Different Roles of SALL4 and OCT3/4 in the Development and Evolving Processes of Benign and Malignant Germ Cells

Document Type

Conference Proceeding

Publication Date

6-2026

Publication Title

Journal of Clinical Oncology

Abstract

Background: In gonadogenesis, OCT3/4 and SALL4 are expressed in early germ cells and are critical for maintaining their pluripotency by suppressing differentiation. It is important to understand the variable expression of these two biomarkers throughout different stages of embryonic development as well as in tumor development. The primary aim of this study was to analyze SALL4 and OCT3/4 nuclear expression in various stages of fetal testes and examine their potential link to the risk of cryptorchidism in relation to later testicular tumor development. The second aim was to investigate the different expression patterns of SALL4 and OCT3/4 in metastatic germ cell tumors (GCT). Methods: Surgical and autopsy fetal testes ranging from 10 weeks of gestation to 11 months (n=10) were immunochemically stained for SALL4 and OCT3/ 4. OCT3/4 and SALL4 immunostains were further tested in 12 specimens from 11 patients with metastatic GCT. Results: SALL4 expression was maintained from early gonadogenesis within germ cells and persists regardless of age or malignant transformation. Whereas OCT3/4 expression started to diminish midway through the 3rd trimester. Expression of OCT3/4 was retained in a case of a cryptorchid testicle, suggesting that continued expression of OCT3/4 may be linked to an increased risk of GCT in individuals with cryptorchid testicles. OCT3/4 expression returned in germ cell neoplasia in situ and undifferentiated GCTs such as seminoma and embryonal carcinoma. Only 2/12 (17%) metastatic GCT were positive for both SALL4 and OCT3/ 4, but the majority of metastatic GCT (83% 10/12 cases) continued to evolve by losing expressions of OCT3/4 and maintaining expression of SALL4 (Table 1). Conclusions: Our data demonstrates bridging associations from OCT3/4 and SALL4 expressions in embryonal testis development to their presence in metastatic GCT, indicating a continuous evolving process from benign germ cells to malignant GCT. SALL4 is an important marker for identifying GCT in metastatic sites, whereas metastatic GCTs often lose OCT3/4 expression during progression.

Volume

44

Issue

16 Suppl

First Page

e17006

Last Page

e17006

Comments

American Society of Clinical Oncology (ASCO) Annual Meeting, May 29- June 2, 206, Chicago, IL

DOI

10.1200/JCO.2026.44.16_suppl.e17006

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