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SALL4-A 异构体的高表达与特定类型睾丸生殖细胞肿瘤的不良预后和疾病进展相关。

Higher expression of SALL4-A isoform is correlated with worse outcomes and progression of the disease in subtype of testicular germ cell tumours.

机构信息

Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran.

Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.

出版信息

Biomarkers. 2024 Jul;29(5):324-339. doi: 10.1080/1354750X.2024.2361796. Epub 2024 Jun 5.

DOI:10.1080/1354750X.2024.2361796
PMID:38808385
Abstract

BACKGROUND

The transcription factor SALL4 is associated with embryonic pluripotency and has proposed as a novel immunohistochemistry (IHC) marker for diagnosing germ cell tumours. SALL4 comprises three isoforms, and SALL4-A being the full-length isoform. Studying its isoforms could revolutionize testicular cancer prognosis and subtype differentiation.

METHODS

The expression and clinical significance of isoform 'A' of SALL4 was evaluated in 124 testicular germ cell tumours (TGCTs) subtypes, adjacent 67 normal tissues and 22 benign tumours, using immunohistochemistry on tissue microarrays (TMA).

RESULTS

A statistically significant higher expression of nuclear and cytoplasmic SALL4-A was detected in TGCTs histological subtypes and benign tumours compared to the normal tissues. Seminoma and yolk sac tumours had the highest nuclear and cytoplasmic expression of SALL4-A. A significant correlation was detected between the higher nuclear expression of SALL4-A and increased pT stages ( = 0.026) in seminomas. Whereas in embryonal carcinomas, cytoplasmic expression of SALL4-A was associated with the tumour recurrence ( = 0.04) and invasion of the epididymis ( = 0.011).

CONCLUSIONS

SALL4-A isoform expression in the cytoplasm and nucleus of TGCTs may be associated with histological differentiation. In the seminoma subtype of TGCTs, higher expression of SALL4-A may be used as a predictive indicator of poorer outcomes and prognosis.

摘要

背景

转录因子 SALL4 与胚胎多能性有关,被提议作为诊断生殖细胞肿瘤的新型免疫组织化学(IHC)标志物。SALL4 包含三个同工型,SALL4-A 是全长同工型。研究其同工型可能会彻底改变睾丸癌的预后和亚型分化。

方法

使用组织微阵列(TMA)上的免疫组织化学方法,评估了 SALL4 同工型“A”在 124 种睾丸生殖细胞肿瘤(TGCT)亚型、相邻的 67 种正常组织和 22 种良性肿瘤中的表达及其临床意义。

结果

与正常组织相比,在 TGCT 组织学亚型和良性肿瘤中检测到核和细胞质 SALL4-A 的表达显著升高。精原细胞瘤和卵黄囊瘤具有最高的核和细胞质 SALL4-A 表达。在精原细胞瘤中,SALL4-A 的核高表达与 pT 分期升高显著相关( = 0.026)。而在胚胎癌中,细胞质 SALL4-A 的表达与肿瘤复发( = 0.04)和附睾浸润( = 0.011)相关。

结论

TGCT 中 SALL4-A 同工型在细胞质和细胞核中的表达可能与组织学分化有关。在 TGCT 的精原细胞瘤亚型中,SALL4-A 的高表达可能被用作预后较差的预测指标。

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