MAGE-A2 细胞质表达减少预示肿瘤侵袭性和生存：免疫组织化学分析。

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

机构信息

Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Hasheminejad Kidney Center, Iran University of Medical Sciences, Tehran, Iran.

出版信息

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

DOI:10.1007/s00345-020-03395-6

PMID:32772147

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.

摘要

背景

黑色素瘤相关抗原基因 A2（MAGE-A2）是在多种癌症中过度表达的最常见的癌-睾丸抗原之一。沉默 MAGE-A2 的表达可抑制前列腺癌（PCa）细胞的增殖，并增加化学敏感性。然而，MAGE-A2 在 PCa 组织样本中的表达模式及其对 PCa 患者的预后和治疗价值仍不清楚。

方法

本研究首次通过免疫组织化学分析，评估了 MAGE-A2 在 166 例石蜡包埋的前列腺组织中的染色模式及其临床意义，其中包括 148 例 PCa 和 18 例高级别前列腺上皮内瘤变（HPIN）。

结果

在所研究的病例中，观察到 MAGE-A2 的核和细胞质两种不同染色强度的同时表达。与 HPIN 病例相比，PCa 组织中 MAGE-A2 的表达增加（P<0.0001）。在 PCa 样本中，与细胞质表达相比，核表达的强染色强度在 PCa 组织中更为明显（P<0.0001）。MAGE-A2 的细胞质表达与增加的 Gleason 评分之间存在显著的负相关关系（P=0.002）。增加的 MAGE-A2 细胞质表达与患者更长的生化无复发生存期（BCR-FS）和无病生存期（DFS）相关（P=0.002，P=0.001）。在多变量分析中，Gleason 评分和 MAGE-A2 的细胞质表达是 BCR-FS 的独立预测因子（P=0.014；P=0.028）。