Jung-Sun Lee; Won Ki Min; Eun Hwa Park; Woo-Sung Lim; Sung-Lim Choi; Byung-Ho Son; Sung-Bae Kim; Jin-Hee Ahn; Sei-Hyun Ahn

doi:10.4048/jbc.2008.11.3.116

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Lee, Min, Park, Lim, Choi, Son, Kim, Ahn, and Ahn: Correlation between the Her-2/neu Status as Determined by Immunohistochemical Analysis and the Serum Her-2/neu Concentration as Determined by the Use of ADVIA Cencaur® Automated Immunoassay in Breast Cancer Patients

Original Article

Journal of Breast Cancer

Journal of Breast Cancer 2008; 11(3): 116-124.

Published online: 30 September 2008

DOI: https://doi.org/10.4048/jbc.2008.11.3.116

Correlation between the Her-2/neu Status as Determined by Immunohistochemical Analysis and the Serum Her-2/neu Concentration as Determined by the Use of ADVIA Cencaur® Automated Immunoassay in Breast Cancer Patients

Jung-Sun Lee, Won Ki Min¹, Eun Hwa Park, Woo-Sung Lim, Sung-Lim Choi, Byung-Ho Son, Sung-Bae Kim², Jin-Hee Ahn², Sei-Hyun Ahn

Department of Surgery, University of Ulsan, College of Medicine and Asan Medical Center, Seoul, Korea.

¹Department of Laboratory Medicine, University of Ulsan, College of Medicine and Asan Medical Center, Seoul, Korea.

²Department of Oncology, University of Ulsan, College of Medicine and Asan Medical Center, Seoul, Korea.

ahnsh@amc.seoul.kr

Received 21 January 2008 Accepted 2 June 2008

Abstract

Purpose

Serum Her-2/neu is extracted from the extracelluar domain of the Her-2/neu tyrosine kinase to serum. We evaluated the correlation between the Her-2/neu status as determined by immunohistochemical analysis (IHC) and the serum Her-2/neu concentration in a population of Korean women with breast cancer.

Methods

Serum Her-2/neu levels were examined from 254 female patients with primary breast cancer and 38 patients with metastatic breast cancer. Serum Her-2/neu levels were measured by the use of a chemiluminescence immunoassay (ADVIA centaur® system) during the preoperative period. The level of Her-2/neu in all of the breast cancer tissue samples was determined by IHC, and samples with an IHC grade +2 were subject to fluorescence in situ (FISH). When tissue samples exhibited IHC grade +3 or showed amplification of Her-2/neu as determined by FISH analysis, Her-2/neu was considered overexpressed. The cut-off value for serum Her-2/neu level was 10.2 ng/mL.

Results

The mean serum Her-2/neu level was 10.1 ng/mL in primary breast cancer samples. The serum Her-2/neu concentration significantly correlated with expression of Her-2/neu as determined by tissue IHC analysis (grade 1/3, 9.33±1.7 ng/mL; grade 2/3, 8.89±1.6 ng/mL; grade 3/3, 12.37±4.0 ng/mL, p<0.001). Increased serum HER-2/neu levels were associated with the lymph node status (p=0.003) and hormone unresponsiveness (p<0.001), tumor size (p<0.01) and age group (p<0.001). In metastatic breast cancer samples, the mean serum Her-2/neu level was 13.6 ng/mL. Elevated serum Her-2/neu levels were seen in 71.7% of metastatic breast cancer samples. The serum Her-2/neu level correlated with expression of Her-2/neu in metastatic tissue as determined by IHC analysis (p<0.001) rather than with the Her-2/neu status of the primary breast cancer (p=0.16)

Conclusion

Serum Her-2/neu appears to be correlate with tissue Her-2/neu expression in primary and metastatic breast cancer where Her-2/neu is overexpressed. Further studies to determine levels of serum Her-2/neu are required to determine cuttoff values and the clinical application of the finding for breast cancer patients in Korea.

Keywords: Her-2/neu, Breast cancer, Immunohistochemisty

Figures and Tables

Fig 1

Distribution of serum Her-2/neu in primary breast cancer patients.

Fig 2

Distribution of serum Her-2/neu according to tissue Her-2/neu analysis (IHC) with grade 0/3 (n=117), grade 1/3 (n=44), grade 2/3 (n=33), and grade 3/3 (n=60). The means (SD) were as fellows: grade 0/3, 9.5 (1.7) ng/mL; grade 1/3, 9.3 (1.7) ng/mL; grade 2/3, 8.8 (1.6) ng/mL; grade 3/3, 12.3 (4.0) ng/mL. There was significant difference between groups (p<0.001).

Fig 3

ROC curve of serum Her-2/neu ECD concentration for differentiation of tissue Her-2/neu overexpression. AUC for serum Her-2/neu ECD was 0.73 (95% confidence interval; 0.66-0.80).

Fig 4

Serum Her-2/neu ECD concentration according to tissue Her-2/neu status in 18 patients with metastatic breast cancer with grade 0/3 (n=4), grade 1/3 (n=6), grade 2/3 (n=1), and grade 3/3 (n=8). The means (SD) were as follows: grade 0/3, 10.9 (1.8) ng/mL; grade 1/3, 11.13 (3.7) ng/mL; grade 2/3, 13.9 ng/mL; grade 3/3, 40.2 (16.1) ng/mL. There was significant difference between groups (p<0.001).

Table 1

Clinicopathologic finding of primary breast cancer

IHC=immunohistochemisty; FISH=fluroscent in situ hybridization; BCO=breast conserving operation; MRM=modified radical mastectomy; LN=lymph node; NOS=not otherwise specified.

Table 2

Correlation between serum Her-2/neu concentration and Her-2/neu status (IHC)

IHC=immunohistochemisty.

^*ANOVA test.

Table 3

Distribution of tissue Her-2/neu overexpression according to cuttoff value

Table 4

Correlation of serum Her-2/neu concentration and clinicopathologic variables

LN=lymph node; LVI=lymphovascular invasion; NG=nuclear grade; HG=histologic grade.

^*chi-square test; ^†ANOVA test.

Table 5

Correlation of Serum Her-2/neu concentration according to tumor subtype

SD=standard deviation; IDC=invasive ductal carcinoma; ILC=invasive lobular carcinoma.

Table 6

Comparison of Her-2/neu status (IHC) between primary breast cancer and metastatic site with serum Her-2/neu

IHC=immunohistochemistry; SCLN=supraclavicular lymph node; IMLN=internal mammary lymph node.

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