Diagnostic utility of novel stem cell markers SALL4, OCT4, NANOG, SOX2, UTF1, and TCL1 in primary mediastinal germ cell tumors.
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.
Liu
Aijun
A
Department of Pathology, The Chinese PLA General Hospital, Beijing Hospital, Beijing, China.
Cheng
Liang
L
Du
Jun
J
Peng
Yan
Y
Allan
Robert W
RW
Wei
Lixin
L
Li
Jianping
J
Cao
Dengfeng
D
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
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