Trials of new germ cell immunohistochemical stains in 93 extragonadal and metastatic germ cell tumors

Kenneth A. Iczkowski, Samantha L. Butler, Jonathan H. Shanks, Deloar Hossain, Albrecht Schall, Isabelle Meiers, Ming Zhou, Kathleen C. Torkko, Stacy J. Kim, Gregory T. MacLennan

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


Organic cation transporter 3/4 (OCT3/4) is a transcription factor of embryonic stem cells; c-kit (CD117) is a tyrosine kinase receptor implicated in seminoma carcinogenesis. Their reactivity is well characterized in testicular, but not extragonadal and metastatic, germ cell tumors. A total of 93 germ cell tumors (41 seminoma, 22 embryonal carcinoma, 18 teratoma, and 12 yolk sac tumor) were obtained from the central nervous system (30), mediastinum (23), retroperitoneum/abdomen (31), and other locations (9). Immunohistochemical staining for c-kit, placental-like alkaline phosphatase (PLAP), OCT3/4, and new markers D2-40 and AP-2γ was performed on seminomas; CD30 and epithelial membrane antigen were added for nonseminomas. In embryonal carcinoma, c-kit reacted in 17 of 22 cases, OCT3/4 in 18 of 22, and PLAP in 13 of 22. OCT3/4 was superior to PLAP in intensity and percent cells staining. In seminoma, OCT3/4 and D2-40 were superior to PLAP in intensity and percent cells; c-kit and AP-2γ were superior in percent cells. D2-40 stained 23 of 24 seminomas strongly but had only weak focal reactivity in 6 of 17 embryonal carcinomas. Sensitivity and specificity were high for OCT3/4 discriminating seminoma and embryonal carcinoma, and c-kit discriminating seminoma, from other germ cell tumors. For embryonal carcinoma, OCT3/4 had higher specificity (0.94) than CD30 (0.786) owing to CD30 reactivity in 3 of 10 teratomas. Epithelial membrane antigen discriminated teratoma from other nonseminomas with a sensitivity of 1 but reacted occasionally in embryonal carcinoma (3/15) and yolk sac tumor (2/7). In conclusion, for extragonadal seminoma, OCT3/4, AP-2γ, D2-40, and c-kit were equivalently superior to PLAP. For embryonal carcinoma, OCT3/4 was superior to PLAP and more specific than CD30. D2-40 is recommended to discriminate between seminoma and embryonal carcinoma.

Original languageEnglish (US)
Pages (from-to)275-281
Number of pages7
JournalHuman Pathology
Issue number2
StatePublished - Feb 2008


  • AP-2γ
  • D2-40
  • Extragonadal
  • Germ cell tumor
  • Mediastinum
  • OCT3/4
  • Pineal
  • c-kit

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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