OCT4 (POU5F1, OTF3, OCT3)

OCT4 is a POU-domain transcription factor. It is present on chromosome 6p21.3. Oct4 maintains pluropotentiality. It is detectable in embryonic stem and germ cells but downregulated in all differentiated somatic cell types5. It binds transcription sites through octamer motifs, including that for fibroblast growth factor 4 and platelet-derived growth factor a receptor3. Knockout of the gene is lethal in mice2. Staining is nuclear.

Immunohistochemical expression

Undifferentiated pluripotent cells
Germ cells of the ovary and testis, but not resting oocytes. It is not expressed by brain, heart, liver, spleen, skeletal muscle, lung, kidney or pancreas4.
Germ cell tumours:

Testicular tumours		OCT4
Carcinoma in situ		positive2
Mixed germ cell tumour (64 cases1), containing various combinations of components	seminoma	51/51(all showed strong (3+) staining)1, 49/492
	embryonal carcinoma	54/541, positive2
	yolk sac tumour	0/381, negative2
	mature teratoma	0/311, negative2
	immature teratoma	0/201, negative2
	choriocarcinoma	0/151, negative2
Spermatocytic seminoma		0/51, negative2
Leydig cell tumour		0/81
Sertoli cell tumour		0/61
Unclassified sex cord stromal tumour		0/41
Adenomatoid tumour		0/21
Testicular tumour of adrenogenital syndrome		0/11
Granulosa cell tumour		0/11
Ovarian tumours
Germ cell tumour	Ovarian dysgerminoma	2/22, 35/34
	Gonadoblastoma	1/12, 2/24
	Mature teratoma	0/144
	Yolk sac tumour	0/44
	Embryonal carcinoma	no data4
Leydig cell tumour		0/14
Sertoli cell tumour		0/14
Sertoli-Leydig cell tumour		0/134
Granulosa cell tumour	Adult type	0/134
Granulosa cell tumour	Juvenile type	0/94
Brenner tumour		0/34
Carcinoid tumour		0/44
Struma ovarii		0/24
Fibroma		0/54
Thecoma		0/14
Clear cell adenocarcinoma		4/144
Serous adenocarcinoma		0/54
Endometrioid adenocarcinoma		0/44
Small cell carcinoma, hypercalcaemic type		0/64
Stromal sarcoma		0/14
Lymphoma	Diffuse large B-cell type	0/24
	Burkitt's	0/34
	Small cleaved B-cell type	0/14
Metastatic malignant melanoma		0/14
Metastatic carcinoid		0/24
Metastatic small cell carcinoma		0/14
Metastatic lobular carcinoma of the breast		0/14
Non-gonadal tumours
CNS	germinoma	25/255
	glioblastoma multiforme	0/105
	lymphoma	0/45
	pineoblastoma	0/35
	metastatic malignant melanoma	0/45
	capillary haemangioma	0/105
	pituitary adenoma	0/55
	meningioma	0/45
	Schwannoma	0/45
	metastatic carcinoma	0/5(2 lung, 2 colon, 1 breast)5
non-testicular tumour microarray of 3439 tumours2, all non-gonadal tumours negative, except:	Pulmonary squamous cell carcinoma	1/502
	Pulmonary large cell carcinoma	1/472
	Renal clear cell carcinoma	1/502

Diagnostic utility

diagnosis of seminoma (including mediastinal seminoma), CNS germinoma, ovarian dysgerminoma4 and embryonal carcinoma.
- the ovarian tumours that form the differential for dysgerminoma are negative. Clear cell carcinoma may be positive, but occurs in older women.
possibly in the differentiation of ovarian clear cell carcinoma from yolk sac tumour, endometrioid of serous carcinoma4.
identification of a germ cell element, differentiating gonadoblastoma from pure sex cord stromal tumours.
identification of early testicular germ cell tumours6.

References

1 Jones, T. D., T. M. Ulbright, et al. (2004). "OCT4 Staining in Testicular Tumors: A Sensitive and Specific Marker for Seminoma and Embryonal Carcinoma." Am J Surg Pathol 28(7): 935-40.

2 Looijenga, L. H., H. Stoop, et al. (2003). "POU5F1 (OCT3/4) identifies cells with pluripotent potential in human germ cell tumors." Cancer Res 63(9): 2244-50. FULL TEXT AVAILABLE ON LINE.

3 Palumbo, C., K. van Roozendaal, et al. (2002). "Expression of the PDGF alpha-receptor 1.5 kb transcript, OCT-4, and c-KIT in human normal and malignant tissues. Implications for the early diagnosis of testicular germ cell tumours and for our understanding of regulatory mechanisms." J Pathol 196(4): 467-77.

4 Cheng, L., A. Thomas, et al. (2004). "OCT4: a novel biomarker for dysgerminoma of the ovary." Am J Surg Pathol 28(10): 1341-6.

5 Hattab EM, Tu PH, Wilson JD,Cheng L OCT4 Immunohistochemistry Is Superior to Placental Alkaline Phosphatase (PLAP) in the Diagnosis of Central Nervous System Germinoma. Am J Surg Pathol 2005; 29:368-371

6 Jones TD, MacLennan GT, Bonnin JM, et al. Screening for intratubular germ cell neoplasia of the testis using OCT4 immunohistochemistry. Am J Surg Pathol 2006; 30:1427-31

This page last revised 4.1.2007.