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

Abstract

PurposeDual-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.MethodsWe 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.ResultsCytoplasmic 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.ConclusionDUSP4 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.

Taxotere-induced elevated expression of IL8 in carcinoma-associated fibroblasts of breast invasive ductal cancer

“…Invasive ductal carcinoma represents 70-80% of all breast cancer cases, which are responsible for the majority of breast cancer fatalities. Though great progress has been made in understanding the tumorigenesis and development of breast cancer, problems surrounding treatment of these disease persist (3). As an important approach for breast cancer treatment, chemotherapy and neoadjuvant chemotherapy have already been challenged by drug resistance, even multi-drug resistance, with the underlying mechanisms remaining unclear (4).…”

Differential Roles for DUSP Family Members in Epithelial-to-Mesenchymal Transition and Cancer Stem Cell Regulation in Breast Cancer

“…In contrast, DUSP4 acts as a tumour suppressor, with low expression associated with increased tumour grade, recurrence, and poor prognosis in breast cancer patients [ 18 , 19 ]. However, DUSP4 has also been shown to be upregulated in malignant tissues [ 16 , 20 ]. Similar to DUSP1, DUSP6 is upregulated in HER2 + carcinomas; however, little is known about its expression in normal mammary tissue [ 21 , 22 ].…”

DUSP4/MKP2 overexpression is associated with BRAFV600E mutation and aggressive behavior of papillary thyroid cancer

“…Balko et al 27 reported that the activation of the MAPK pathway due to DUSP4 loss promotes cancer stem cell-like phenotype in basal-like breast cancer. By contrast, Kim et al 12 suggested that DUSP4 is frequently upregulated in breast malignancy and may be a marker of adverse prognosis. The effects of DUSP4 in cancer progression still remain a puzzle.…”

“… 7 – 9 However, there are some studies, by contrast, suggesting that the gain of DUSP4 expression plays a crucial role in cancer development and progression. 10 – 12 It is also interesting to note recent studies showing that DUSP4 is related to drug resistance in breast cancer patients following chemotherapy. 13 , 14 So far, the clinical significance and biological effects of DUSP4 have not been established in PTC.…”