J Breast Cancer.  2015 Mar;18(1):1-7. 10.4048/jbc.2015.18.1.1.

Clinicopathological Significance of Dual-Specificity Protein Phosphatase 4 Expression in Invasive Ductal Carcinoma of the Breast

• Kim H
• Jang SM
• Ahn H
• Sim J
• Yi K
• Chung Y
• Han H
• Rehman A
• Chung MS
• Jang K
• Paik SS

• KMID: 2286330
• DOI: http://doi.org/10.4048/jbc.2015.18.1.1

Abstract

PURPOSE
Dual-specificity protein phosphatase 4 (DUSP4), also known as mitogen-activated protein kinase phosphatase (MKP) 2 is a member of the inducible nuclear MKP group. The role of DUSP4 in cancer development and progression appears to vary with the type of malignancy. The purpose of this study was to investigate DUSP4 expression in a case series of invasive ductal carcinoma of the breast.
METHODS
We constructed tissue microarrays consisting of 16, 14, 47, and 266 cases of normal breast tissue, usual ductal hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma, respectively. DUSP4 expression was investigated by immunohistochemistry.
RESULTS
Cytoplasmic DUSP4 expression was observed. DUSP4 was more frequently expressed in malignant than in benign cases (p=0.024). The mean DUSP4 expression score was significantly higher in malignant tumors than in benign lesions (p=0.019). DUSP4 expression was significantly correlated with a larger tumor size (>2 cm, p=0.015). There was no significant correlation between overall survival or disease-free survival and DUSP4 expression in all 266 patients. We evaluated the impact of DUSP4 expression on the survival of 120 patients with T1-stage tumors. Interestingly, Kaplan-Meier survival curves revealed that DUSP4 expression had a significant effect on both overall patient survival (p=0.034, log-rank test) and disease-free survival (p=0.045, log-rank test). In early T-stage breast cancer, DUSP4 expression was associated with a worse prognosis.
CONCLUSION
DUSP4 is frequently upregulated in breast malignancy, and may play an important role in cancer development and progression. In addition, it may be a marker of adverse prognosis, especially in patients with early T1-stage cancer.

Keyword

Breast neoplasms; Dual-specificity phosphatase 4; Prognosis

MeSH Terms

Breast Neoplasms
Breast*
Carcinoma, Ductal*
Carcinoma, Intraductal, Noninfiltrating
Cytoplasm
Disease-Free Survival
Humans
Hyperplasia
Immunohistochemistry
Kaplan-Meier Estimate
Prognosis
Protein Kinases
Protein Kinases

Figure

• 

  Figure 1 Representative microphotographs of dual-specificity protein phosphatase 4 (DUSP4) immunostaining in invasive ductal carcinoma (×200). (A) Negative, (B) weak, (C) moderate, and (D) strong. The tumor cells showed cytoplasmic DUSP4 staining.

• 

  Figure 2 Mean dual-specificity protein phosphatase 4 (DUSP4) expression score. Mean DUSP4 expression score was significantly higher in malignant tumors than in benign lesions (Kruskal-Wallis test). NL=normal breast tissue; UDH=usual ductal hyperplasia; DCIS=ductal carcinoma in situ; IDC=invasive ductal carcinoma.

• 

  Figure 3 Cumulative overall and disease-free survival curves according to dual-specificity protein phosphatase 4 (DUSP4) expression. There was no significant difference of overall and disease-free survival in all 266 patients with invasive ductal carcinoma (A, B). However, there was significant difference of overall and disease-free survival in 120 patients with the T1-stage tumor (C, D) (Kaplan-Meier method with log-rank test).

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