Reduced cytoplasmic expression of MAGE-A2 predicts tumor aggressiveness and survival: an immunohistochemical analysis

World J Urol. 2021 Jun;39(6):1831-1843. doi: 10.1007/s00345-020-03395-6. Epub 2020 Aug 9.

Abstract

Background: Melanoma antigen gene A2 (MAGE-A2) is one of the most cancer-testis antigens overexpressed in various types of cancers. Silencing the MAGE-A2 expression inhibited the proliferation of prostate cancer (PCa) cells and increased the chemosensitivity. However, the expression pattern of MAGE-A2 in PCa tissue samples and its prognostic and therapeutic values for PCa patients is still unclear.

Methods: In this study, for the first time, the staining pattern and clinical significance of MAGE-A2 were evaluated in 166 paraffin-embedded prostate tissues, including 148 cases of PCa and 18 cases of high-grade prostatic intraepithelial neoplasia (HPIN), by immunohistochemical analysis.

Results: The simultaneous expression of both nuclear and cytoplasmic patterns of MAGE-A2 with different staining intensities was observed among studied cases. Increased expression of MAGE-A2 was significantly found in PCa tissues compared to HPIN cases (P < 0.0001). Among PCa samples, the strong staining intensity of nuclear expression was predominantly observed in comparison with cytoplasmic expression in PCa tissues (P < 0.0001). A significant and inverse correlation was found between the cytoplasmic expression of MAGE-A2 and increased Gleason score (P = 0.002). Increased cytoplasmic expression of MAGE-A2 was associated with longer biochemical recurrence-free survival (BCR-FS) and disease-free survival (DFS) of patients (P = 0.002, P = 0.001, respectively). In multivariate analysis, Gleason score and cytoplasmic expression of MAGE-A2 were independent predictors of the BCR-FS (P = 0.014; P = 0.028, respectively).

Conclusions: Taken together, cytoplasmic expression of MAGE-A2 was inversely proportional to the malignant grade and duration of recurrence of the disease in patients with PCa.

Keywords: High-grade prostatic intraepithelial neoplasia (HPIN); Immunohistochemistry; MAGE-A2; Prostate cancer (PCa).

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cytoplasm
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Male
  • Melanoma-Specific Antigens / genetics*
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Prognosis
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / mortality*
  • Prostatic Neoplasms / pathology*
  • Survival Rate

Substances

  • MageA2 protein, human
  • Melanoma-Specific Antigens
  • Neoplasm Proteins