SALL4 is a novel sensitive and specific marker for metastatic germ cell tumors, with particular utility in detection of metastatic yolk sac tumors.
BACKGROUND
The correct diagnosis of metastatic germ cell tumors is critical, because these tumors can be effectively treated and are even cured with modern therapy. Their histopathologic diagnosis can be challenging without immunohistochemical markers, which currently have limitations. SALL4 is a novel stem cell marker essential to maintain pluripotency and self-renewal of embryonic stem cells. In the current study, the authors investigated the utility of SALL4 as a potential diagnostic marker for metastatic germ cell tumors.


METHODS
Ninety metastatic germ cell tumors from testis, ovary, and extragonadal sites were stained with a monoclonal SALL4 antibody. In addition, 170 metastatic nongerm cell malignancies, including 158 carcinomas (6 head and neck, 8 thyroid, 12 lung, 8 breast, 7 hepatocellular, 3 cholangiocarcinomas, 2 ampullary, 10 pancreatic, 18 gastric, 15 esophageal, 10 renal cell, 10 urothelial, 12 prostatic, 18 ovarian, 6 uterine, and 13 colonic) and 12 melanomas, were also stained to test SALL4 specificity.


RESULTS
All 22 seminomas, 7 dysgerminomas, 22 embryonal carcinomas, and 14 of 15 yolk sac tumors displayed strong and diffuse SALL positivity in >90% of tumor cells (80% of tumor cells were strongly positive in the remaining yolk sac tumor). Five of 7 choriocarcinomas and 9 of 18 teratomas were also variably positive for SALL4. In contrast, only 10 (esophageal, gastric, and colonic adenocarcinomas) of 170 metastatic somatic tumors demonstrated focally weak SALL4 reactivity (<25% tumor cells).


CONCLUSIONS
SALL4 is a novel sensitive and highly specific marker for metastatic germ cell tumors, and is particularly useful for detecting metastatic yolk sac tumors.
Cao
Dengfeng
D
The Lauren V. Ackerman Laboratory of Surgical Pathology, Division of Anatomic and Molecular Pathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. dcao@path.wustl.edu
Humphrey
Peter A
PA
Allan
Robert W
RW
D014408:Biomarkers, Tumor / Q000032:analysis*; D018240:Endodermal Sinus Tumor / Q000175:diagnosis / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009362:Neoplasm Metastasis / Q000175:diagnosis*; D009373:Neoplasms, Germ Cell and Embryonal / Q000175:diagnosis* / Q000473:pathology; D050814:Octamer Transcription Factor-3 / Q000032:analysis; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000473:pathology; D013736:Testicular Neoplasms / Q000175:diagnosis* / Q000473:pathology; D014157:Transcription Factors / Q000032:analysis*
D014408:Biomarkers, Tumor; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C472575:SALL4 protein, human; D014157:Transcription Factors