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Kang, Cho, Ha, and Kwon: Evaluation of Serum HER-2/neu Extracelluar Domain in Breast Cancer Patients: Correlation with Tissue HER-2/neu Status and Clinicopathological Factors
Original Article
Journal of the Korean Surgical Society

Journal of the Korean Surgical Society 2010; 78(5): 271-276.

Published online: 10 May 2010

DOI: https://doi.org/10.4174/jkss.2010.78.5.271

Evaluation of Serum HER-2/neu Extracelluar Domain in Breast Cancer Patients: Correlation with Tissue HER-2/neu Status and Clinicopathological Factors

Sun Hee Kang, M.D., Jihyoung Cho, M.D., Jung Sook Ha, M.D.1, Sun Young Kwon, M.D., Ph.D.2

Department of Surgery, Keimyung University School of Medicine, Daegu, Korea.

1Department of Laboratory Medicine, Keimyung University School of Medicine, Daegu, Korea.

2Department of Pathology, Keimyung University School of Medicine, Daegu, Korea.

Corresponding author (shkang9002@dsmc.or.kr)

Received 4 November 2009       Accepted 18 January 2010

Copyright © 2010 The Korean Surgical Society

Abstract

Purpose

The extracelluar domain (ECD) of HER2 may be cleaved from the surface of cancer cells whereby serum HER2 ECD levels can be detected. We explored the correlation between serum HER2 ECD and tissue HER2 status and their relationship with clinicopathological parameters.

Methods

We included 125 patients with stage 0-3 breast cancer. The serum HER2 ECD level was measured by chemiluminescence immunoassay (ADVIA Centaur® system). The tissue HER2 status was analyzed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in all tumors. We reviewed the medical records retrospectively. The analyzed clinicopathological parameters were age, tumor size, histologic grade, vascular invasion, lymph node involvement, stage, estrogen receptor (ER) and CA 15-3.

Results

High serum HER2 ECD levels (≥15 ng/ml) were reported in 15 patients (12.0%). For tissue HER 2 status, 30 patients (24.0%) had positive results in FISH and 46 patients (37.0%) had strong positive results in IHC (3+). The specificity of serum HER2 ECD was 92.6% but the sensitivity was only 26.7%. The concordance between serum HER2 ECD and FISH tests was 23.3%. High serum HER2 ECD levels were significantly associated with old age (P=0.005), large tumor size (P=0.021), vascular invasion (P=0.001), lymph node involvement (P=0.010) and advanced stage (P<0.001). ER and CA 15-3 levels were not significantly related with serum HER2 ECD.

Conclusion

Serum HER2 ECD test could not be substituted for tissue HER2 status because of low concordance. However, high levels of serum HER2 were associated with large tumor size, lymph node involvement and advanced stage. We need to study serum HER2 ECD test as a role of prognostic marker.

Keywords: Serum HER2 ECD, Immunohistochemistry, Fluorescence in situ hybridization, Breast cancer

Figures and Tables

Fig. 1
Distribution of serum HER2 ECD levels in breast cancer patients with FISH positive or FISH negative tissue. The horizontal line indicates the cut-off value of 15 ng/ml.
jkss-78-271-g001
Table 1
Patient's characteristics
jkss-78-271-i001

*LN = lymph node; †ER = estrogen receptor; ‡ECD = extracellular domain; §IHC = immunohistochemistry; ∥FISH = fluorescence in situ hybridization.

Table 2
Association between FISH* and IHC†
jkss-78-271-i002

*FISH = fluorescence in situ hybridization; †IHC = immunohistochemistry; P<0.001.

Table 3
Association between FISH* and serum HER2 ECD† levels
jkss-78-271-i003

Concordance 23.3%; P=0.005; *FISH = fluorescence in situ hybridization; †ECD = extracellular domain.

Table 4
Relationship between serum HER2 ECD* and clinicopathologic variables
jkss-78-271-i004

*ECD = extracellular domain, †LN = lymph node; ‡ER = estrogen receptor.

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