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Impact of genomic stability on protein expression in endometrioid endometrial cancer
Department of Obstetrics and Gynaecology, Karolinska University Hospital, Solna, Karolinska Institute, SE-17176 Stockholm, Sweden.
Unit of Cancer Proteomics, Department of Oncology and Pathology, Karolinska Institute, Karolinska University Hospital, SE-17176 Stockholm, Sweden.
Unit of Cancer Proteomics, Department of Oncology and Pathology, Karolinska Institute, Karolinska University Hospital, SE-17176 Stockholm, Sweden.
Department of Gynaecological Oncology, Radiumhemmet, Karolinska University Hospital, Solna, SE-17176 Stockholm, Sweden.
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2012 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 106, no 7, 1297-1305 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Genomic stability is one of the crucial prognostic factors for patients with endometrioid endometrial cancer (EEC). The impact of genomic stability on the tumour tissue proteome of EEC is not yet well established.

METHODS: Tissue lysates of EEC, squamous cervical cancer (SCC), normal endometrium and squamous cervical epithelium were subjected to two-dimensional (2D) gel electrophoresis and identification of proteins by MALDI TOF MS. Expression of selected proteins was analysed in independent samples by immunohistochemistry.

RESULTS: Diploid and aneuploid genomically unstable EEC displayed similar patterns of protein expression. This was in contrast to diploid stable EEC, which displayed a protein expression profile similar to normal endometrium. Approximately 10% of the differentially expressed proteins in EEC were specific for this type of cancer with differential expression of other proteins observed in other types of malignancy (e.g., SCC). Selected proteins differentially expressed in 2D gels of EEC were further analysed in an EEC precursor lesion, that is, atypical hyperplasia of endometrium, and showed increased expression of CLIC1, EIF4A1 and PRDX6 and decreased expression of ENO1, ANXA4, EMD and Ku70.

CONCLUSION: Protein expression in diploid and aneuploid genomically unstable EEC is different from the expression profile of proteins in diploid genomically stable EEC. We showed that changes in expression of proteins typical for EEC could already be detected in precursor lesions, that is, atypical hyperplasia of endometrium, highlighting their clinical potential for improving early diagnostics of EEC.

Place, publisher, year, edition, pages
2012. Vol. 106, no 7, 1297-1305 p.
Keyword [en]
endometrioid endometrial cancer, genomic stability, marker protein patterns, atypical endometrioid hyperplasia
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-173342DOI: 10.1038/bjc.2012.67ISI: 000302130700008OAI: oai:DiVA.org:uu-173342DiVA: diva2:517584
Available from: 2012-04-24 Created: 2012-04-23 Last updated: 2017-12-07Bibliographically approved

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