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

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 (P = 0.026) in seminomas. Whereas in embryonal carcinomas, cytoplasmic expression of SALL4-A was associated with the tumour recurrence (P = 0.04) and invasion of the epididymis (P = 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.

Keywords:

• Testicular cancer
• SALL4-A
• seminoma
• tissue microarray
• prognosis
• biomarker

Disclosure statement

No potential competing interest was reported by the authors.

Data availability statement

The data that support the findings of this study are available from the corresponding author, [Z.M], upon reasonable request.

Additional information

Funding

This work is part of a PhD thesis supported by Oncopathology Research Center of Iran University of Medical Sciences (Grant No.: 32223) and Avicenna Research Institute (Grant No: 960112-038).