OCT4

Synonyms: POU5F1, OCT3, OCT3/4, OTF3

by Jan Klos

Background

OCT4 (octamer-binding transcription factor 4) is mapped to chromosome 6p21.3 coded by POU5F1. It is a protein involved in regulating many downstream target genes involved in maintaining of pluripotency of the cells. It is present in pluripotent undifferentiated cells including embryonic stem cells and germ cells. The protein is downregulated upon differentiation/maturation of cells.

Staining in normal cells

Embryonic germ cells are positive between 17 -37 week of gestation.

Staining in tumors

Positive in ITGCN, seminoma/dysgerminoma/ CNS germinoma, embryonal carcinoma, gonadoblastoma also when present as a component of mixed germ cell tumors but negative in yolk sac tumor (endodermal sinus tumor), choriocarcinoma, spermatocytic seminoma, teratomas and most of non-germinal cell malignancies. Majority of cases of clear cell carcinoma of the ovary, mucoepidermoid carcinoma, cholangiocarcinoma show also positive staining. Many cases of medullary carcinoma of kidney, colorectal carcinoma, squamous cell carcinoma of uterine cervix and breast carcinoma are also reported positive. Few cases of clear cell carcinoma of kidney and NSCLC as well as single cases of other tumors are also reported positive. All may be a source of potential diagnostic pitfall.

Staining pattern

Staining pattern is nuclear usually strong to moderate intensity in tumor cells with weak, sometimes dot-like staining in the cytoplasm.

Control tissue

Control tissue testis with positive germ cell tumor.

Application

  • Highly sensitive and quite specific positive marker of gonadal and extragonadal germ cell tumors (in situ, seminoma/dysgerminoma/ germinoma of CNS, gonadoblastoma and embryonal carcinoma)
  • Reported as more sensitive than CD30 in cases of embryonal carcinoma, especially after chemotherapy since chemotherapy is associated with frequent loss of CD30 reactivity
  • Considered more sensitive and specific than PLAP in these tumor types
  • The staining is negative in cases of yolk sac tumor but in combination with positive staining for SALL4 may support the diagnosis of these tumors
  • Be aware of possibility of positive reaction in non-germ cell tumors

Selected references

  1. Cheng L. Establishing a germ cell origin for metastatic tumors using OCT4 immunohistochemistry. Cancer 2004;101(9):2006-10.
  2. Hattab EM, Tu PH, Wilson JD et al. OCT4 immunohistochemistry is superior to placental alkaline phosphatase (PLAP) in the diagnosis of central nervous system germinoma. Am J Surg Pathol 2005;29(3):368-71.
  3. Honecker F, Stoop H, Mayer F, et al. Germ cell lineage differentiation in non-seminomatous germ cell tumours. J.Pathol. 2006;208(3):395-400.
  4. Jones TD, Ulbright TM, Eble JN et al. OCT4 staining in testicular tumors: a sensitive and specific marker for seminoma and embryonal carcinoma. Am J Surg Pathol. 2004;28(7):936-40.
  5. Looijenga LH, Stoop H, de Leeuw HP et al. POU5F1 (OCT3/4) identifies cells with pluripotent potential in human germ cell tumors. Cancer Res. 2003;63:2244-50.
  6. Sung MT, Jones TD, Beck SD et al. OCT4 is superior to CD30 in the diagnosis of metastatic embryonal carcinomas after chemotherapy. Hum Pathol. 2006 Jun;37(6):662-7.
  7. Williams AS, Shawwa A, Merrimen J et al. Expression of OCT4 and SALL4 in Diffuse Large B-cell Lymphoma: An Analysis of 145 Consecutive Cases and Testicular Lymphomas. Am J Surg Pathol. 2016 Jul;40(7):950-7.