Expression and possible prognostic role of MAGE-A4, NY-ESO-1, and HER-2 antigens in women with relapsing invasive ductal breast cancer: retrospective immunohistochemical study

Abstract

Aim: To evaluate the possible prognostic role of the expression of MAGE-A4 and NY-ESO-1 cancer/testis antigens in women diagnosed with invasive ductal breast cancer and determine the expression of HER-2 antigen.

Methods: The expression of MAGE-A4, NY-ESO-1, and HER-2 antigens was evaluated immunohistochemically on archival paraffin-embedded samples of breast cancer tissue from 81 patients. All patients had T1 to T3, N0 to N1, M0 tumors and underwent postoperative radiotherapy and, if indicated, systemic therapy (chemotherapy and hormonal therapy). The antigen expression in women who were disease-free for 5 years of follow up (n=23) was compared with that in women with either locoregional relapse (n=30) or bone metastases (n=28). Patient survival after 10 years of follow up was assessed.

Results: The three groups of women were comparable in terms of age, type of operation, tumor size, tumor grade, number of metastatically involved axillary lymph nodes, Nottingham prognostic index (NPI), progesterone receptor (PR) status, and adjuvant hormonal therapy. Estrogen receptors (ER) were positive in 13 women in the 5-year relapse-free group vs 8 in locoregional relapse and 7 in bone metastases group (P=0.032). There were significantly fewer women who received adjuvant chemotherapy in the 5-year relapse-free group than in other two groups (7 vs 23 with locoregional relapse and 25 with bone metastases; P<0.001). This group also had a significantly better 10-year survival (14 women vs 1 with locoregional relapse and 1 with bone metastases; P<0.001). The three groups did not differ in the NY-ESO-1 or HER-2 expression, but the number of patients expressing MAGE-A4 antigen was significantly lower in the group with locoregional relapse (P=0.014). In all groups, MAGE-A4 antigen expression was associated with the NY-ESO-1 antigen expression (P=0.006), but not with tumor size and grade, number of metastatically involved axillary lymph nodes, or the ER and PR status. MAGE-A4-positive patients had a significantly longer survival than the MAGE-A4-negative patients (P=0.046). This was not observed with NY-ESO-1 and HER-2 antigens.

Conclusion: Our results suggest that the MAGE-A4 antigen may be used as a tumor marker of potential prognostic relevance.

Figure 1

Immunohistochemical staining in invasive ductal breast cancer tissue. A. Intense cytoplasmic MAGE-A4 staining with monoclonal antibody (mAb) 57B observed in the absence of staining of normal ducts (peroxidase anti-peroxidase [PAP], ×400). B. NY-ESO-1 positivity with specific cytoplasmic tumor distribution detected by mAb B9.8.1.1 (PAP, ×400). C. Overexpression of HER-2 detected by Hercep test, with strong complete membrane staining in >10% of tumor cells, noticed as a strong immunohistochemical reaction (PAP, ×400).

Figure 2

Overall survival of 81 women with invasive ductal breast cancer according to the MAGE-A4 expression. Full line – MAGE-A4 positive (1+, 2+, 3+) (n = 60); dotted line – MAGE-A4 negative (0) (n = 21); plus sign – censored data; circle – complete data. Gehan’s Wilcoxon test, P = 0.046.