Molecular profiling identifies synchronous endometrial and ovarian cancers as metastatic endometrial cancer with favorable clinical outcome.

Autor: Reijnen C; Department of Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, The Netherlands.; Department of Obstetrics and Gynaecology, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands., Küsters-Vandevelde HVN; Department of Pathology, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands., Ligtenberg MJL; Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands., Bulten J; Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands., Oosterwegel M; Department of Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, The Netherlands., Snijders MPLM; Department of Obstetrics and Gynaecology, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands., Sweegers S; Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands., de Hullu JA; Department of Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, The Netherlands., Vos MC; Department of Obstetrics and Gynaecology, Elisabeth-TweeSteden Hospital, Tilburg, The Netherlands., van der Wurff AAM; Department of Pathology, Elisabeth-TweeSteden Hospital, Tilburg, The Netherlands., van Altena AM; Department of Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, The Netherlands., Eijkelenboom A; Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands., Pijnenborg JMA; Department of Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, The Netherlands.
Jazyk: angličtina
Zdroj: International journal of cancer [Int J Cancer] 2020 Jul 15; Vol. 147 (2), pp. 478-489. Date of Electronic Publication: 2020 Feb 18.
DOI: 10.1002/ijc.32907
Abstrakt: Synchronous primary endometrial and ovarian cancers (SEOs) represent 10% of all endometrial and ovarian cancers and are assumed to develop as independent entities. We investigated the clonal relationship between endometrial and ovarian carcinomas in a large cohort classified as SEOs or metastatic disease (MD). The molecular profiles were compared to The Cancer Genome Atlas (TCGA) data to explore primary origin. Subsequently, the molecular profiles were correlated with clinical outcome. To this extent, a retrospective multicenter study was performed comparing patients with SEOs (n = 50), endometrial cancer with synchronous ovarian metastasis (n = 19) and ovarian cancer with synchronous endometrial metastasis (n = 20). Targeted next-generation sequencing was used, and a clonality index was calculated. Subsequently, cases were classified as POLE mutated, mismatch repair deficient (MMR-D), TP53-wild-type or TP53-mutated. In 92% of SEOs (46/50), the endometrial and concurrent ovarian carcinoma shared at least one somatic mutation, with a clonality index above 0.95, supporting a clonal origin. The SEO molecular profiles showed striking similarities with the TCGA endometrial carcinoma set. SEOs behaved distinctly different from metastatic disease, with a superior outcome compared to endometrial MD cases (p < 0.001) and ovarian MD cases (p < 0.001). Classification according to the TCGA identified four groups with different clinical outcomes. TP53 mutations and extra-utero-ovarian disease were independent predictors for poor clinical outcome. Concluding, SEOs were clonally related in an overwhelming majority of cases and showed a favorable prognosis. Their molecular profile implied a primary endometrial origin. TP53 mutation and extra-utero-ovarian disease were independent predictors for outcome, and may impact adjuvant systemic treatment planning.
(© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
Databáze: MEDLINE
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