SALL4 Is a Novel Sensitive and Specific Marker for Metastatic Yolk Sac Tumor and Other Germ Cell Tumors
D Cao, PA Humphrey, RW Allan. Washington University in Saint Louis, Saint Louis, MO; University of Florida, Gainesville, FL
Background: Metastatic germ cell tumors (MGCTs) from testis, ovary and extragonadal sites are rare. Correct diagnosis is critical because MGCTs can be effectively treated and even cured with modern therapy. The correct diagnosis can sometimes be challenging without ancillary markers. Previous makers such as PLAP, AFP, C-Kit and CD30 only show moderate sensitivity and specificity. Recently stem cell markers OCT4, NANOG and SOX2 have emerged as more sensitive and specific markers for MGCTs. More recently SALL4 has been identified as a novel stem cell marker in the family of OCT4, NANOG and SOX2. The goal of this study is to investigate the utility of SALL4 as a potential diagnostic marker for MGCTs.
Design: Ninety-one MGCTs from testis (75), ovary (13) and extragonadal sites (3) were retrieved including 22 seminomas, 7 dysgerminomas, 22 embryonal carcinomas (EC), and 15 yolk sac tumors (YSTs), 7 choriocarcinomas and 18 teratomas. Unstained slides prepared from 1 to 2 paraffin blocks from each case were stained with a SALL4 monoclonal antibody. To test SALL4 specificity, 170 metastatic non-germ cell malignancies (6 head and neck carcinomas (CAs), 8 thyroid CAs, 12 lung CAs, 8 breast CAs, 7 hepatocellular CAs, 3 cholangiocarcinoma, 2 ampullary adenocarcinomas, 10 pancreatic adenocarcinomas, 18 gastric adenocarcinomas, 15 esophageal CA, 10 renal cell CAs, 10 urothelial CAs, 12 prostatic adenocarcinomas, 18 ovarian CAs, 6 uterine CAs, 13 colonic adenocarcinomas, and 12 melanomas) were also stained. Only nuclear staining was counted as positive. The staining intensity was scored as weak or strong. The percentage of tumor cells stained was scored semiquantitatively as: 0 (no cell staining), 1+ (<=30% cells), 2+ (31-60%), 3+ (61-90%), and 4+ (>90%).
Results: All 22 seminomas, 7 dysgerminomas, 22 ECs, and 15 YSTs showed strong 4+ (>90% tumor cells) positive for SALL4. Weak to strong SALL4 staining was seen in the mononucleated trophoblasts in 5/7 choriocarcinomas (1+ in 3, 3+ in 2); no SALL4 staining was seen in syncytiotrophoblastic cells (0/7). Nine of 17 teratomas showed 1+ positive SALL4 staining in teratomatous glands (weak) and immature elements (weak to focal strong). In contrast, only 10 (5 esophageal, 4 gastric, and 1 colonic CAs) of 170 metastatic somatic tumors showed focal 1+ weak SALL4 staining.
Conclusions: SALL4 is a novel sensitive and specific diagnostic marker for metastatic YST and other germ cell tumors.
Category: Genitourinary (including renal tumors)
Monday, March 9, 2009 11:30 AM
Platform Session: Section A, Monday Morning