fellow of FWO Flanders and F.A. is senior researcher for FWO Flanders.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

428_2015_1728_MOESM1_ESM.doc (108 kb)
Supplementary Table 1 Detailed overview of all detected mutations in separate components of mixed EEC-SC. When a mutation is detected, this is indicated with 1, wild-type is indicated with 0. Colors are used to differentiate between mutations that are present in both components (green), mutations only in EEC component (yellow) and mutations only in SC component (orange). (DOC 108 kb) (DOC 56 kb)
428_2015_1728_MOESM2_ESM.doc (56 kb)
Supplementary Table 2 Overview of MSI status of the separate components of the mixed EEC-SC. MSI status was determined using the 59-marker panel recently established by Zhao et al. (under revision). (DOC 56 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • L. Coenegrachts
    • 1
  • D. A. Garcia-Dios
    • 1
    • 2
  • J. Depreeuw
    • 1
    • 2
    • 3
  • M. Santacana
    • 4
  • S. Gatius
    • 4
  • M. Zikan
    • 5
  • P. Moerman
    • 6
  • L. Verbist
    • 1
  • D. Lambrechts
    • 2
    • 3
  • Xavier Matias-Guiu
    • 4
    • 9
    Email author
  • Frédéric Amant
    • 1
    • 7
    • 8
    Email author
  1. 1.Gynecologic Oncology, Department of OncologyKU LeuvenLeuvenBelgium
  2. 2.Laboratory for Translational Genetics, Vesalius Research Center, VIBKU LeuvenLeuvenBelgium
  3. 3.Vesalius Research Center, VIBLeuvenBelgium
  4. 4.Department of Pathology and Molecular Genetics and Research Laboratory, Hospital Universitari Arnau de VilanovaUniversity of Lleida, IRBLLEIDALleidaSpain
  5. 5.Gynecological Oncology Centre, Department of Obstetrics and Gynecology, First Faculty of Medicine and General University HospitalCharles University in PraguePragueCzech Republic
  6. 6.Department of PathologyUniversity Hospitals GasthuisbergLeuvenBelgium
  7. 7.Obstetrics & Gynecology, Division of Gynecologic OncologyUniversity Hospitals GasthuisbergLeuvenBelgium
  8. 8.Gynecologic OncologyUniversity Hospital LeuvenLeuvenBelgium
  9. 9.Pathology and Molecular GeneticsInstitut de Recerca Biomedica de LleidaLleidaSpain

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