title: Diagnostic utility of novel stem cell markers SALL4, OCT4, NANOG, SOX2, UTF1, and TCL1 in primary mediastinal germ cell tumors.
abstract: Primary mediastinal germ cell tumors (GCTs) are rare and sometimes they pose diagnostic difficulty without immunohistochemical studies. Here, we investigated the diagnostic utility of 6 stem cell markers (SCMs) SALL4, OCT4, NANOG, SOX2, UTF1, and TCL1 in 16 primary mediastinal seminomas, 3 embryonal carcinomas (ECs), 10 yolk sac tumors (YSTs), 7 teratomas (4 mature, 3 immature), and 1 choriocarcinoma. The percentage of tumor cells stained was scored as: 0 (no tumor cell staining), 1+ (< or =30%), 2+ (31% to 60%), 3+ (61% to 90%), and 4+ (>90%). The staining intensity of SCMs was scored as weak, moderate, or strong. We also compared them with currently used GCT markers placental-like alkaline phosphatase (PLAP), alpha-fetoprotein (AFP), c-KIT, CD30, and glypican-3. All 16 seminomas showed staining for SALL4 (4+ in 15, 2+ in 1) (15 strong, 1 moderate), OCT4 (4+ in 11, 3+ in 4, 2+ in 1) (13 strong, 3 moderate), and UTF1 (4+ in 13, 3+ in 2, 2+ in 1) (7 strong, 5 moderate, 4 weak). Positive staining was shown by 9/9 seminomas tested for NANOG (4+ in 7, 2+ in 2) (8 strong, 1 weak), TCL1 (4+ strong in all), c-KIT (4+ in all), and PLAP (4+ in 5, 3+ in 1, 2+ in 2, 1+ in 1), but SOX2 staining was negative in all these tumors. All 3 ECs showed 4+ strong staining for SALL4, OCT4, and UTF1 but negative for TCL1. SOX2 staining was seen in 3/3 ECs (4+ strong in 1, 3+ weak to moderate in 2) whereas NANOG staining was seen in 2/3 ECs (2+ weak, 1+ moderate). CD30 staining was seen in 3/3 ECs (1+, 2+, 4+). Strong SALL4 staining was seen in 10/10 YSTs (4+ in 9, 2+ in 1). All 10 YSTs showed AFP (1+ in 7, 2+ in 1, 3+ in 2) and glypican-3 (1+ in 3, 2+ in 1, 3+ in 5, 4+ in 1) staining but only 4/10 YSTs showed PLAP staining (1+ in all 4). The mean percentage of YST cells stained with SALL4 was 92%, whereas it was 23% for AFP, 50% for glypican-3, and 4% for PLAP (P<0.01). Focal (1+) SALL4 (weak) and SOX2 (weak to moderate) staining was seen in 2/7 and 4/7 teratomas, respectively. The choriocarcinoma was negative for all 6 SCMs. Eleven thymomas and 6 thymic carcinomas were negative for 6 SCMs. No staining of NANOG and SOX2 was seen in 20 lymphomas (5 Hodgkin, 5 large B cell, 5 lymphoblastic, 5 anaplastic large cell) (other 4 SCMs in lymphomas earlier studied). Our study indicates that SALL4, OCT4, NANOG, SOX2, UTF1, and TLC1 are novel sensitive diagnostic markers for primary mediastinal GCTs, with high specificity. Of these 6 SCMs, SALL4 is the only 1 expressed in YST. These novel SCMs are more sensitive than the currently used markers for mediastinal GCTs.
authors.affiliation: Department of Pathology, The Chinese PLA General Hospital, Beijing Hospital, Beijing, China.
authors.forename: Aijun
authors.initials: A
authors.lastname: Liu
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
authors.forename: Jun
authors.initials: J
authors.lastname: Du
authors.forename: Yan
authors.initials: Y
authors.lastname: Peng
authors.forename: Robert W
authors.initials: RW
authors.lastname: Allan
authors.forename: Lixin
authors.initials: L
authors.lastname: Wei
authors.forename: Jianping
authors.initials: J
authors.lastname: Li
authors.forename: Dengfeng
authors.initials: D
authors.lastname: Cao
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008479:Mediastinal Neoplasms / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D000071317:Nanog Homeobox Protein; D009373:Neoplasms, Germ Cell and Embryonal / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D009687:Nuclear Proteins; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D011518:Proto-Oncogene Proteins; C472575:SALL4 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C090851:TCL1A protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C484738:UTF1 protein, human