Overexpression of MAGE-A9 predicts unfavorable outcome in breast cancer

Exp Mol Pathol. 2014 Dec;97(3):579-84. doi: 10.1016/j.yexmp.2014.11.001. Epub 2014 Nov 5.

Abstract

Melanoma-associated antigens (MAGEs) are a group of well-characterized members of the cancer/testis antigen (CTA) family, which is one of the largest groups of human tumor-associated antigens. MAGE-A9 is a particular member in the context of the MAGE-A gene family and was defined as presenting prognostic relevance in certain type of human cancer. However, the expression of MAGE-A9 in invasive ductal breast cancer (IDC) and the relationship with the clinical attributes of IDC, especially prognostic characteristic, remain poorly understood. In this present study, one-step quantitative reverse transcription polymerase chain reaction (18 fresh-frozen IDC tissues and corresponding non-cancerous tissues) and immunohistochemistry by tissue microarrays (82 IDC tissue samples and 70 matched tumor-adjacent non-cancerous tissue samples) were performed to characterize expression of the MAGE-A9 gene in IDC. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of IDC. The results of qPCR and IHC analysis showed that the expression of MAGE-A9 in IDC was significantly higher than that in corresponding non-cancerous tissue. Moreover, the expression level of MAGE-A9 protein in IDC was significantly related to histological grade (p = 0.011) and distant metastasis (p = 0.019). Multivariate analysis with the Cox regression model showed that MAGE-A9 protein expression (p = 0.009), histological grade (p = 0.014), lymph node metastasis (p = 0.012) and distant metastasis (p = 0.011) were independent prognostic factors for overall survival of IDC patients. The data suggest that MAGE-A9 expression is correlated with malignant attributes of IDC and it may serve as a novel prognostic factor and an ideal candidate for targeted therapy in IDC treatment.

Keywords: IDC; Immunohistochemistry; MAGE-A9; Prognosis; Tissue microarray; qPCR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / biosynthesis*
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / mortality
  • Carcinoma, Ductal, Breast / pathology*
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Proteins / biosynthesis*
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Array Analysis
  • Up-Regulation

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • MAGEA9 protein, human
  • Neoplasm Proteins