Clinical Significance of HER2/neu Gene Quantification and MAGE assay in Primary Breast Cancer

Lee, Nan Young; Park, Ho Yong; Lee, Young Ha; Suh, Jang Soo

Abstract

BACKGROUND
Many studies have reported that the HER2/neu gene and melanoma antigen gene (MAGE) are correlated with the progression and the prognosis of primary breast cancer (PBC). Since anti-HER2/neu monoclonal antibodies were introduced for an adjuvant treatment for PBC, the needs for the assessment of the HER2/neu status have been increased. Accordingly, we compared two methods evaluating HER2/neu status, and performed MAGE assay simultaneously. In addition, we also investigated the association of HER2/neu and MAGE with known disease parameters, and their clinical significance in PBC patients. METHODS: In 50 patients with PBC, HER2/neu protein and HER2/neu gene expression were assessed by immunohistochemical stain (IHC) and real-time quantitative polymerase chain reaction (Rt- Q-PCR), while MAGE expression was assessed by reverse transcriptase (RT)-nested PCR. RESULTS: The HER2/neu protein overexpression and overamplification were noted in 68.0% (34/50) and in 68.1% (32/47) of the patients, respectively. The concordance rate between these two methods was 61.7% (29/47) and the kappa value by analysis of reproducibility was as low as 0.086. HER2/neu protein overexpression was significantly correlated with P53 expression. HER2/neu overamplification was significantly correlated with histologic grades and inversely correlated with estrogen receptor (ER) expression (P=0.033). MAGE was expressed in 46.9% (23/49) in the current study. MAGE expression was shown to be significantly correlated with HER2/neu gene amplification (P=0.002), histological grades and P53 expression, and inversely correlated with ER expression (P=0.014). CONCLUSIONS: The current study revealed that the concordance between IHC and Rt-Q-PCR for HER2/neu evaluation was low in PBC. MAGE expression was significantly correlated with HER2/neu gene amplification and also associated with some clinical prognostic factors. So it is considered that MAGE expression has more important clinical prognostic significance than HER2/neu expression.