Trials of new germ cell immunohistochemical stains in 93 extragonadal and metastatic germ cell tumors.
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-2gamma 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-2gamma 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-2gamma, 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.
Iczkowski
Kenneth A
KA
Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32608, USA. kenneth.iczkowski@uchsc.edu
Butler
Samantha L
SL
Shanks
Jonathan H
JH
Hossain
Deloar
D
Schall
Albrecht
A
Meiers
Isabelle
I
Zhou
Ming
M
Torkko
Kathleen C
KC
Kim
Stacy J
SJ
MacLennan
Gregory T
GT
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000032:analysis; D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D018237:Germinoma / Q000737:chemistry* / Q000556:secondary; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000032:analysis*; D050814:Octamer Transcription Factor-3 / Q000032:analysis; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000473:pathology; D012680:Sensitivity and Specificity; D013736:Testicular Neoplasms / Q000737:chemistry* / Q000473:pathology; D050656:Transcription Factor AP-2 / Q000032:analysis
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D050656:Transcription Factor AP-2; C500987:monoclonal antibody D2-40