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Open Access Research

Relationships between serum HER2 ECD, TIMP-1 and clinical outcomes in Taiwanese breast cancer

Hsiu-Pei Tsai12, Shin-Cheh Chen2, Huei-Tzu Chien3, Yi-Yin Jan2, Tzu-Chieh Chao2, Miin-Fu Chen2 and Ling-Ling Hsieh4*

Author Affiliations

1 Graduate Institute of Clinical Medical Sciences, Chang Gung University, Tao-Yuan, Taiwan

2 Department of General Surgery, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan

3 Graduate Institute of Biomedical Sciences, Chang Gung University, Tao-Yuan, Taiwan

4 Department of Public Health, Chang Gung University, Tao-Yuan, Taiwan

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World Journal of Surgical Oncology 2012, 10:42  doi:10.1186/1477-7819-10-42

Published: 17 February 2012

Abstract

Background

Serum levels of the extracellular domain of HER2/neu (HER2 ECD) have been demonstrated to be associated with clinical outcomes. A disintegrin and metalloproteinase-10, a sheddase of HER2/neu, can drive cancer progression and its activity is inhibited by tissue inhibitor of metalloproteinase-1 (TIMP-1). However, elevated TIMP-1 expression has been associated with a poor prognosis of breast cancer. Therefore, this study was performed to explore the relationships between serum HER2 ECD, TIMP-1 and clinical outcomes.

Methods

One hundred and eighty-five female breast cancer patients, who received curative mastectomy without neo-adjuvant chemotherapy at Chang-Gung Memorial Hospital, were recruited with informed consent for this study. Pre-operative serum levels of HER2 ECD and TIMP-1 were measured using an enzyme-linked immunosorbent assay.

Results

Twenty-three cases (12.4%) were classified HER2 ECD positive. HER2 ECD positivity was significantly associated with age, lymph node involvement, histological grade, estrogen receptor status, progesterone receptor status, tissue HER2/neu overexpression, and disease-free survival (DFS). In an age, stage, ER and HER2/neu status matched subgroup (N = 41), the serum level of TIMP-1 was significantly associated with HER2 ECD positivity and DFS.

Conclusions

A high serum TIMP-1 was significantly associated with HER2 ECD positivity and a poorer DFS among Taiwanese primary breast cancer patients with HER2 overexpression.

Keywords:
breast cancer; HER2 ECD; TIMP-1; enzyme-linked immunosorbent assay; prognosis