Serum HER2 Level Measured by Dot Blot: A Valid and Inexpensive Assay for Monitoring Breast Cancer Progression

Li-Duan Tan,Ying Chen,Xiao-Qing Li,Yuan-Yuan Xu,Yu-Mei Feng,Yue Yu,Irina Lebedeva

doi:10.1371/journal.pone.0018764

Abstract

Human epidermal growth factor receptor 2 (HER2) is one of the most important prognostic and predictive factors for breast cancer patients. Recently, serum HER2 ECD level of patients detected by enzyme-linked immunoabsorbent assay (ELISA) has been shown to predict tumor HER2 status and reveal its association with tumor progression, recurrence and poor prognosis. In this study, we established a new method, dot blot assay, to measure the serum HER2 level in breast cancer patients and further to evaluate the clinical value for monitoring breast cancer progression. We found that the serum HER2 level measured by dot blot assay was significantly correlated with tissue HER2 status in breast cancer patients (P = 0.001), and also significantly correlated with HER2 level measured by ELISA (P = 1.06×10−11). Compared with ELISA method, the specificity and sensitivity of dot blot assay were 95.3% and 65.0%, respectively. The serum HER2 levels of patients with grade III or ER-negative were higher than those with grade I–II (P = 0.004) and ER-positive (P = 0.033), respectively. Therefore, the novel dot blot method to detect serum HER2 level is a valid and inexpensive assay with potential application in monitoring breast cancer progression in clinical situations.

Highlights

Breast cancer is one of most common malignant tumors with the highest incidence and the second highest mortality among all malignant tumors in females [1]
Serum human epidermal growth factor receptor 2 (HER2) levels was detected by dot blot By dot blot assay, the concentration of serum HER2 in 133 breast cancer patients were determined to range from 0.7 ng/ml to 133.1 ng/ml, median 20.5 ng/ml (Fig. 2)
The serum HER2 levels detected by dot blot assay and tissue HER2 status examined by IHC were positively correlated in 126 primary breast cancer patients (Spearman’s rho = 0.301, P = 0.001; Table 1, Fig. 3A)

Summary

Introduction

Breast cancer is one of most common malignant tumors with the highest incidence and the second highest mortality among all malignant tumors in females [1]. Amplification of ERBB2 gene or overexpression of HER2 protein is one of the most important prognostic factors in breast cancer patients [3,6,7] HER2 has been a target for specific breast cancer treatment with the monoclonal antibody trastuzumab (HerceptinH) which was approved in 1998 by the United States Food and Drug Administration (FDA). The benefit of this particular therapy has been sufficiently confirmed in metastatic breast carcinomas [8]. Other therapeutic strategies have been developed recently to target the HER2 protein, such as the tyrosine kinase inhibitor lapatinib, which appears to have efficacy after failure of trastuzumab therapy [9]

Methods

Results

Conclusion