Establishing a germ cell origin for metastatic tumors using OCT4 immunohistochemistry

Cancer. 2004 Nov 1;101(9):2006-10. doi: 10.1002/cncr.20566.


Background: There are diverse morphologic manifestations of metastatic tumors. The determination of tumor origin is critical for patient management, and it is especially important when the differential diagnosis includes metastatic germ cell tumor, which is a highly treatable condition. OCT4 is a nuclear transcription factor that is expressed in pluripotent embryonic germ cells. In this study, the author sought to determine the usefulness of OCT4 immunohistochemistry in the diagnosis of metastatic germ cell tumors.

Methods: Sixty-two retroperitoneal lymph node dissection specimens from patients with histories of testicular germ cell tumors were stained using the antibodies against OCT4. In addition, 84 metastatic, nongerm cell lesions from men with known primary tumors were studied in parallel for OCT4 immunohistochemistry.

Results: All embryonal carcinoma components (n = 29 specimens) and seminoma components (n = 18 specimens) from retroperitoneal lymph node dissection specimens showed strong, intense, diffuse nuclear staining for OCT4. Yolk sac tumors (n = 12 tumors), choriocarcinomas (n = 4 tumors), mature teratomas (n = 16 tumors), and primitive neuroectodermal tumors (n = 5 tumors) were negative for OCT4 staining. Metastatic, nonsmall cell carcinomas from the lung (n = 14 tumors), colon (n = 12 tumors), stomach (n = 5 tumors), pancreas (n = 7 tumors), prostate (n = 12 tumors), kidney (n = 3 tumors), and urinary bladder (n = 15 tumors) all were found to be negative immunohistochemically for OCT4, as were metastatic small cell carcinomas (n = 4 tumors) and metastatic melanomas (n = 7 tumors). In addition, malignant lymphomas (n = 5 tumors) also were negative for OCT4.

Conclusions: Immunohistochemical detection of OCT4 is highly sensitive and specific for the diagnosis of seminoma and embryonal carcinoma metastatic from the testis. Establishing germ cell origin for metastatic tumors has important implications for assessing patient prognosis and treatment options.

MeSH terms

  • Biomarkers, Tumor / analysis*
  • DNA-Binding Proteins / analysis*
  • Germinoma / chemistry*
  • Germinoma / diagnosis
  • Germinoma / secondary
  • Humans
  • Immunohistochemistry
  • Ki-1 Antigen / analysis
  • Male
  • Octamer Transcription Factor-3
  • Testicular Neoplasms / chemistry*
  • Testicular Neoplasms / diagnosis
  • Transcription Factors / analysis*


  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Ki-1 Antigen
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • Transcription Factors