Impact of genomic stability on protein expression in endometrioid endometrial cancer

被引:32
作者
Lomnytska, M. I. [1 ,2 ]
Becker, S. [2 ]
Gemoll, T. [2 ,3 ]
Lundgren, C. [4 ]
Habermann, J. [3 ]
Olsson, A.
Bodin, I.
Engstrom, U. [5 ]
Hellman, U. [5 ]
Hellman, K. [4 ]
Hellstrom, A-C [4 ]
Andersson, S. [1 ]
Mints, M. [1 ]
Auer, G. [2 ]
机构
[1] Karolinska Inst, Karolinska Univ Hosp, Dept Obstet & Gynaecol, SE-17176 Stockholm, Sweden
[2] Karolinska Inst, Karolinska Univ Hosp, Dept Pathol & Oncol, Unit Canc Prote, SE-17176 Stockholm, Sweden
[3] Univ Lubeck, Dept Surg, D-23538 Lubeck, Germany
[4] Karolinska Univ Hosp, Dept Gynaecol Oncol, SE-17176 Stockholm, Sweden
[5] Uppsala Univ, Ludwig Inst Canc Res Ltd, SE-75124 Uppsala, Sweden
基金
英国医学研究理事会; 瑞典研究理事会;
关键词
endometrioid endometrial cancer; genomic stability; marker protein patterns; atypical endometrioid hyperplasia; HEPATOCELLULAR-CARCINOMA; PROTEOMIC APPROACH; IDENTIFICATION; HYBRIDIZATION; BINDING; ADENOCARCINOMAS; INSTABILITY; PROGRESSION; METASTASIS; BIOMARKERS;
D O I
10.1038/bjc.2012.67
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:1297 / 1305
页数:9
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