J Breast Cancer.  2006 Dec;9(4):301-308. 10.4048/jbc.2006.9.4.301.

Establishment for Reference Range of Serum HER-2/neu in Korean Healthy Women

• Kim JW
• Kim SY
• Lee HS
• Woo HD
• Son DM
• Lim CW
• Choi TY
• Jang YS
• Kim JJ
• Lee MH

• KMID: 2286601
• DOI: http://doi.org/10.4048/jbc.2006.9.4.301

Abstract

PURPOSE: HER-2/neu oncogene is known to play a part in the process of carcinogenesis, while the biological characteristics of HER-2/neu oncoprotein include regulating cell growth and increasing the reproductionability of a tumor. The extracelluar domain (ECD), whose molecular weight is between 95 and 105 kD among the HER-2/neu oncoprotein structures, is proteolyzed and separated from the cell surface by metalloproteases and goes into the blood stream where it starts circulation. Since monoclonal antibody was developed for the serum HER-2/neu ECD, it's now possible to measure HER-2/neu ECD in the serum with the immunoassay method. The measurement of serum HER-2/neu ECD is used for prognosis of metastatic breast cancer and for testing the treating effect of trastuzumab (Herceptin(R)), a target agent for the patients positive to the HER-2/neu receptor. In Korea there is no report on the accurate reference range of serum HER-2/neu for healthy women. The purposes of this study were to measure the serum HER-2/neu ECD in healthy Korean women, analyze the reference range.
METHODS
The subjects of the study include 200 healthy Korean women with 50 from each in their twenties, thirties, forties, and fifties. As for methodology, the HER-2/neu in the serum separated from their blood was measured. The serum HER-2/neu level was measured quantitatively with the recently developed ADVIA Centaur(R) automated immunoassay analyzer and ADVIA Centaur(R) HER-2/neu assay reagent. With the measurement, you can use the sandwich immunoassay and direct chemiluminescence technique for two monoclonal antibodies for the epitopes located in the serum HER-2/neu ECD. The reference ranges were calculated based on the mean +/- 2 SD.
RESULTS
One of the 200 healthy subjects was excluded from analysis for having the highest value of serum HER-2/neu (23.1 ng/ml), and the data of total 199 were used for analysis. The analysis results indicated that the minimum value was 3.5 ng/mL, the maximum value 14.5 ng/mL, the mean 8.6 ng/mL, average 8.77 ng/mL, and SD 1.61 ng/mL. The reference range of the 199 subjects's serum HER-2/neu measurements was calculated by the mean +/- 2 SD. Since the mean +/- SD of their HER-2/neu measurements was 8.8 +/- 1.6 ng/mL, the reference range was 5.6~12.0 ng/mL. The reference ranges for the age groups were 6.1~10.9 ng/mL, 5.3~11.4 ng/mL, 5.0~12.6 ng/mL and 6.3~12.6 ng/mL for the twenties, thirties, forties and fifties, respectively. The reference ranges for the age groups were analyzed statistically and there was statistical difference (p= 0.002) between fifties and twenties or thirties. The upper limit level of the reference range of serum HER-2/neu in healthy Korean women was 12.0 ng/mL.
CONCLUSION
The results suggest that the reference range of serum HER-2/neu in healthy Korean women is 6.1~10.9 ng/mL, 5.3~11.4 ng/mL, 5.0~12.6 ng/mL and 6.3~12.6 ng/mL for the twenties, thirties, forties, and fifties, respectively. There is no significant difference between the twenties, thirties, forties, each other. According to analyzed statistically, there is difference between fifties and twenties or thirties (p= 0.002), but there is no statistically significant difference between forties and fifties.

Keyword

Serum HER-2/neu; Breast; Cancer; Reference range

MeSH Terms

Antibodies, Monoclonal
Breast
Breast Neoplasms
Carcinogenesis
Epitopes
Female
Humans
Immunoassay
Korea
Luminescence
Metalloproteases
Molecular Weight
Oncogenes
Population Characteristics
Prognosis
Reference Values*
Reproduction
Rivers
Trastuzumab
Antibodies, Monoclonal
Epitopes
Metalloproteases

Figure

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  Fig 1 Histogram of serum HER-2/neu in healthy Korean women

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  Fig 2 Distribution, mean and standard deviation according to age group of serum HER-2/neu in healthy Korean women

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