DJ-1 in endometrial cancer: a possible biomarker to improve differential diagnosis between subtypes

Int J Gynecol Cancer. 2014 May;24(4):649-58. doi: 10.1097/IGC.0000000000000102.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Clear Cell / diagnosis*
  • Adenocarcinoma, Clear Cell / metabolism
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Case-Control Studies
  • Cystadenocarcinoma, Serous / diagnosis*
  • Cystadenocarcinoma, Serous / metabolism
  • Endometrial Neoplasms / classification*
  • Endometrial Neoplasms / diagnosis*
  • Endometrial Neoplasms / metabolism
  • Endometrium / metabolism*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Oncogene Proteins / metabolism*
  • Prognosis
  • Protein Deglycase DJ-1

Substances

  • Biomarkers, Tumor
  • Intracellular Signaling Peptides and Proteins
  • Oncogene Proteins
  • PARK7 protein, human
  • Protein Deglycase DJ-1