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Basic Science
DJ-1 in Endometrial Cancer: A Possible Biomarker to Improve Differential Diagnosis Between Subtypes
  1. Michele Morelli, MD*,
  2. Domenica Scumaci, PhD†,
  3. Annalisa Di Cello, MD*,
  4. Roberta Venturella, MD*,
  5. Giuseppe Donato, MD, PhD‡,
  6. Maria Concetta Faniello, PhD†,
  7. Barbara Quaresima, PhD†,
  8. Giovanni Cuda, MD, PhD†,
  9. Fulvio Zullo, MD, PhD* and
  10. Francesco Costanzo, MD, PhD†
  1. *Unit of Obstetrics and Gynaecology, “Tommaso Campanella” Cancer Center of Germaneto, Department of Experimental and Clinical Medicine, ‘Magna Graecia’ University-Catanzaro, Italy;
  2. †Department of Experimental and Clinical Medicine, ‘Magna Graecia’ University-Catanzaro, Italy;
  3. ‡Unit of Pathology, Faculty of Medicine, Health Science Department, ‘Magna Graecia’ University-Catanzaro, Italy.
  1. Address correspondence and reprint requests to Annalisa Di Cello, MD, Unit of Obstetrics and Gynaecology, Department of Experimental and Clinical Medicine, ‘Magna Graecia’ University-Catanzaro, Italy, Viale Europa, Loc. Germaneto, 88100 Catanzaro, Italy.

Abstract

Objective The objectives of this study were to characterize the well-defined endometrial cancer (EC) type I (endometrioid [EEC] G1-G2) versus the prototype of EC type II (serous [ESC]) and to evaluate the expression of specific biomarkers differentially expressed between 2 well-defined types, in those EC subtypes (such as EEC G3) disputed between types I and II.

Methods Data from 25 patients (10 EEC G1-G2, 8 EEC G3, 5 ESC, and 2 clear cell) submitted to the surgical treatment were collected. Two-dimensional electrophoresis and mass spectrometry (MS) analysis were performed on 5 EEC G1-G2 and 5 healthy endometrial samples of the same patients. Differentially expressed proteins, such as DJ-1, were validated by Western blot. In patients with EEC G1-G2, serum levels of DJ-1, an overexpressed oncoprotein related to EC pathogenesis and progression, were evaluated and then compared with levels identified in patients with ESC and healthy controls. The DJ-1 immunohistochemical (IHC) staining was performed on neoplastic and healthy endometrium collected from the same patients. The 8 stored samples of EEC G3 were submitted to DJ-1 IHC assays.

Results The 2-dimensional electrophoresis analysis identified 1040 protein spots differentially expressed in EEC G1-G2 compared with healthy endometrium. Forty-two spots were subjected to liquid chromatography–MS/MS analysis. Thirty-three up-regulated (like an annexin 2 [ANXA2] shorter isoform, CAPG [macrophage-capping protein], DJ-1/PARK7) and 9 down-regulated (like calreticulin and ubiquitin carboxyl-terminal hydrolase isozyme L1) proteins were identified and validated by Western blot. A significant increase in serum DJ-1 levels of EEC G1-G2 versus the healthy controls and in ESC versus EEC patients was observed. DJ-1 IHC score was significantly higher in ESC versus those EEC G1-G2. In 3 cases of EEC G3, the DJ-1 expression was similar to the ESC subtype.

Conclusions The identification of proteins, such as DJ-1, differentially expressed, between well-defined EC types I and II allows to make a subtype-specific presurgical diagnosis and help surgeon to safely preoperatively choose a proper surgical treatment.

  • Endometrial cancer
  • DJ-1
  • ANXA2 shorter isoform
  • Subtype-specific diagnosis
  • Immunohistochemical profile

https://doi.org/10.1097/IGC.0000000000000102

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    Footnotes

    • M.M. and D.S. contributed equally to this work. F.Z. and F.C. contributed equally to this work.

    • This work was supported in part by grants from PON01-02834 Prometeo-Ricerca e Competitività 2007/2013.

    • The authors declare no conflicts of interest.

    • Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (www.ijgc.net).