Nature: Zing finger protein, transcription factor for maintenance of pluripotency, encoded by chromosome 20q13.
Function and occurrence: SALL4 is expressed in germ cells and fetal gut cells. It is a master regulator of embryonal pluripotency together with the other pluripotency-related transcription factors such as OCT4 and NANOG.
+ SALL4 is consistently expressed in germ cell tumors (except some trophoblast tumours). In seminoma, embryonal carcinoma and yolk sac tumour, the expression is strong and uniform. In teratomas, SALL4 may be expressed in intestinal-like and squamous epithelia. Intratubular germ cell neoplasia (ITGCN) and spermatocytic seminomas are generally positive. Hepatoid carcinoma in e.g., stomach is generally positive.
+/- SALL4 is expressed in most cases rhabdoid tumors of the kidney and extrarenal sites and in the Wilms tumor.
-/+ SALL4 is less frequently expressed in serous carcinoma of the ovary (30%), urothelial high-grade carcinoma (20%), and tubular gastric adenocarcinoma.
-(+) SALL4 is rarely expressed in mammary, lung, colorectal, pancreatic, prostatic, endometrioid and squamous cell carcinomas, particularly those showing poorly differentiated patterns. SALL4 has also been detected in few cases of rhabdoid tumour, malignant melanoma, desmoplastic small round cell tumor, epithelioid sarcoma, and rhabdomyosarcoma.
- SALL4 is not expressed in sarcomas (apart from the above mentioned) and haematolymphoid neoplasms.
SALL4 is a highly sensitive marker for germ cell tumours but as it is not entirely specific, SALL4 should be used in panels with e.g., OCT4 and NANOG.
Normal testis is recommended as positive tissue control for SALL4. The majority of spermatogonia lining the basement membrane in seminiferous tubules must show an at least weak to moderate but distinct nuclear staining reaction. A dot-like staining of nucleoli in dispersed spermatocytes may be seen. No staining of stromal cells, including Leydig cells, should be seen. Appendix can be used as negative tissue control. No staining reaction should be seen.
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