Clinical significance of DJ-1 as a secretory molecule: retrospective study of DJ-1 expression at mRNA and protein levels in ductal carcinoma of the breast

Benio Tsuchiya; Keiichi Iwaya; Norio Kohno; Takahiko Kawate; Tohru Akahoshi; Osamu Matsubara; Kiyoshi Mukai

doi:10.1111/j.1365-2559.2012.04202.x

Clinical significance of DJ-1 as a secretory molecule: retrospective study of DJ-1 expression at mRNA and protein levels in ductal carcinoma of the breast

Histopathology. 2012 Jul;61(1):69-77. doi: 10.1111/j.1365-2559.2012.04202.x. Epub 2012 Mar 2.

Authors

Benio Tsuchiya¹, Keiichi Iwaya, Norio Kohno, Takahiko Kawate, Tohru Akahoshi, Osamu Matsubara, Kiyoshi Mukai

Affiliation

¹ Division of Molecular Diagnostics, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Kanagawa, Japan. benio@med.kitasato-u.ac.jp

PMID: 22385318
DOI: 10.1111/j.1365-2559.2012.04202.x

Abstract

Aims: DJ-1 is a molecule secreted into serum by some breast cancer cells. However, little is known about the clinical significance of the DJ-1 expression.

Methods and results: Expression of DJ-1 protein was examined by immunohistochemistry, and expression of DJ-1 mRNA was detected using in-situ hybridization in 273 invasive ductal carcinomas (IDCs) and 41 ductal carcinomas in situ (DCISs) of the breast, and also in breast cancer cell lines. Breast cancer cells were examined for their secretion of DJ-1 using immunoblot analysis. By immunohistochemistry DJ-1 protein expression was lower than adjacent non-cancerous epithelium in 6 (14.6%) of the 41 DCISs and 146 (53%) of the 273 IDCs, even although all 314 carcinomas retained expression of DJ-1 mRNA, which was higher than that in adjacent non-cancerous epithelium in 220 cases (70%). Patients with IDC whose cancer cells showed low expression of DJ-1 protein had significantly shorter disease-free survival (P = 0.0152) and overall survival (P = 0.0196) than those whose cancer cells retained DJ-1 expression. MDA-MB-231 cells, which secreted DJ-1, showed low expression of DJ-1 protein.

Conclusions: Low expression of DJ-1 protein with high expression of its mRNA, which may reflect a secretory expression pattern, is predictive of poor outcome in patients with IDC.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Biomarkers, Tumor / metabolism*
Breast / metabolism
Breast / pathology
Breast Neoplasms / metabolism*
Breast Neoplasms / mortality
Breast Neoplasms / pathology
Carcinoma, Ductal, Breast / metabolism*
Carcinoma, Ductal, Breast / mortality
Carcinoma, Ductal, Breast / secondary
Carcinoma, Intraductal, Noninfiltrating / metabolism*
Carcinoma, Intraductal, Noninfiltrating / mortality
Carcinoma, Intraductal, Noninfiltrating / pathology
Carcinoma, Intraductal, Noninfiltrating / surgery
Female
Gene Expression Regulation, Neoplastic*
Humans
Intracellular Signaling Peptides and Proteins* / genetics
Intracellular Signaling Peptides and Proteins* / metabolism
Japan / epidemiology
Kaplan-Meier Estimate
Ki-67 Antigen / metabolism
Lymph Nodes / pathology
Lymphatic Metastasis
Mastectomy
Middle Aged
Neoplasm Staging
Oncogene Proteins* / genetics
Oncogene Proteins* / metabolism
Prognosis
Protein Deglycase DJ-1
RNA, Messenger / metabolism
Receptor, ErbB-2 / metabolism
Receptors, Estrogen / metabolism
Receptors, Progesterone / metabolism
Retrospective Studies
Survival Rate
Tissue Array Analysis
Young Adult

Substances

Biomarkers, Tumor
Intracellular Signaling Peptides and Proteins
Ki-67 Antigen
Oncogene Proteins
RNA, Messenger
Receptors, Estrogen
Receptors, Progesterone
ERBB2 protein, human
Receptor, ErbB-2
PARK7 protein, human
Protein Deglycase DJ-1