Oncopathology Research Center, Iran University of Medical Sciences (IUMS), Tehran, Iran.
Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
J Cancer Res Clin Oncol. 2022 Mar;148(3):609-631. doi: 10.1007/s00432-021-03859-1. Epub 2021 Nov 27.
Melanoma-associated antigen A2 (MAGE-A2) is a member of the cancer-testis antigen family differentially overexpressed in a variety of malignancies and is associated with tumor development. However, clinical significance and prognostic value of MAGE-A2 in different histological subtypes of testicular germ cell tumors (TGCTs) have not been explored.
Here, we aimed to investigate the clinical significance and prognostic impact of MAGE-A2 expression in TGCTs compared to benign tumors as well as adjacent normal tissues and then between seminomas and non-seminomas groups using immunohistochemistry on tissue microarrays.
The results indicated a statistically significant difference between overexpression of MAGE-A2 and histological subtypes of TGCTs. A statistically significant association was found between a high level of nuclear expression of MAGE-A2 protein and advanced pT stage (P = 0.022), vascular invasion (P = 0.037), as well as involvement of rete testis (P = 0.022) in embryonal carcinomas. Increased nuclear expression of MAGE-A2 was observed to be associated with more aggressive behaviors and tumor progression rather than cytoplasmic expression in these cases. Further, high level nuclear expression of MAGE-A2 had shorter disease-specific survival (DSS) or progression-free survival (PFS) compared to patients with moderate and low expression of MAGE-A2, however, without a statistically significant association.
Our results confirm that increased nuclear expression of MAGE-A2 has a clinical significance in embryonal carcinomas and is associated with progression of disease. Moreover, MAGE-A2 may act as a potential predictive biomarker for the prognosis in embryonal carcinomas if follow-up period becomes longer. Further investigations for the biological function of MAGE-A2 are required in future studies.
黑色素瘤相关抗原 A2(MAGE-A2)是一种癌症-睾丸抗原家族的成员,在多种恶性肿瘤中过度表达,与肿瘤的发生有关。然而,MAGE-A2 在不同组织学亚型的睾丸生殖细胞肿瘤(TGCT)中的临床意义和预后价值尚未得到探索。
在这里,我们旨在通过免疫组织化学方法在组织微阵列上研究 MAGE-A2 表达在 TGCT 与良性肿瘤以及相邻正常组织之间的临床意义和预后影响,然后在精原细胞瘤和非精原细胞瘤组之间进行比较。
结果表明,MAGE-A2 的过度表达与 TGCT 的组织学亚型之间存在统计学上的显著差异。MAGE-A2 蛋白核表达水平与高 pT 分期(P=0.022)、血管侵犯(P=0.037)以及胚胎癌的 rete testis 受累之间存在统计学显著相关性。在这些病例中,MAGE-A2 的核表达增加与更具侵袭性的行为和肿瘤进展有关,而与细胞质表达无关。此外,与 MAGE-A2 中度和低度表达的患者相比,高水平核表达的 MAGE-A2 患者的疾病特异性生存(DSS)或无进展生存(PFS)较短,但无统计学意义。
我们的结果证实,MAGE-A2 的核表达增加在胚胎癌中具有临床意义,并与疾病的进展有关。此外,如果随访时间延长,MAGE-A2 可能成为胚胎癌预后的潜在预测生物标志物。未来的研究需要进一步研究 MAGE-A2 的生物学功能。