Methylation profiles of endometrioid and serous endometrial cancers

Laura M.S. Seeber, Ronald P. Zweemer, Luigi Marchionni, Leon F.A.G. Massuger, Vincent T.H.B.M. Smit, W. Marchien Van Baal, René H.M. Verheijen, Paul J. Van Diest

Research output: Contribution to journalArticle

Abstract

Promoter methylation is a gene- and cancer type-specific epigenetic event that plays an important role in tumour development. As endometrioid (endometrioid endometrial carcinoma, EEC) and serous endometrial cancers (uterine papillary serous carcinoma, UPSC) exhibit different clinical, histological and molecular genetic characteristics, we hypothesized that these differences may be reflected in epigenetic phenomena as well. Identification of a panel of methylation biomarkers could be helpful in a correct histological classification of these two subtypes, which solely on the basis of morphology is not always easy. Methylation-specific multiplex ligation-dependent probe amplification was used to assess the extent of promoter methylation of different tumour suppressor genes in EEC and UPSC. Methylation results were correlated with histology and survival. The median cumulative methylation index of all genes was significantly higher in EEC (124) than in UPSC (93) (P<0.001). Promoter methylation of CDH13 and MLH1 was more frequently present in EEC, while CDKN2B and TP73 were more frequently methylated in UPSC. Almost 90% of EEC and 70% of UPSC could be predicted by CDH13 and TP73. In EEC, methylation of MLH1 was associated with a shorter disease-free survival (DFS; P<0.0001) and overall survival (OS; P=0.005). In a multivariate model, MLH1 methylation emerged as an additional prognostic factor to stage for DFS (P=0.002). In conclusion, promoter methylation is more common in EEC than UPSC. A panel of methylation biomarkers could be useful to distinguish between the two histological subtypes of endometrial cancer. Furthermore, methylation of MLH1 may have prognostic value in EEC.

Original languageEnglish (US)
Pages (from-to)663-673
Number of pages11
JournalEndocrine-related cancer
Volume17
Issue number3
DOIs
StatePublished - Sep 2010

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Cancer Research

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  • Cite this

    Seeber, L. M. S., Zweemer, R. P., Marchionni, L., Massuger, L. F. A. G., Smit, V. T. H. B. M., Van Baal, W. M., Verheijen, R. H. M., & Van Diest, P. J. (2010). Methylation profiles of endometrioid and serous endometrial cancers. Endocrine-related cancer, 17(3), 663-673. https://doi.org/10.1677/ERC-10-0014