SALL4 Is a Novel Sensitive and Specific Diagnostic Marker for Testicular Germ Cell Tumors
D Cao, RW Allan, PA Humphrey. Washington University in Saint Louis, Saint Louis; University of Florida, Gainesville, FL
Background: Most of testicular germ cell tumors (TGCTs) are malignant but they are curable with modern therapy. The diagnosis of TGCTs is usually straightforward but sometimes it can be challenging necessitating ancillary markers. Earlier markers such as AFP, PLAP, C-KIT and CD30 show only moderate sensitivity and specificity. Recently novel stem cell markers OCT4, NANOG and SOX2 have emerged as more sensitive and specific markers for certain TGCTs. More recently SALL4 has been identified as a new member in the family of OCT4, NANOG and SOX2. However, no study has investigated the utility of SALL4 as a potential diagnostic marker in TGCTs.
Design: Ninety-eight primary TGCTs were retrieved including 54 pure tumors (44 seminomas, 5 embryonal carcinomas (EC), 5 pure yolk sac tumors (YST)) and 44 mixed germ cell tumors (with seminoma in 18 cases, YST in 26 , EC in 34, teratoma in 24 including 5 with immature elements, and choriocarcinoma in 6). Fifty cases also contained intratubular germ cell neoplasia (ITGCN) for SALL4 staining. To test SALL4 specificity in testis, 10 Leydig cell tumors (LCT), 4 Sertoli cell tumors (SCT), 3 adenomatoid tumors, and 2 primary diffuse large B cell lymphomas (DLBCLs) were also stained. One to 2 formalin fixed paraffin embedded tissue blocks per case were used to prepare unstained slides for immunostain with a SALL4 monoclonal antibody. 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 tumor cell staining), 1+ (<=30% tumor cells), 2+ (31-60%), 3+ (61-90%), and 4+ (>90%).
Results: All 50 ITGCNS, 62 seminomas, 39 ECs, and 31 YSTs showed strong 4+ (>90% tumor cells) SALL4 staining. SALL4 staining was seen in the mononucleated trophoblastic cells in 6 of 6 choriocarcinomas (1+ weak in 1, 3+ strong in 3, 4+ strong in 2). Syncytiotrophoblastic cells in choriocarcinomas and in other TGCTs were negative for SALL4 staining. The teratomatous glands in 22 of 24 teratomas showed 1+ weak SALL4 staining. The immature elements showed 1+ weak SALL4 staining in 4 of 5 cases. In contrast, no SALL4 staining was seen in all LCTs, SCTs, adenomatoid tumors and DLBCLs. The only non-neoplastic cells within the testis stained with SALL4 were spermatogonia (weak staining).
Conclusions: SALL4 is a novel sensitive and specific marker for TGCTs and should be included in the diagnostic panel in difficult cases.
Category: Genitourinary (including renal tumors)
Monday, March 9, 2009 1:00 PM
Poster Session II # 95, Monday Afternoon